Genetic Disorders and My Battle With EDS & CMT

Guestpost: W3Clinic is your online health and medication information center

noreply@blogger.com (Dallas Banks) — Mon, 23 Jan 2012 20:19:00 +0000

Some of us cannot afford a doctor's high fees they charge these days. And the environment not getting any better, the frequency with which we get sick is more than before. So in these dire times, how can we remain healthy without spending much of our hard earned money and still be getting the same quality of treatment. Something that can give all this, at one place, without any loopholes, it will certainly be a blessing for anyone and everyone.

W3Clinic is one such website that is a collection of all medicines and drugs, and health conditions. It contains a list of all the drugs present in the market and how to use them along with the side effects it can cause. Moreover, it gives complete information of a particular health condition or disease telling about all the precautions one can take to prevent it and what to do in case one finds oneself suffering from it. It gives home remedies as well as medicinal articles by professionals.

W3Clinic has created an organization that we believe fulfills the promise of health information on the Internet. We provide credible information, supportive communities, and in-depth reference material about health subjects that matter to you. We are a source for original and timely health information as well as material from well known content providers.

He continued, We pride ourselves in knowing our audience's needs and delivering the most appropriate experience. We know that there is a difference between using a health site for health performance" issues (e.g., flat abs) vs. health research needs (e.g., "What is type 2 diabetes?") vs. community support (e.g., "Does anyone else feel like me?") vs. e-commerce. Our mission is to fulfill all these needs in the most appropriate ways possible. We are committed to improving our site. We will continue to publish even more content, communities, and services to help make your life better, to help you find your way when faced with healthcare decisions, and to help you feel better about the health of you and your family.

W3Clinic is an upcoming website and might not be as famous as some other existing ones that are similar, but if they keep working with the same dedication and introduce some innovative ideas, it might become a great website.

Visit - http://www.w3clinic.com

Regards,

Edward

Health Website

noreply@blogger.com (Dallas Banks) — Mon, 16 Jan 2012 22:00:00 +0000

Recently, I received an email from someone that frequents my site about an informative health website he found. I reviewed the site, and it does have a lot of really good information, ranging from diseases/conditions to medications/treatments. I'll post the body of the email so you all will know more about it. I will also add it to my links page, so check it out sometime!

"W3Clinic is an online, healthcare information center produced by a team of Web professionals and medical experts. It provides easy-to-read, in-depth, authoritative medical information for consumers via its user-friendly and interactive website.

W3clinic provides the most detailed and credible information on a wide range of health topics, drugs and medications and medical conditions so as to help you feel better about the health of you and your family.

You can read more about it at http://www.w3clinic.com/about-us"

Chromosome II

noreply@blogger.com (Dallas Banks) — Mon, 16 Jan 2012 21:57:00 +0000

What is chromosome II?
Chromosome 2 is the second largest human chromosome, spanning more than 243 million building blocks of DNA (base pairs) and representing almost 8 percent of the total DNA in cells. Chromosome II likeley contains between 1,300 and 1,400 genes.

How are changes in chromosome II related to health problems?

cancers

Changes in chromosome 2 have been identified in several types of cancer. These genetic changes are somatic, which means they are acquired during a person's lifetime and are present only in certain cells. For example, a rearrangement (translocation) of genetic material between chromosomes 2 and 3 has been associated with cancers of a certain type of blood cell originating in the bone marrow (myeloid malignancies).

Trisomy 2, in which cells have three copies of chromosome 2 instead of the usual two copies, has been found in myelodysplastic syndrome. This disease affects the blood and bone marrow. People with myelodysplastic syndrome have a low number of red blood cells (anemia) and an increased risk of developing a form of blood cancer known as acute myeloid leukemia.

2q37 deletion syndrome

2q37 deletion syndrome is caused by a deletion of genetic material from a specific region in the long (q) arm of chromosome 2. The deletion occurs near the end of the chromosome at a location designated 2q37. The size of the deletion varies among affected individuals. The signs and symptoms of this disorder, which may include intellectual disability, autism, short stature, obesity, and characteristic facial features, are probably related to the loss of multiple genes in this region.

other chromosomal conditions

Another chromosome 2 abnormality is known as a ring chromosome 2. A ring chromosome is formed when breaks occur at both ends of the chromosome and the broken ends join together to form a circular structure. Individuals with this chromosome abnormality often have developmental delay, small head size (microcephaly), slow growth before and after birth, heart defects, and distinctive facial features. The severity of symptoms typically depends on how many and which types of cells contain the ring chromosome 2.

Other changes involving the number or structure of chromosome 2 include an extra piece of the chromosome in each cell (partial trisomy 2) or a missing segment of the chromosome in each cell (partial monosomy 2). These changes can have a variety of effects on health and development, including intellectual disability, slow growth, characteristic facial features, weak muscle tone (hypotonia), and abnormalities of the fingers and toes.

Ideogram of chromosome II

Ideogram of chromosome II

Chocolate Memories

noreply@blogger.com (Dallas Banks) — Mon, 16 Jan 2012 21:49:00 +0000

I appreciate the guest post, Emerson Moses

While watching direct TV trabuco cyn I came across a show on the Food Network where they were creating decadent sweets. It triggered a memory buried somewhere deep in my brain of a fudge recipe my mother used to make when I was a child. I picked up the phone and gave her a call to see if she too remembered the sweet confection she would stir up for me as a kid. Not only did she remember, but after a few minutes of scratching around, was able to locate the recipe. I grabbed a pen and pad and wrote it down. I was astonished how easy it was and to my surprise I had each and every ingredient needed to make it. Within minutes I had a bubbly pot of goodness waiting to be poured into a pan and chilled. When I gave some to my children after dinner, I knew the by the looks on their faces, this was going to be one of their favorites too.

Chromosome I

noreply@blogger.com (Dallas Banks) — Thu, 29 Dec 2011 01:09:00 +0000

I have decided that I am going to debut a new "series" in which I go over each of the human chromosomes and information pertaining to it. Of course, I'm going to start off with Chromosome #1.

What is Chromosome I?
Chromosome 1 is the largest human chromosome, spanning about 247 million DNA building blocks (base pairs) and representing approximately 8 percent of the total DNA in cells. Chromosome 1 likely contains more than 3,000 genes, which perform a variety of different roles in the body.

How Do Changes in Chromosome I Affect Health?
The following chromosomal conditions are associated with changes in chromosome I (Not a complete list):

1p36 deletion syndrome

1p36 deletion syndrome is caused by a deletion of genetic material from a specific region in the short (p) arm of chromosome 1. The signs and symptoms of this disorder, which include intellectual disability, distinctive facial features, and structural abnormalities in several body systems, are probably related to the loss of multiple genes in this region. The size of the deletion varies among affected individuals

Neuroblastoma

Neuroblastoma is a type of cancerous tumor composed of immature nerve cells (neuroblasts). These deletions are somatic mutations, which means they occur during a person's lifetime and are present only in the cells that become cancerous. About 25 percent of people with neuroblastoma have a deletion of 1p36.1-1p36.3, which is associated with a more severe form of neuroblastoma. Researchers believe the deleted region could contain a gene that keeps cells from growing and dividing too quickly or in an uncontrolled way, called a tumor suppressor gene. When tumor suppressor genes are deleted, cancer can occur. Researchers have identified several possible tumor suppressor genes in the deleted region of chromosome 1, and more research is needed to understand what role these genes play in neuroblastoma development.

Thrombocytopenia-absent radius syndrome

Everyone diagnosed with thrombocytopenia-absent radius (TAR) syndrome, which is characterized by bleeding problems and abnormal development of the forearms, has had a deletion of genetic material on chromosome 1. The deletion removes about 200,000 DNA building blocks (200 kilobases, or 200 kb) from the long (q) arm of the chromosome at position 1q21.1. This section of the chromosome contains 11 genes. The loss of multiple genes in this region is believed to be responsible for TAR syndrome. Not all people who inherit the deletion of genetic material on chromosome 1 associated with TAR syndrome will develop the disorder. Even within a single family, some people with the deletion may have TAR syndrome while others are unaffected. For this reason, researchers believe that the 1q21.1 200 kb deletion is needed to cause TAR syndrome but that some other, unknown genetic change must also be present.

Diagramming Chromosome I
Below is an ideogram of Chromosome I, which shows its relative size and banding pattern. The banding pattern is the pattern of dark and light areas on the chromosome that are used to identify the location of genes on each chromosome.

Team Discovers Cause Of Rare Disease Childhood Disorder Called PKD Linked To Genetic Mutations

noreply@blogger.com (Dallas Banks) — Mon, 19 Dec 2011 21:18:00 +0000

A large, international team of researchers led by scientists at the University of California, San Francisco has identified the gene that causes a rare childhood neurological disorder called PKD/IC, or "paroxysmal kinesigenic dyskinesia with infantile convulsions," a cause of epilepsy in babies and movement disorders in older children.

The study involved clinics in cities as far flung as Tokyo, New York, London and Istanbul and may improve the ability of doctors to diagnose PKD/IC, and it may shed light on other movement disorders, likeParkinson's disease.

The culprit behind the disease turns out to be a mysterious gene found in the brain called PRRT2. Nobody knows what this gene does, and it bears little resemblance to anything else in the human genome.

"This is both exciting and a little bit scary," said Louis Ptacek, MD, who led the research. Ptacek is the John C. Coleman Distinguished Professor of Neurology at UCSF and a Howard Hughes Medical Institute Investigator.

Discovering the gene that causes PKD/IC will help researchers understand how the disease works. It gives doctors a potential new way of definitively diagnosing the disease by looking for genetic mutations in the gene. The work may also shed light on other conditions that are characterized by movement disorders, including possibly Parkinson's disease.

"Understanding the underlying biology of this disease is absolutely going to help us understand movement disorders in general," Ptacek said.

About the Disease

PKD/IC strikes infants with epileptic seizures that generally disappear within a year or two. However, the disease often reemerges later in childhood as a movement disorder in which children suffer sudden, startling, involuntary jerks when they start to move. Even thinking about moving is enough to cause some of these children to jerk involuntarily.

The disease is rare, and Ptacek estimates strikes about one out of every 100,000 people in the United States. At the same time, the disease is classified as "idiopathic" which is just another way of saying we don't really understand it, Ptacek said.

If you take an image of the brain by MRI, patients with the disease all look completely normal. There are no injuries, tumors or other obvious signs that account for the movements as is often the case with movement disorders. Work with patients in the clinic had suggested a genetic cause, however.

"Sometimes we trace the family tree, and lo and behold, there is a history of it," said Ptacek. In the last several years, he and his colleagues have developed a large cohort of patients whose families have a history of the disease.

The new research was based on a cohort of 103 such families that included one or more members with the disease. Genetic testing of these families led to the researchers to mutations in the PRRT2 gene, which cause the proteins the gene encodes to shorten or disappear entirely in the brain and spinal cord, where they normally reside.

One possible explanation for the resulting neurological symptoms, the researchers found, relates to a loss of neuronal regulation. When the genetic mutations cause the gene products to go missing, the nerve cells where they normally appear may become overly excited, firing too frequently or strongly and leading to the involuntary movements.
Credit/References:
University of California, San Francisco. (2011, December 19). "Team Discovers Cause Of Rare Disease Childhood Disorder Called PKD Linked To Genetic Mutations." Medical News Today. Retrieved from
http://www.medicalnewstoday.com/releases/239425.php.

Mom and Me

noreply@blogger.com (Dallas Banks) — Mon, 19 Dec 2011 21:14:00 +0000

Contributed by Alva Bender

Mom and I had been fighting a lot over the last few months so I suggested we go to counseling. I know that sounds crazy but since I live with my parentsI figured it was smarter to try and fix our relationship for the long haul rather than spend years and years going over the same exact issues time and again. It was actually a really good decision because she and I are better than we’ve ever been and we’re communicating on a whole new level. She sent me to www.GiveADish.com the other day and had me pick out a satellite package without micromanaging me and I asked her to meet my boyfriend for the first time in my life. I feel like we’re both more excited about being around each other than we’ve been in years but you know, we’ve got a long way to go to become best friends. But maybe that’s just not the type of relationship we were meant to have at the end of the day!

Garrod's Fourth Inborn Error Of Metabolism: Modern Genetics Answers Age-Old Question

noreply@blogger.com (Dallas Banks) — Wed, 02 Nov 2011 19:40:00 +0000

Garrod's Fourth Inborn Error Of Metabolism: Modern Genetics Answers Age-Old Question
Quite an interesting article, I would definitely suggest you read this if you have any interest in inborn errors of metabolism, this article primarily focuses on pentosuria, which is an inherited condition that is often mistaken for diabetes.

A homemade kids vampire costume for the record books

noreply@blogger.com (Dallas Banks) — Sat, 22 Oct 2011 19:12:00 +0000

Guest post written by Sarah Jones

I've always loved sewing and don't hesitate to break out my sewing machine whenever my kids need a costume or something mended. I think that they know that and especially appreciate it when Halloween rolls around every year. This year my son told me that he wanted to dress up as a vampire, but as a kid vampire. He told me that he wanted his outfit to be really cool, so I started thinking about it a few weeks ago and have started working on it.

He really loves space and rocket ships, so I thought that it would be cool to make him a cape with a lining of fabric with space ships all over it. I used my Clear Wireless Internet 4G to find a good pattern for a cape and set to work on it.

When I told him my idea for it, he was so impressed! So far the homemade kids vampire costume is looking so cute, but cool to an 8-year-old boy. I just have to get him some fangs and he'll be set!

Another Blog I'm Working On...

noreply@blogger.com (Dallas Banks) — Sat, 15 Oct 2011 15:58:00 +0000

So, a group of my friends in college invited me to help them with their blog. I will still be posting to this blog, but I thought I should let you all know about this blog and if your curiosity gets the best of you, you should definitely check it out. The site is called http://redshirtcrew.blogspot.com/. It's just starting, but it's going to be great. It's a unique concept with different postings by all of the different authors at different days of the week about whatever strikes our fancy. Also, we will upload a new podcast every week, guaranteed to be full of random and hilarious content that will keep you coming back for me. So, do me a favor, and check out http://redshirtcrew.blogspot.com! Do it!

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV)

noreply@blogger.com (Dallas Banks) — Fri, 14 Oct 2011 01:38:00 +0000

What is ACD/MPV?

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a disorder affecting the development of the lungs and their blood vessels. The disorder affects the millions of small air sacs (alveoli) in the lungs and the tiny blood vessels (capillaries) in the alveoli. It is through these alveolar capillaries that inhaled oxygen enters the bloodstream for distribution throughout the body and carbon dioxide leaves the bloodstream to be exhaled.

In ACD/MPV, the alveolar capillaries fail to develop normally. The number of capillaries is drastically reduced, and existing capillaries are improperly positioned within the walls of the alveoli. These abnormalities in capillary number and location impede the exchange of oxygen and carbon dioxide.

Other abnormalities of the blood vessels in the lungs also occur in ACD/MPV. The veins that carry blood from the lungs into the heart (pulmonary veins) are improperly positioned and may be abnormally bundled together with arteries that carry blood from the heart to the lungs (pulmonary arteries). The muscle tissue in the walls of the pulmonary arteries may be overgrown, resulting in thicker artery walls and a narrower channel. These changes restrict normal blood flow, which causes high blood pressure in the pulmonary arteries (pulmonary hypertension) and requires the heart to pump harder.

Most infants with ACD/MPV are born with additional abnormalities. These may include abnormal twisting (malrotation) of the large intestine or other malformations of the gastrointestinal tract. Cardiovascular and genitourinary abnormalities are also common in affected individuals.

Infants with ACD/MPV typically develop respiratory distress within a few minutes to a few hours after birth. They experience shortness of breath and cyanosis, which is a bluish appearance of the skin, mucous membranes, or the area underneath the fingernails caused by a lack of oxygen in the blood. Without lung transplantation, infants with ACD/MPV have not been known to survive past one year of age, and most affected infants live only a few weeks.

How common is ACD/MPV?

ACD/MPV is a rare disorder; its incidence is unknown. Approximately 200 infants with this disorder have been identified worldwide.

What are the genetic changes related to ACD/MPV?

ACD/MPV can be caused by mutations in the FOXF1 gene. The protein produced from the FOXF1 gene is a transcription factor, which means that it attaches (binds) to specific regions of DNA and helps control the activity of many other genes. The FOXF1 protein is important in development of the lungs and their blood vessels. The FOXF1 protein is also involved in the development of the gastrointestinal tract. Mutations in the FOXF1 gene that cause ACD/MPV result in an inactive protein that cannot regulate development, leading to abnormal formation of the pulmonary blood vessels and gastrointestinal tract.

ACD/MPV can also be caused by a deletion of genetic material on the long arm of chromosome 16 in a region known as 16q24.1. This region includes several genes, including the FOXF1 gene. Deletion of one copy of the FOXF1 gene in each cell reduces the production of the FOXF1 protein. A shortage of FOXF1 protein affects the development of pulmonary blood vessels and causes the main features of ACD/MPV. Researchers suggest that the loss of other genes in this region probably causes the additional abnormalities, such as heart defects, seen in some infants with this disorder. Like FOXF1, these genes also provide instructions for making transcription factors that regulate development of various body systems before birth.

In about 60 percent of affected infants, the genetic cause of ACD/MPV is unknown.

Can ACD/MPV be inherited?

ACD/MPV is usually not inherited, and most affected people have no history of the disorder in their family. The genetic changes associated with this condition usually occur during the formation of reproductive cells (eggs and sperm) or in early fetal development. When the condition is caused by a FOXF1 gene mutation or deletion, one altered or missing gene in each cell is sufficient to cause the disorder. Individuals with ACD/MPV do not pass the genetic change on to their children because they do not live long enough to reproduce.

A few families have been identified in which more than one sibling has ACD/MPV. It is not clear how ACD/MPV is inherited in these families because no genetic changes have been identified.

Arrhythmogenic right ventricular cardiomyopathy

noreply@blogger.com (Dallas Banks) — Wed, 12 Oct 2011 23:18:00 +0000

What is ARVC?

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a form of heart disease that usually appears in adulthood. ARVC is a disorder of the myocardium, which is the muscular wall of the heart. This condition causes part of the myocardium to break down over time, increasing the risk of an abnormal heartbeat (arrhythmia) and sudden death.

ARVC may not cause any symptoms in its early stages. However, affected individuals may still be at risk of sudden death, especially during strenuous exercise. When symptoms occur, they most commonly include a sensation of fluttering or pounding in the chest (palpitations), light-headedness, and fainting (syncope). Over time, ARVC can also cause shortness of breath and abnormal swelling in the legs or abdomen. If the myocardium becomes severely damaged in the later stages of the disease, it can lead to heart failure.

How common is ARVC?

ARVC occurs in an estimated 1 in 1,000 to 1 in 1,250 people. This disorder may be under-diagnosed because it can be difficult to detect in people with mild or no symptoms.

What genes are related to ARVC?

ARVC can result from mutations in at least eight genes. Many of these genes are involved in the function of desmosomes, which are structures that attach heart muscle cells to one another. Desmosomes provide strength to the myocardium and play a role in signaling between neighboring cells.

Mutations in the genes responsible for ARVC often impair the normal function of desmosomes. Without normal desmosomes, cells of the myocardium detach from one another and die, particularly when the heart muscle is placed under stress (such as during vigorous exercise). These changes primarily affect the myocardium surrounding the right ventricle, one of the two lower chambers of the heart. The damaged myocardium is gradually replaced by fat and scar tissue. As this abnormal tissue builds up, the walls of the right ventricle become stretched out, preventing the heart from pumping blood effectively. These changes also disrupt the electrical signals that control the heartbeat, which can lead to arrhythmia.

Gene mutations have been found in 30 to 40 percent of people with ARVC. Mutations in a gene called PKP2 are most common. In people without an identified mutation, the cause of the disorder is unknown. Researchers are looking for additional genetic factors, particularly those involved in the function of desmosomes, that may play a role in causing ARVC.

How do people inherit ARVC?

Up to half of all cases of ARVC appear to run in families. Most familial cases of the disease have an autosomal dominant pattern of inheritance, which means one copy of an altered gene in each cell is sufficient to cause the disorder.

Rarely, ARVC has an autosomal recessive pattern of inheritance, which means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Hereditary leiomyomatosis and renal cell cancer

noreply@blogger.com (Dallas Banks) — Sun, 09 Oct 2011 15:41:00 +0000

What is HLRCC?

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a disorder in which affected individuals tend to develop benign tumors containing smooth muscle tissue (leiomyomas) in the skin and, in females, the uterus. This condition also increases the risk of kidney cancer.

In this disorder, growths on the skin (cutaneous leiomyomas) typically develop in the third decade of life. Most of these growths arise from the tiny muscles around the hair follicles that cause "goosebumps". They appear as bumps or nodules on the trunk, arms, legs, and occasionally on the face. Cutaneous leiomyomas may be the same color as the surrounding skin, or they may be darker. Some affected individuals have no cutaneous leiomyomas or only a few, but the growths tend to increase in size and number over time. Cutaneous leiomyomas are often more sensitive than the surrounding skin to cold or light touch, and may be painful.

Most women with HLRCC also develop uterine leiomyomas (fibroids). While uterine fibroids are very common in the general population, women with HLRCC tend to have numerous large fibroids that appear earlier than in the general population.

Approximately 10 percent to 16 percent of people with HLRCC develop a type of kidney cancer called renal cell cancer. The signs and symptoms of renal cell cancer may include lower back pain, blood in the urine, or a mass in the kidney that can be felt upon physical examination. Some people with renal cell cancer have no symptoms until the disease is advanced. The average age at which people with HLRCC are diagnosed with kidney cancer is in their forties.

This disorder, especially if it appears in individuals or families without renal cell cancer, is also sometimes called multiple cutaneous leiomyomatosis (MCL) or multiple cutaneous and uterine leiomyomatosis (MCUL).

How common is HLRCC?

HLRCC has been reported in approximately 100 families worldwide. Its prevalence is unknown.

What genes are related to HLRCC?

Mutations in the FH gene cause hereditary leiomyomatosis and renal cell cancer. The FH gene provides instructions for making an enzyme called fumarase (also known as fumarate hydratase). This enzyme participates in an important series of reactions known as the citric acid cycle or Krebs cycle, which allows cells to use oxygen and generate energy. Specifically, fumarase helps convert a molecule called fumarate to a molecule called malate.

People with HLRCC are born with one mutated copy of the FH gene in each cell. The second copy of the FH gene in certain cells may also acquire mutations as a result of environmental factors such as ultraviolet radiation from the sun or a mistake that occurs as DNA copies itself during cell division.

FH gene mutations may interfere with the enzyme's role in the citric acid cycle, resulting in a buildup of fumarate. Researchers believe that the excess fumarate may interfere with the regulation of oxygen levels in the cell. Chronic oxygen deficiency (hypoxia) in cells with two mutated copies of the FH gene may encourage tumor formation and result in the tendency to develop leiomyomas and renal cell cancer.

How do people inherit HLRCC?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

Progressive Familial Intrahepatic Cholestasis

noreply@blogger.com (Dallas Banks) — Wed, 05 Oct 2011 14:55:00 +0000

Progressive familial intrahepatic cholestasis (PFIC) is a disorder that causes progressive liver disease, which typically leads to liver failure. In people with PFIC, liver cells are less able to secrete a digestive fluid called bile. The buildup of bile in liver cells causes liver disease in affected individuals.

Signs and symptoms of PFIC typically begin in infancy and are related to bile buildup and liver disease. Specifically, affected individuals experience severe itching, yellowing of the skin and whites of the eyes (jaundice), failure to gain weight and grow at the expected rate (failure to thrive), high blood pressure in the vein that supplies blood to the liver (portal hypertension), and an enlarged liver and spleen (hepatosplenomegaly).

There are three known types of PFIC: PFIC1, PFIC2, and PFIC3. The types are also sometimes described as shortages of particular proteins needed for normal liver function. Each type has a different genetic cause.

In addition to signs and symptoms related to liver disease, people with PFIC1 may have short stature, deafness, diarrhea, inflammation of the pancreas (pancreatitis), and low levels of fat-soluble vitamins (vitamins A, D, E, and K) in the blood. Affected individuals typically develop liver failure before adulthood.

The signs and symptoms of PFIC2 are typically related to liver disease only; however, these signs and symptoms tend to be more severe than those experienced by people with PFIC1. People with PFIC2 often develop liver failure within the first few years of life. Additionally, affected individuals are at increased risk of developing a type of liver cancer called hepatocellular carcinoma.

Most people with PFIC3 have signs and symptoms related to liver disease only. Signs and symptoms of PFIC3 usually do not appear until later in infancy or early childhood; rarely, people are diagnosed in early adulthood. Liver failure can occur in childhood or adulthood in people with PFIC3.

How common is progressive familial intrahepatic cholestasis?

PFIC is estimated to affect 1 in 50,000 to 100,000 people worldwide. PFIC type 1 is much more common in the Inuit population of Greenland and the Old Order Amish population of the United States.

What genes are related to progressive familial intrahepatic cholestasis?

Mutations in the ATP8B1, ABCB11, and ABCB4 genes can cause PFIC.

ATP8B1 gene mutations cause PFIC1. The ATP8B1 gene provides instructions for making a protein that helps to maintain an appropriate balance of bile acids, a component of bile. This process, known as bile acid homeostasis, is critical for the normal secretion of bile and the proper functioning of liver cells. In its role in maintaining bile acid homeostasis, some researchers believe that the ATP8B1 protein is involved in moving certain fats across cell membranes. Mutations in the ATP8B1 gene result in the buildup of bile acids in liver cells, damaging these cells and causing liver disease. The ATP8B1 protein is found throughout the body, but it is unclear how a lack of this protein causes short stature, deafness, and other signs and symptoms of PFIC1.

Mutations in the ABCB11 gene are responsible for PFIC2. The ABCB11 gene provides instructions for making a protein called the bile salt export pump (BSEP). This protein is found in the liver, and its main role is to move bile salts (a component of bile) out of liver cells. Mutations in the ABCB11 gene result in the buildup of bile salts in liver cells, damaging these cells and causing liver disease.

ABCB4 gene mutations cause PFIC3. The ABCB4 gene provides instructions for making a protein that moves certain fats called phospholipids across cell membranes. Outside liver cells, phospholipids attach (bind) to bile acids. Large amounts of bile acids can be toxic when they are not bound to phospholipids. Mutations in the ABCB4 gene lead to a lack of phospholipids available to bind to bile acids. A buildup of free bile acids damages liver cells and leads to liver disease.

Some people with PFIC do not have a mutation in the ATP8B1, ABCB11, or ABCB4 gene. In these cases, the cause of the condition is unknown.

How do people inherit progressive familial intrahepatic cholestasis?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

X-linked lymphoproliferative disease

noreply@blogger.com (Dallas Banks) — Mon, 03 Oct 2011 14:34:00 +0000

What is XLP?

X-linked lymphoproliferative disease (XLP) is a disorder of the immune system and blood-forming cells that is found almost exclusively in males. More than half of individuals with this disorder experience an exaggerated immune response to the Epstein-Barr virus (EBV). EBV is a very common virus that eventually infects most humans. In some people it causes infectious mononucleosis (commonly known as "mono"). Normally, after initial infection, EBV remains in certain immune system cells (lymphocytes) called B cells. However, the virus is generally inactive (latent) because it is controlled by other lymphocytes called T cells that specifically target EBV-infected B cells.

People with XLP may respond to EBV infection by producing abnormally large numbers of T cells, B cells, and other lymphocytes called macrophages. This proliferation of immune cells often causes a life-threatening reaction called hemophagocytic lymphohistiocytosis. Hemophagocytic lymphohistiocytosis causes fever, destroys blood-producing cells in the bone marrow, and damages the liver. The spleen, heart, kidneys, and other organs and tissues may also be affected. In some individuals with XLP, hemophagocytic lymphohistiocytosis or related symptoms may occur without EBV infection.

About one-third of people with XLP experience dysgammaglobulinemia, which means they have abnormal levels of some types of antibodies. Antibodies are proteins that attach to specific foreign particles and germs, marking them for destruction. Individuals with dysgammaglobulinemia are prone to recurrent infections.
Cancers of immune system cells (lymphomas) occur in about one-third of affected individuals.

Without allogeneic stem cell transplantation, in which a patient's diseased blood-forming cells (a type of stem cell) are replaced with stem cells from a healthy donor, most people with XLP survive only into childhood. Death usually results from hemophagocytic lymphohistiocytosis associated with EBV infection.

How common is XLP?

XLP is estimated to occur in about 1 per million males worldwide.

What genes are related to XLP?

Mutations in the SH2D1A and XIAP genes cause XLP. XLP caused by SH2D1A gene mutations is sometimes called classic XLP or XLP1. When the disorder is caused by XIAP gene mutations it may be known as XLP2. Because the frequency of the various features of XLP differ between the two types, and certain immune cell abnormalities identified in XLP1 have not been observed in XLP2, some researchers believe that these should actually be considered similar but separate disorders.

The SH2D1A gene provides instructions for making a protein called signaling lymphocyte activation molecule (SLAM) associated protein (SAP). This protein is involved in the functioning of lymphocytes that destroy other cells (cytotoxic lymphocytes) and is necessary for the development of specialized T cells called natural killer T cells. The SAP protein also helps control immune reactions by triggering self-destruction (apoptosis) of cytotoxic lymphocytes when they are no longer needed.

Some SH2D1A gene mutations impair SAP function. Others result in an abnormally short protein that is unstable or nonfunctional, or prevent any SAP from being produced. The loss of functional SAP disrupts proper signaling in the immune system and may prevent the body from controlling the immune reaction to EBV infection. In addition, lymphomas may develop when defective lymphocytes are not properly destroyed by apoptosis.

The XIAP gene provides instructions for making a protein that helps protect cells from undergoing apoptosis in response to certain signals. XIAP gene mutations can lead to an absence of XIAP protein or decrease the amount of XIAP protein that is produced. It is unknown how a lack of XIAP protein results in the signs and symptoms of XLP, or why features of this disorder differ somewhat between people with XIAP and SH2D1A gene mutations. For example, affected individuals with XIAP gene mutations have not been known to develop lymphoma; they may also develop hemophagocytic lymphohistiocytosis with or without EBV exposure or with another virus called cytomegalovirus.

How do people inherit XLP?

This condition is generally inherited in an X-linked recessive pattern. The genes associated with this condition are located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of an associated gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of an associated gene, males are affected by X-linked recessive disorders much more frequently than females. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Rarely, a female carrying one altered copy of the SH2D1A or XIAP gene in each cell may develop signs and symptoms of this condition.

Ornithine Transcarbamylase Deficiency

noreply@blogger.com (Dallas Banks) — Fri, 30 Sep 2011 14:58:00 +0000

What is ornithine transcarbamylase deficiency?

Ornithine transcarbamylase deficiency is an inherited disorder that causes ammonia to accumulate in the blood. Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high. The nervous system is especially sensitive to the effects of excess ammonia.

Ornithine transcarbamylase deficiency often becomes evident in the first few days of life. An infant with ornithine transcarbamylase deficiency may be lacking in energy (lethargic) or unwilling to eat, and have poorly-controlled breathing rate or body temperature. Some babies with this disorder may experience seizures or unusual body movements, or go into a coma. Complications from ornithine transcarbamylase deficiency may include developmental delay and intellectual disability. Progressive liver damage, skin lesions, and brittle hair may also be seen.

In some affected individuals, signs and symptoms of ornithine transcarbamylase may be less severe, and may not appear until later in life.

How common is ornithine transcarbamylase deficiency?

Ornithine transcarbamylase deficiency is believed to occur in approximately 1 in every 80,000 people.

What genes are related to ornithine transcarbamylase deficiency?

Mutations in the OTC gene cause ornithine transcarbamylase deficiency.

Ornithine transcarbamylase deficiency belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of reactions that occurs in liver cells. It processes excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the kidneys.

In ornithine transcarbamylase deficiency, the enzyme that starts a specific reaction within the urea cycle is damaged or missing. The urea cycle cannot proceed normally, and nitrogen accumulates in the bloodstream in the form of ammonia.

Ammonia is especially damaging to the nervous system, so ornithine transcarbamylase deficiency causes neurological problems as well as eventual damage to the liver.

How do people inherit ornithine transcarbamylase deficiency?

Ornithine transcarbamylase deficiency is an X-linked disorder. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), mutations in both copies of the gene will cause the disorder. Some females with only one altered copy of the OTC gene also show signs and symptoms of ornithine transcarbamylase deficiency.

Familial adenomatous polyposis

noreply@blogger.com (Dallas Banks) — Thu, 29 Sep 2011 03:31:00 +0000

What is familial adenomatous polyposis?

Familial adenomatous polyposis (FAP) is an inherited disorder characterized by cancer of the large intestine (colon) and rectum. People with the classic type of familial adenomatous polyposis may begin to develop multiple noncancerous (benign) growths (polyps) in the colon as early as their teenage years. Unless the colon is removed, these polyps will become malignant (cancerous). The average age at which an individual develops colon cancer in classic familial adenomatous polyposis is 39 years. Some people have a variant of the disorder, called attenuated familial adenomatous polyposis, in which polyp growth is delayed. The average age of colorectal cancer onset for attenuated familial adenomatous polyposis is 55 years.

In people with classic familial adenomatous polyposis, the number of polyps increases with age, and hundreds to thousands of polyps can develop in the colon. Also of particular significance are noncancerous growths called desmoid tumors. These fibrous tumors usually occur in the tissue covering the intestines and may be provoked by surgery to remove the colon. Desmoid tumors tend to recur after they are surgically removed. In both classic familial adenomatous polyposis and its attenuated variant, benign and malignant tumors are sometimes found in other places in the body, including the duodenum (a section of the small intestine), stomach, bones, skin, and other tissues. People who have colon polyps as well as growths outside the colon are sometimes described as having Gardner syndrome.

A milder type of familial adenomatous polyposis, called autosomal recessive familial adenomatous polyposis, has also been identified. People with the autosomal recessive type of this disorder have fewer polyps than those with the classic type. Fewer than 100 polyps typically develop, rather than hundreds or thousands. The autosomal recessive type of this disorder is caused by mutations in a different gene than the classic and attenuated types of familial adenomatous polyposis.

How common is familial adenomatous polyposis?

The reported incidence of familial adenomatous polyposis varies from 1 in 7,000 to 1 in 22,000 individuals.

What genes are related to familial adenomatous polyposis?

Mutations in the APC gene cause both classic and attenuated familial adenomatous polyposis. These mutations affect the ability of the cell to maintain normal growth and function. Cell overgrowth resulting from mutations in the APC gene leads to the colon polyps seen in familial adenomatous polyposis. Although most people with mutations in the APC gene will develop colorectal cancer, the number of polyps and the time frame in which they become malignant depend on the location of the mutation in the gene.

Mutations in the MUTYH gene cause autosomal recessive familial adenomatous polyposis (also called MYH-associated polyposis). Mutations in this gene prevent cells from correcting mistakes that are made when DNA is copied (DNA replication) in preparation for cell division. As these mistakes build up in a person's DNA, the likelihood of cell overgrowth increases, leading to colon polyps and the possibility of colon cancer.

How do people inherit familial adenomatous polyposis?

Familial adenomatous polyposis can have different inheritance patterns.

When familial adenomatous polyposis results from mutations in the APC gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.

When familial adenomatous polyposis results from mutations in the MUTYH gene, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.

Autoimmune Polyglandular Syndrome, type 1

noreply@blogger.com (Dallas Banks) — Tue, 27 Sep 2011 16:07:00 +0000

What is autoimmune polyglandular syndrome, type 1?

Autoimmune polyglandular syndrome, type 1 is an inherited condition that affects many of the body's organs. It is one of many autoimmune diseases, which are disorders that occur when the immune system malfunctions and attacks the body's tissues and organs by mistake.

In most cases, the signs and symptoms of autoimmune polyglandular syndrome, type 1 begin in childhood or adolescence. This condition is characterized by three specific features: mucocutaneous candidiasis, hypoparathyroidism, and Addison disease. Affected individuals typically have at least two of these features, and many have all three.

Mucocutaneous candidiasis is a fungal infection that affects the skin and mucous membranes, such as the moist lining of the nose and mouth. In children with autoimmune polyglandular syndrome, type 1, these infections last a long time and tend to recur. Many affected children also develop hypoparathyroidism, which is a malfunction of the parathyroid glands. These glands secrete a hormone that regulates the body's use of calcium and phosphorus. Hypoparathyroidism can cause a tingling sensation in the lips, fingers, and toes; muscle pain and cramping; weakness; and fatigue. The third major feature, Addison disease, results from a malfunction of the small hormone-producing glands on top of each kidney (adrenal glands). The main features of Addison disease include fatigue, muscle weakness, loss of appetite, weight loss, low blood pressure, and changes in skin coloring.

Autoimmune polyglandular syndrome, type 1 can cause a variety of additional signs and symptoms, although they occur less often. Complications of this disorder can affect the skin and nails, the gonads (ovaries and testicles), the eyes, a butterfly-shaped gland at the base of the neck called the thyroid, and the digestive system. Type 1 diabetes also occurs in some patients with this condition.

How common is autoimmune polyglandular syndrome, type 1?

Autoimmune polyglandular syndrome, type 1 is thought to be a rare condition, with about 500 cases reported worldwide. This condition occurs more frequently in certain populations, including Iranian Jews, Sardinians, and Finns.

What genes are related to autoimmune polyglandular syndrome, type 1?

Mutations in the AIRE gene cause autoimmune polyglandular syndrome, type 1.

The AIRE gene provides instructions for making a protein called the autoimmune regulator. As its name suggests, this protein plays a critical role in regulating certain aspects of immune system function. Specifically, it helps the body distinguish its own proteins and cells from those of foreign invaders (such as bacteria and viruses). This distinction is critical because to remain healthy, a person's immune system must be able to identify and destroy potentially harmful invaders while sparing the body's normal tissues.

Mutations in the AIRE gene reduce or eliminate the function of the autoimmune regulator protein. Without enough of this protein, the immune system can turn against itself and attack the body's own organs. This reaction, which is known as autoimmunity, results in inflammation and can damage otherwise healthy cells and tissues. Damage to the adrenal glands, parathyroid glands, and other organs underlies many of the major features of autoimmune polyglandular syndrome, type 1. It remains unclear why people with this condition tend to get candidiasis infections.

Although most of the characteristic features of autoimmune polyglandular syndrome, type 1 result from mutations in the AIRE gene, researchers believe that variations in other genes may help explain why the signs and symptoms of this condition can vary among affected individuals.

How do people inherit autoimmune polyglandular syndrome, type 1?

N-acetylglutamate synthase deficiency

noreply@blogger.com (Dallas Banks) — Tue, 20 Sep 2011 16:33:00 +0000

What is N-acetylglutamate synthase deficiency?

N-acetylglutamate synthase deficiency is an inherited disorder that causes ammonia to accumulate in the blood. Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high. The nervous system is especially sensitive to the effects of excess ammonia.

N-acetylglutamate synthase deficiency may become evident in the first few days of life. An infant with this condition may be lacking in energy (lethargic) or unwilling to eat, and have a poorly controlled breathing rate or body temperature. Some babies with this disorder may experience seizures or unusual body movements, or go into a coma. Complications of N-acetylglutamate synthase deficiency may include developmental delay and intellectual disability.

In some affected individuals, signs and symptoms of N-acetylglutamate synthase deficiency are less severe, and do not appear until later in life. Some people with this form of the disorder cannot tolerate high-protein foods such as meat. They may experience sudden episodes of ammonia toxicity, resulting in vomiting, lack of coordination, confusion or coma, in response to illness or other stress.

How common is N-acetylglutamate synthase deficiency?

N-acetylglutamate synthase deficiency is a very rare disorder. Only a few cases have been reported worldwide, and the overall incidence is unknown.

What genes are related to N-acetylglutamate synthase deficiency?

Mutations in the NAGS gene cause N-acetylglutamate synthase deficiency.

N-acetylglutamate synthase deficiency belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of reactions that occurs in liver cells. This cycle processes excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the kidneys.
The NAGS gene provides instructions for making the enzyme N-acetylglutamate synthase, which helps produce a compound called N-acetylglutamate. This compound is needed to activate another enzyme, carbamoyl phosphate synthetase I, which controls the first step of the urea cycle.

In people with N-acetylglutamate synthase deficiency, N-acetylglutamate is not available in sufficient quantities, or is not present at all. As a result, urea cannot be produced normally, and excess nitrogen accumulates in the blood in the form of ammonia. This accumulation of ammonia causes the neurological problems and other signs and symptoms of N-acetylglutamate synthase deficiency.

How do people inherit N-acetylglutamate synthase deficiency?

Alpha-1 Antitrypsin Deficiency

noreply@blogger.com (Dallas Banks) — Wed, 14 Sep 2011 19:15:00 +0000

What is alpha-1 antitrypsin deficiency?

Alpha-1 antitrypsin deficiency is an inherited disorder that may cause lung disease and liver disease. People with alpha-1 antitrypsin deficiency usually develop the first signs and symptoms of lung disease between ages 20 and 50. The earliest symptoms are shortness of breath following mild activity, reduced ability to exercise, and wheezing. Other signs and symptoms can include unintentional weight loss, recurring respiratory infections, fatigue, and rapid heartbeat upon standing. Affected individuals often develop emphysema, which is a lung disease caused by damage to the small air sacs in the lungs (alveoli). Characteristic features of emphysema include difficulty breathing, a hacking cough, and a barrel-shaped chest. Smoking or exposure to tobacco smoke accelerates the appearance of emphysema symptoms and damage to the lungs.

About 10 percent of infants with alpha-1 antitrypsin deficiency develop liver disease, which often causes yellowing of the skin and whites of the eyes (jaundice). Approximately 15 percent of affected adults develop liver damage (cirrhosis) due to the formation of scar tissue in the liver. Signs of cirrhosis include a swollen abdomen, swollen feet or legs, and jaundice. Individuals with alpha-1 antitrypsin deficiency are also at risk for developing a type of liver cancer called hepatocellular carcinoma.

In rare cases, people with alpha-1 antitrypsin deficiency develop a skin condition called panniculitis, which is characterized by hardened skin with painful lumps or patches. Panniculitis varies in severity and can occur at any age.

How common is alpha-1 antitrypsin deficiency?

Alpha-1 antitrypsin deficiency occurs worldwide, but its prevalence varies by population. This disorder affects about 1 in 1,500 to 3,500 individuals with European ancestry. It is uncommon in people of Asian descent. Many individuals with alpha-1 antitrypsin deficiency are likely undiagnosed, particularly those with the common diagnosis of chronic obstructive pulmonary disease (COPD).

What genes are related to alpha-1 antitrypsin deficiency?

Mutations in the SERPINA1 gene cause alpha-1 antitrypsin deficiency. This gene provides instructions for making a protein called alpha-1 antitrypsin, which protects the body from a powerful enzyme called neutrophil elastase. Neutrophil elastase is released from white blood cells to fight infection, but it can attack normal tissues (especially the lungs) if not tightly controlled by alpha-1 antitrypsin.

Mutations in the SERPINA1 gene can lead to a shortage (deficiency) of alpha-1 antitrypsin or an abnormal form of the protein that cannot control neutrophil elastase. Without enough functional alpha-1 antitrypsin, neutrophil elastase destroys alveoli and causes lung disease. Abnormal alpha-1 antitrypsin can also accumulate in the liver and damage this organ.

How do people inherit alpha-1 antitrypsin deficiency?

This condition is inherited in an autosomal codominant pattern. Codominance means that two different versions of the gene may be active (expressed), and both versions contribute to the genetic trait.
The most common version (allele) of the SERPINA1 gene, called M, produces normal levels of alpha-1 antitrypsin. Most people in the general population have two copies of the M allele (MM) in each cell. Other versions of the SERPINA1 gene lead to reduced levels of alpha-1 antitrypsin. For example, the S allele produces moderately low levels of this protein, and the Z allele produces very little alpha-1 antitrypsin. Individuals with two copies of the Z allele (ZZ) in each cell are likely to have alpha-1 antitrypsin deficiency. Those with the SZ combination have an increased risk of developing lung diseases (such as emphysema), particularly if they smoke.

Worldwide, it is estimated that 161 million people have one copy of the S or Z allele and one copy of the M allele in each cell (MS or MZ). Individuals with an MS (or SS) combination usually produce enough alpha-1 antitrypsin to protect the lungs. People with MZ alleles, however, have a slightly increased risk of impaired lung or liver function.

Li-Fraumeni syndrome

noreply@blogger.com (Dallas Banks) — Wed, 07 Sep 2011 11:43:00 +0000

What is Li-Fraumeni syndrome?

Li-Fraumeni syndrome is a rare disorder that greatly increases the risk of developing several types of cancer, particularly in children and young adults.

Soft tissue sarcoma of the leg

The cancers most often associated with Li-Fraumeni syndrome include breast cancer, a form of bone cancer called osteosarcoma, and cancers of soft tissues (such as muscle) called soft tissue sarcomas. Other cancers commonly seen in this syndrome include brain tumors, cancers of blood-forming tissues (leukemias), and a cancer called adrenocortical carcinoma that affects the outer layer of the adrenal glands (small hormone-producing glands on top of each kidney). Several other types of cancer also occur more frequently in people with Li-Fraumeni syndrome.

A very similar condition called Li-Fraumeni-like syndrome shares many of the features of classic Li-Fraumeni syndrome. Both conditions significantly increase the chances of developing multiple cancers beginning in childhood; however, the pattern of specific cancers seen in affected family members is different.

How common is Li-Fraumeni syndrome?

The exact prevalence of Li-Fraumeni is unknown. One U.S. registry of Li-Fraumeni syndrome patients suggests that about 400 people from 64 families have this disorder.

What genes are related to Li-Fraumeni syndrome?

The CHEK2 and TP53 genes are associated with Li-Fraumeni syndrome.

More than half of all families with Li-Fraumeni syndrome have inherited mutations in the TP53 gene. TP53 is a tumor suppressor gene, which means that it normally helps control the growth and division of cells. Mutations in this gene can allow cells to divide in an uncontrolled way and form tumors. Other genetic and environmental factors are also likely to affect the risk of cancer in people with TP53 mutations.

A few families with cancers characteristic of Li-Fraumeni syndrome and Li-Fraumeni-like syndrome do not have TP53 mutations, but have mutations in the CHEK2 gene. Like the TP53 gene, CHEK2 is a tumor suppressor gene. Researchers are uncertain whether CHEK2 mutations actually cause these conditions or are merely associated with an increased risk of certain cancers (including breast cancer).

How do people inherit Li-Fraumeni syndrome?

Li-Fraumeni syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase the risk of developing cancer. In most cases, an affected person has a parent and other family members with cancers characteristic of the condition.

Carbamoyl Phosphate Synthetase I Deficiency

noreply@blogger.com (Dallas Banks) — Thu, 01 Sep 2011 20:54:00 +0000

What is carbamoyl phosphate synthetase I deficiency?

Carbamoyl Phosphate Synthetase

Carbamoyl phosphate synthetase I deficiency is an inherited disorder that causes ammonia to accumulate in the blood. Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high. The nervous system is especially sensitive to the effects of excess ammonia.

Carbamoyl phosphate synthetase I deficiency often becomes evident in the first few days of life. An infant with this condition may be lacking in energy (lethargic) or unwilling to eat, and have a poorly controlled breathing rate or body temperature. Some babies with this disorder may experience seizures or unusual body movements, or go into a coma. Complications of carbamoyl phosphate synthetase I deficiency may include developmental delay and intellectual disability.

In some affected individuals, signs and symptoms of carbamoyl phosphate synthetase I deficiency may be less severe, and may not appear until later in life.

How common is carbamoyl phosphate synthetase I deficiency?

Carbamoyl phosphate synthetase I deficiency is a rare disorder; its overall incidence is unknown. Researchers in Japan have estimated that it occurs in 1 in 800,000 newborns in that country.

What genes are related to carbamoyl phosphate synthetase I deficiency?

Mutations in the CPS1 gene cause carbamoyl phosphate synthetase I deficiency.

Carbamoyl phosphate synthetase I deficiency belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of reactions that occurs in liver cells. This cycle processes excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the kidneys.

In carbamoyl phosphate synthetase I deficiency, the enzyme that regulates the urea cycle is damaged or missing. The urea cycle cannot proceed normally, and nitrogen accumulates in the bloodstream in the form of ammonia. Ammonia is especially damaging to the nervous system, and excess ammonia causes neurological problems and other signs and symptoms of carbamoyl phosphate synthetase I deficiency.

How do people inherit carbamoyl phosphate synthetase I deficiency?

X-linked adrenoleukodystrophy

noreply@blogger.com (Dallas Banks) — Mon, 29 Aug 2011 03:52:00 +0000

What is X-linked adrenoleukodystrophy?

X-linked adrenoleukodystrophy is a disorder that occurs most often in males. It mainly affects the nervous system and the adrenal glands, which are small glands located on top of each kidney. People with this disorder often have progressive destruction of the fatty covering (myelin) that insulates nerves in the brain and spinal cord. They may also have a shortage of certain hormones caused by damage to the outer layer of the adrenal glands (adrenal cortex). This hormonal deficiency is known as adrenocortical insufficiency.
There are three distinct types of X-linked adrenoleukodystrophy: a childhood cerebral form, an adrenomyeloneuropathy type, and a type called Addison disease only.

Children with the cerebral form of X-linked adrenoleukodystrophy experience learning and behavioral problems that usually appear by the age of 10. Over time the symptoms worsen, and these children may have difficulty reading, writing, understanding speech, and comprehending written material. Additional signs and symptoms of the cerebral form include aggressive behavior, vision problems, and impaired adrenal gland function. The rate at which this disorder progresses is variable; however, total disability within several years is not uncommon.

Signs and symptoms of the adrenomyeloneuropathy type appear between early adulthood and middle age. Affected individuals develop progressive stiffness and weakness in their legs (paraparesis), experience urinary and genital tract disorders, and often show some degree of brain dysfunction. Most people with the adrenomyeloneuropathy type also have adrenocortical insufficiency.

When adrenocortical insufficiency occurs without any other symptoms it is sometimes called Addison disease. People with X-linked adrenoleukodystrophy whose only symptom is adrenocortical insufficiency are said to have the Addison disease only form. Adrenocortical insufficiency may cause weakness, weight loss, skin changes, vomiting, and coma. Most people initially diagnosed with the Addison disease only form of X-linked adrenoleukodystrophy eventually develop all the signs of adrenomyeloneuropathy by the time they reach middle age.

For reasons that are unclear, different types of X-linked adrenoleukodystrophy can be seen in affected individuals within the same family.

How common is X-linked adrenoleukodystrophy?

The prevalence of X-linked adrenoleukodystrophy is approximately 1 in 20,000 individuals worldwide. This condition occurs with a similar frequency in all populations.

What genes are related to X-linked adrenoleukodystrophy?

Mutations in the ABCD1 gene cause X-linked adrenoleukodystrophy. The ABCD1 gene provides instructions for producing the adrenoleukodystrophy protein (ALDP), which is involved in transporting molecules into peroxisomes. Peroxisomes are small sacs within cells that process many types of molecules. Inside peroxisomes, ALDP is thought to play a role in the breakdown of certain fats (very long-chain fatty acids or VLCFAs).

ABCD1 gene mutations result in a shortage (deficiency) of ALDP. When this protein is lacking, the breakdown of very long-chain fatty acids is disrupted, causing abnormally high levels of these fats in the body. The accumulation of very long-chain fatty acids may be toxic to the adrenal cortex and the myelin membranes that surround many of the nerves in the brain and spinal cord.

How do people inherit X-linked adrenoleukodystrophy?

This condition is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. Because females have two copies of the X chromosome, one altered copy of the gene in each cell usually leads to less severe symptoms in females than in males, or may cause no symptoms at all.

Many females who carry one altered copy of the ABCD1 gene do not have any features of X-linked adrenoleukodystrophy; however some females with one altered copy of the gene have medical problems associated with this disorder. The signs and symptoms of X-linked adrenoleukodystrophy tend to appear at a later age in females than in males. In affected women, the disorder is usually similar to the adrenomyeloneuropathy type, although it may occasionally impair adrenal gland function. Less commonly, affected females have signs of the childhood cerebral form of this condition.

Infantile systemic hyalinosis

noreply@blogger.com (Dallas Banks) — Sat, 27 Aug 2011 01:17:00 +0000

What is infantile systemic hyalinosis?

Infantile systemic hyalinosis is a disorder that severely affects many areas of the body, including the skin, joints, bones, and internal organs. Hyalinosis refers to the abnormal accumulation of a clear (hyaline) substance in body tissues. The signs and symptoms of this condition are present at birth or develop within the first few months of life. Infantile systemic hyalinosis is characterized by painful skin bumps that frequently appear on the hands, neck, scalp, ears, and nose (pictured on the right). They also develop in joint creases and the genital region. These skin bumps may be large or small and often increase in number over time.

Lumps of noncancerous tissue also form in the muscles and internal organs of children with infantile systemic hyalinosis, causing pain and severe complications. Most affected individuals develop a condition called protein-losing enteropathy due to the formation of lumps in their intestines. This condition results in severe diarrhea, failure to gain weight and grow at the expected rate (failure to thrive), and general wasting and weight loss (cachexia).

Infantile systemic hyalinosis is also characterized by overgrowth of the gums (gingival hypertrophy). Additionally, people with this condition have joint deformities (contractures) that impair movement. Affected individuals may grow slowly and have bone abnormalities.

Although children with infantile systemic hyalinosis have severe physical limitations, mental development is typically normal. Affected individuals often do not survive beyond early childhood due to chronic diarrhea and recurrent infections.

How common is infantile systemic hyalinosis?

The prevalence of infantile systemic hyalinosis is unknown. Fewer than 20 people with this disorder have been reported.

What genes are related to infantile systemic hyalinosis?

Mutations in the ANTXR2 gene (also known as the CMG2 gene) cause infantile systemic hyalinosis. The ANTXR2 gene provides instructions for making a protein involved in the formation of tiny blood vessels (capillaries). Researchers believe that the ANTXR2 protein is also important for maintaining the structure of basement membranes, which are thin, sheet-like structures that separate and support cells in many tissues.

The signs and symptoms of infantile systemic hyalinosis are caused by the accumulation of a hyaline substance in different parts of the body. The nature of this substance is not well known, but it is likely made up of protein and sugar molecules. Researchers suspect that mutations in the ANTXR2 gene disrupt the formation of basement membranes, allowing the hyaline substance to leak through and build up in various body tissues.

How do people inherit infantile systemic hyalinosis?

Job Syndrome

noreply@blogger.com (Dallas Banks) — Mon, 22 Aug 2011 21:05:00 +0000

What is Job syndrome?

Job syndrome is a condition that affects several body systems, particularly the immune system. Recurrent infections are common in people with this condition. Affected individuals tend to have frequent bouts of pneumonia, which are caused by certain kinds of bacteria that infect the lungs and cause inflammation. Recurrent skin infections and an inflammatory skin disorder called eczema are also very common in Job syndrome. These skin problems cause rashes, blisters, collections of pus (abscesses), open sores, and scaling.

Job syndrome is characterized by abnormally high levels of an immune system protein called immunoglobulin E (IgE) in the blood, which is why this condition is also known as hyper-IgE syndrome. IgE triggers an immune response against foreign invaders in the body, particularly parasitic worms, and plays a role in allergies. It is unclear why people with Job syndrome have such high levels of IgE.

This condition also affects other parts of the body, including the bones and teeth. Many people with Job syndrome have skeletal abnormalities such as an unusually large range of joint movement (hyperextensibility), an abnormal curvature of the spine (scoliosis), reduced bone density (osteopenia), and a tendency for bones to fracture easily. Dental abnormalities are also characteristic of this condition. The primary (baby) teeth do not fall out at the usual time during childhood, but are retained as the adult teeth grow in. Other signs and symptoms of Job syndrome can include distinctive facial features and structural abnormalities of the brain, which typically do not affect a person's intelligence.

How common is Job syndrome?

This condition is rare, affecting fewer than 1 per million people. About 250 people with Job syndrome have been reported in the medical literature.

What genes are related to Job syndrome?

Mutations in the STAT3 gene cause Job syndrome. This gene provides instructions for making a protein that plays an important role in several body systems. The STAT3 protein is involved in many cellular functions, including cell growth and division, cell movement, and the self-destruction of cells (apoptosis). To carry out these roles, the STAT3 protein attaches to DNA and helps control the activity of particular genes.

Little is known about the effects of STAT3 mutations on the body's cells and tissues. Changes in this gene alter the structure and function of the STAT3 protein, impairing its ability to control the activity of other genes. The defective protein disrupts cellular functions such as immune system regulation. The resulting immune system abnormalities make people with Job syndrome highly susceptible to infections. The STAT3 protein is also involved in the formation of cells that build and break down bone tissue, which could help explain why STAT3 mutations lead to the skeletal and dental abnormalities characteristic of this condition.

When Job syndrome is not caused by STAT3 mutations, the genetic cause of the condition is unknown.

How do people inherit Job syndrome?

Job syndrome often has an autosomal dominant pattern of inheritance, which means one copy of an altered gene in each cell is sufficient to cause the disorder. In about half of all cases, an affected person inherits a STAT3 mutation from an affected parent. Other cases result from new mutations in this gene. These cases occur in people with no history of the disorder in their family.

Researchers have also described an autosomal recessive form of Job syndrome. Autosomal recessive inheritance means both copies of a gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition. The autosomal recessive form of Job syndrome is less common than the autosomal dominant form and has a different pattern of signs and symptoms. It is associated with fewer bacterial lung infections, more severe viral infections, serious complications involving the nervous system, and no skeletal or dental abnormalities. No STAT3 mutations have been found in people with the autosomal recessive form of this condition.