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.
Angiokeratomata on the eyelids in a patient with Fabry disease.
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, ...