Inheritance: X-linked recessive, with affected patients hemizygous (female homozygotes theoretically possible but very unlikely)
Possible patient types:
(1) classic disease in a male, with onset in childhood and premature death as an adult (affect 1 in 40,000 male births)
(2) variant disease in a male (mild to moderate disease, associated with some enzyme activity)
(3) variant disease in female (ranges from asymptomatic to classic disease)
Typical features in "classic" disease:
(1) severe, intermittent pain in the extremities
(2) angiokeratomas (telangiectasias or angiomas with overlying hyperkeratosis)
(3) corneal and/or lenticular opacities
(4) hypohydrosis (decreased ability to sweat)
(5) intolerance to heat, cold and exercise
(6) renal insufficiency with proteinuria progressing to renal failure
(7) left ventricular hypertrophy progressing to congestive heart failure, cardiac arrhythmias, and myocardial infarction
(8) premature cerebrovascular disease with transient ischemic attacks and early stroke
(9) episodic diarrhea and abdominal pain
(10) biopsy show lipid laden cells, especially in endothelium, histiocytes, ganglion cells and some epithelial cells. This material is birefringent under polarized light with a "Maltese cross" pattern.
Confirmation:
(1) deficient alpha-galactosidase A activity in plasma, leukocytes or tears
(2) increased globotriaosylceramide in plasma or urine sediment
