Fabry Disease

Genetically transmitted lysosomal storage disorder caused by a deficiency in α-galactosidase and characterized by an accumulation of substrate in many organs and tissue resulting in progressive neurologic and vascular degeneration.

(Figure)

Angiokeratoma Corporis Diffusum; Anderson-Fabry Disease; Alpha-Galactosidase A Deficiency.

Second most prevalent metabolic storage disorder. Gaucher disease being the most prevalent. Incidence is 1:117,000 live births.

Transmission is recessive and X-linked. Men are affected, but women carriers can present symptoms of the disease.

Lack of α-galactosidase A leads to intracellular accumulation of its substrate globotriaosylceramide. This defect leads to severe painful neuropathy with progressive renal, cardiovascular, and cerebrovascular dysfunction and finally death.

Diagnosis is clinical and biochemical. The clinical signs indicating Fabry disease are the presence of angiokeratomas in the skin and mucous membrane and benign corneal abnormalities. Diagnosis is confirmed by white blood cells or cultured skin fibroblasts showing a decreased α-galactosidase A activity. Treatment is symptomatic.

The main features of the disease are caused by the deposit of the glycolipid (Gb3) in the vascular endothelium, smooth muscle cells, renal epithelium, myocardium, dorsal root ganglia, autonomic nervous system, and brain. Clinically, it translates into stroke, progressive renal failure with proteinuria, cardiac hypertrophy, arrhythmias, valvular insufficiency, and myocardial infarction. Other manifestations of the disease are progressive sensorineural hearing loss, vertigo, postprandial abdominal cramps, and achalasia. Pain in the hands and feet as a result of neuropathy is common. Skeletal involvement translates to arthralgia, articular erosion, avascular necrosis, and limitation of the temporomandibular joint. As the disease evolves, the lungs become involved and pulmonary function tests show an obstructive disease. Finally, they present characteristics of angiokeratomas in the skin and mucous membranes, corneal abnormalities, and a lack of sweating.

Because it is a multisystemic disease, all major systems must be evaluated thoroughly. The patient should undergo a cardiac evaluation with an ECG and echocardiogram, pulmonary function tests, and renal function tests. If the patient has symptoms of achalasia, he/she should be given sodium citrate as a gastric prophylaxis before undergoing a general anesthetic.

Because of the disseminated vascular involvement in the major organs, aim at preventing important shifts in blood pressure, particularly hypotension, and ensure phenylephrine is available. The ECG should be monitored for the presence of arrhythmias. Signs of cardiac involvement because of the disease should be managed accordingly. Direct laryngoscopy may be more difficult because of limited mouth opening as a consequence of temporomandibular joint stiffness.

In the presence of arrhythmias, avoid using halothane; however, halothane is the drug of choice in the presence of cardiac hypertrophy. Anticholinergic drugs can worsen the hypohidrosis and are best avoided. If renal function is decreased, drugs eliminated by this route, such as neuromuscular relaxants and antibiotics, should be avoided or their dosage adjusted.