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Article Date: 12 Jul 2013 - 21:00 PDT Current ratings for:
What Is Fabry Disease? What Causes Fabry Disease?
Fabry disease is a rare, inherited disease caused by the deficiency of an enzyme called alpha galactosidase A (a-GAL A), which is encoded by the GLA gene. In patients with Fabry disease, a-GAL A is either lacking or deficient. The disease is also known as Anderson-Fabry disease, alpha-galactosidase A deficiency, or angiokeratoma corporis diffusum.
A genetic fault (mutation) in the gene that controls a-GAL A causes a poor breakdown of lipids, which leads to a harmful accumulation of lipids - specifically globotriaosylceramide (GL-3) - in the cardiovascular system, autonomic nervous system, kidneys and eyes.
There are several lipid storage disorders; Fabry disease is the only X-linked (inherited) one.
Fabry disease is estimated to affect 1 in every 55,000 males. Many more males have the defective gene, but with no symptoms.
The mutated gene is carried on the mother's X chromosome, meaning there is a 50% chance she will pass it on to her sons, and a 50% risk her daughters will be carriers.
If females do have symptoms, they tend to be much milder than those seen in males. However, some females with Fabry disease may be affected severely. Young boys may have serious eye manifestations, particularly cloudiness of the cornea.
The accumulation of lipids, specifically GL-3, can lead to problems with arterial circulation and a higher risk of stroke or heart attack.
A study published in the International Journal of Clinical Practice found that Spanish patients with Fabry disease react differently to those in the rest of Europe.
Fabry disease may be hard to detect because several of its signs and symptoms overlap those present in other diseases and conditions. Patients do not typically have all of the symptoms associated with Fabry, while others may develop them at different times throughout their lives.
It is important that the doctor finds out whether there is a family history of Fabry disease whenever it is suspected.
Angiokeratoma
Signs and symptoms usually start during childhood.
Pain - the child experiences episodes of discomfort and pain in the hands and feet (acroparesthesias). These can be triggered by stress, fatigue, fever, physical activity, and even changes in the weather.Skin rash - known as angiokeratoma, A dark, red, spotted skin rash appears. The rash is seen most densely between the navel (belly button) and the knees.
Hypohidrosis - reduced ability to sweat.
Keratopathy - clouding of the corneas. This does not affect vision
Fabry disease usually develops slowly over many years as GL-3 gradually accumulates. After the age of 30 years, patients may experience:
Gastrointestinal problems - patients with Fabry disease commonly experience stomach problems, which may include nausea, vomiting, and diarrhea.Cardiovascular problems - years of GL-3 accumulation eventually result in damage to blood vessels that supply the heart, as well as damage to the heart itself. Problems include:
- heart failure
- arrhythmia
- heart attack
- faulty heart valves
- enlarged heart
Renal (kidney) problems - decades of GL-3 accumulation can lead to renal failure or renal insufficiency. Often, Fabry disease is first detected when the patient comes to the doctor with kidney problems.
CNS (central nervous system) disorders - small blood vessels in the brain can become affected after years of GL-3 buildup. Patients are at a higher risk of having:
- stroke
- dizziness
- numbness and tingling (pins and needles)
- headaches
- weakness
Hearing problems - for the same reasons, GL-3 accumulation, the patient may gradually lose his hearing, or experience ringing in the ears (tinnitus).
Emotional and psychological problems - living with the symptoms associated with Fabry disease, many of which get worse with time, causes anxiety, fear, and also depression. There may be a feeling of guilt if the disease is inherited by an offspring.
Females, who are also carriers of the genetic mutation, generally either have no symptoms or much milder ones than males. However, a small percentage may suffer as much as their male counterparts.
In milder cases, symptoms usually appear during the patient's childhood/teen years, and may include skin rashes, corneal cloudiness, pain in the extremities, and hypohidrosis. There is also the possibility of chronic diarrhea and abdominal pain. As they get older the left side of the heart may become enlarged (left ventricular hypertrophy); there is also a possibility of heart-valve problems.
In more serious cases, the girl/woman has the same signs and symptoms as males with severe symptoms.
The doctor may suspect Fabry disease if the patient has the associated signs and symptoms. If one of the patient's relatives is found to have the disease, the physician will order a blood test to measure a-GAL A activity.
Screening females for Fabry disease is not so simple, because the blood test can be misleading, due to the random nature of X-inactivation, i.e. the faulty gene may be switched off, so the enzyme a-GAL A won't be affected. A chromosomal analysis of the GLA gene is much more accurate than a blood test.
If excessive GL-3 accumulation is detected, a kidney biopsy may help.
Fabry disease is commonly misdiagnosed by pediatricians and internists.
Doctors say that prevention is the first level of treatment for patients with Fabry disease.
Pain and discomfort - episodes of pain are nearly always linked to certain triggers, such as exposure to heat, temperature changes, sun exposure, exercise, and fever. The patient must learn to avoid these pain triggers.For patients with severe and frequent episodes of pain, the doctor may prescribe an anticonvulsant, such as carbamazepine (Tegretol, Tegretol XR , Equetro, Carbatrol) or diphenylhydantoin (Dilantin). They should be taken daily.
Enzyme replacement therapy (ERT) - ERT is a medical treatment that replaces an enzyme which is either absent or deficient in patients. In Fabry disease patients' cases, the missing enzyme is alpha galactosidase A (a-GAL A).
There are two recombinant GLA preparations for ERT on the market today: 1. agalsidase alfa (Replagal, Shire Human Genetic Therapies, Cambridge, MA, 0.2 mg/kg per infusion). 2. agalsidase beta (Fabrazyme, Genzyme Corporation, Cambridge, MA, 1 mg/kg per infusion).
In the USA, only Fabrazyme is FDA approved. Genzyme Corp. writes on its website "The lowering of GL-3 suggests that Fabrazyme may improve how Fabry disease affects your body; however a relationship of lower GL-3 to specific signs and symptoms of Fabry disease has not been proven."
ERT has one serious drawback - it is extremely expensive.
The other complications related to Fabry disease, such as skin, heart, kidney and psychological problems are treated separately as they occur, by specialist doctors, i.e. if it is a heart problem, the patient will be treated by a cardiologist.
Patients who are diagnosed early and can receive treatments promptly have longer lifespans. According to the Genzyme Corporation, new treatments have lengthened life expectancy from 41 to 50 years.
Researchers published an article in Genetics in Medicine saying that "The life expectancy of males with Fabry disease was 58.2 years, compared with 74.7 years in the general population of the United States. The life expectancy of females with Fabry disease was 75.4 years, compared with 80.0 years in the United States."
In the video below Darren Bidulka talks about living with Fabry disease. This is from a collection of 9 videos on Fabry disease
Written by Christian Nordqvist
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today
MLA
14 Jul. 2013.
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'What Is Fabry Disease? What Causes Fabry Disease?'
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