Fabry disease (Anderson-Fabry disease) is a rare disease caused by a deficiency in the enzyme ceramide trihexosidase (α-galactosidase A). Fabry disease is also known by its alternative descriptive name, angiokeratoma corporis diffusum. It is inherited in an X-linked recessive pattern and is classified as a lysosomal storage disease. The defect in this enzyme causes a lack of proper metabolism of globotriaosylceramide (ceramide trihexoside) and accumulation of this lipid in various tissues throughout the body. Fabry disease affects the skin, kidneys, cardiovascular system, eye, and neurological system. There is no known cure, but advances in enzyme replacement therapy have shown promising results. Males are more severely affected; females can be affected to varying degrees or can act as carriers of the disease. Fabry disease has been estimated to occur in 1 of every 50,000 males. There is an increase in the mortality rate, with the average age at death for a man with classic Fabry disease being 40 years.
Clinical Findings: The clinical manifestations of Fabry disease have a slow onset during childhood; the average age at onset is 5 to 6 years. Acroparesthesias are the initial presenting symptoms in most children. Patients have severe pain in the hands and feet that is episodic in nature and can last from minutes to hours or, in extreme cases, days. The pain is often described as a burning sensation. Episodes of stress can induce the acroparesthesias. This is accompanied by bouts of hypohidrosis or, less commonly, anhidrosis. This inability to sweat properly may lead to heat exhaustion and heat intolerance. Patients also eventually develop varying degrees of hearing loss.
The cutaneous findings consist of numerous angio- keratomas in unusual locations. These fine, red, hyper- keratotic papules occur on the trunk and lower extremities and are almost always located between the umbilicus and the knees. The number of angiokeratomas continues to increase with time, eventually reaching hundreds to thousands. The mucous membranes may also be involved with angiokeratomas. Presentation of a child or a young adult with multiple angio- keratomas should prompt the clinician to consider the diagnosis of Fabry disease and to search for any other symptoms consistent with the disease. If the diagnosis of Fabry disease is made, patients should be referred to a specialty center that cares for these patients.
The most characteristic ocular finding is that of cornea verticillata. This is a whorl-like corneal opacity that can be observed only by slit-lamp examination. They do not impede vision.
With time, patients begin to develop progressive kidney disease. The earliest sign is often asymptomatic proteinuria. Continued kidney damage eventually leads to chronic renal failure and end-stage renal disease. Maltese cross shaped deposits are often found in the urine sediment from patients with Fabry disease and represent lipid accumulations. Cardiovascular changes can be seen and lead to ischemic heart disease. Stroke and cerebral vascular disease are common and cause a significant amount of mortality in these patients.
The diagnosis of Fabry disease can be made by evaluating the plasma for α-galactosidase A activity. Males with classic Fabry disease have less than 1% of proper enzyme activity. DNA gene sequencing can be performed to isolate the exact genetic defect. Genetic testing is the only reliable way to diagnosis females with the disease, because female carriers do have some plasma enzyme activity.
Treatment: Many medications can be used to treat the acroparesthesias, and they typically come from the antiseizure class of medications. Phenytoin and gabapentin are used to help control the frequency and duration of the episodes. In the past, there were no specific therapies for Fabry disease. End-stage renal disease often required kidney transplantation. Enzyme replacement therapy has been available since 2003 and has begun to have an impact on morbidity in these patients. Long-term studies are needed to make any conclusions regarding their effects on mortality.