Fabry Disease

At a glance

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.

Synonyms

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

Incidence

Second most prevalent metabolic storage disorder. ☞Gaucher Disease is the most prevalent medical condition with similar condition as observed with Fabry’s Disease. The incidence is reported to be approximately 1:117,000 live births.

Genetic inheritance

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

Pathophysiology

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

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

Clinical aspects

The main features of the disease are linked to the deposit of glycolipids (Gb³) in the vascular endothelium, smooth muscle cells, renal epithelium, myocardium, dorsal root ganglia, autonomic nervous system, and the brain. Clinically, it is associated with cerebral strokes, 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 is frequent in both hands and feet as a result of progressive neuropathy. Skeletal involvement causes arthralgia, articular erosion, avascular necrosis, and limitation of the temporomandibular joint. As the disease evolves, the lungs become involved and pulmonary function tests confirm the presence of an obstructive ventilator disease. Finally, the characteristic presence of angiokeratomas on the skin, mucous membranes, corneal abnormalities, as well as the absence of sweating capabilities define this medical condition.

Precautions before anesthesia

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.

Anesthetic considerations

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 ...