What is Fabry’s Disease
Fabry’s disease is a rare genetic disorder of lipid metabolism characterized by a deficiency of the enzyme alpha-galactosidase A, also known as ceramidetrihexosidase. The disorder belongs to a group of diseases known as lysosomal storage disorders. Lysosomes function as the primary digestive units within cells. Enzymes within lysosomes break down or digest particular nutrients, such as certain fats and carbohydrates. Absence or less than 1% of the alpha-galactosidase A enzyme results in the “classic” subtype of Fabry’s disease due to the abnormal accumulation of a substance consisting of fatty material and carbohydrates (i.e., glycolipids such as glycosphingolipid) in various organs of the body, particularly in the blood vessels. Symptoms of “classic” Fabry’s disease may include the appearance of clusters of wart-like discolorations on the skin (angiokeratomas), excruciating pain in the fingers and toes, and abdominal pain. Later in the course of the disease, kidney failure, heart disease, and/or strokes cause serious complications. Fabry’s disease, which is inherited as an X-linked trait, affects males and females. Males are more uniformly affected whereas females may be asymptomatic or severely affected as males due to “random X-inactivation.” Patients with alpha-galactosidase A levels greater than 1% of normal have a somewhat milder “later-onset” subtype of the disease.
Symptoms
-
Males
Typically, the disease begins in childhood with episodes of pain and burning sensations in the hands and feet. In addition, young patients often develop a spotted, dark red skin rash (angiokeratomas) seen most densely from the umbilicus to the knees, a decreased ability to perspire, and a characteristic change on the cornea of the eye which does not affect vision. The painful episodes may be brought on by exercise, fever, fatigue, stress, or change in weather conditions.The disease is slowly progressive and symptoms of kidney, heart and/or neurologic involvement usually occur between the ages of 30 to 45. Many patients are first diagnosed when the accumulated storage material begins to affect kidney or heart function. Therefore, it is important to annually monitor kidney function by blood and urine tests because kidney disease is a major complication that can occur in affected males.
A common heart symptom in Fabry patients is mitral valve prolapse, which is a benign condition that is present in approximately 10% of the normal population. More serious, but rarer, complications of Fabry disease include heart disease and strokes.
Other symptoms may include varying degrees of abdominal discomfort, frequent bowel movements shortly after eating, joint pain, back pain primarily in the kidney region or ringing of the ears (tinnitus).
-
Females
Females may show a wide range of clinical manifestations. Some individuals remain completely asymptomatic and have normal levels of a gal a while some are as severely affected as hemizygous males. This variability is most likely to be caused by random inactivation of one copy of the X-chromosome in each cell. The most common symptom of Fabry disease seen in heterozygous females is corneal dystrophy, which occurs in around 70% of females. Other symptoms that have been reported in females with Fabry disease include: angiokeratomas, acroparesthesias, anhidrosis, gastrointestinal disturbances, vascular lesions in the conjunctiva and retina, kidney disease, autonomic and other neurological complications such as tinnitus and vertigo, cardiovascular abnormalities, cerebrovascular abnormalities, fatigue. Women may often be misdiagnosed as having lupus or other conditions. -
Children
Although the signs and symptoms of Fabry disease generally appear during childhood, the diagnosis may often be missed. The earliest symptoms of Fabry disease in children are usually pain and angiokeratomas. The pain may, however, be dismissed as ‘growing pains’, while angiokeratomas may be overlooked during a routine clinical examination, particularly if they are confined to locations such as the backs of the ears. Cardiac and renal involvement can also begin in childhood, thus early diagnosis and careful monitoring are necessary. Other symptoms include Hypohidrosis (inability to sweat), GI symptoms that mimic chronic inflammatory bowel disease, recurrent nausea and vomiting, vertigo, tinnitus, headaches, fevers.
[/list]
Treatments
Pain associated with Fabry disease can be difficult to treat but usually responds to medications such as Tegretol (carbamazepine), Dilantin or Neurotin. Metoclopramide, Lipisorb (a nutritional supplement), Pancrelipase may be beneficial in treating Gastrointestinal hyperactivity. Early experiments with enzyme replacement therapy indicate promising results.
[/list]
