Fabry disease, a lysosomal storage disease, is an X-linked condition caused by α-galactosidase (α-Gal A) deficiency resulting in progressive accumulation of globotriaosylceramide (GL-3) in the lysosomes. Fabry disease ranges from the severe classic form to atypical forms. The classic form is most common. Atypical, late-onset forms may be missed to diagnosis.
Symptoms of the classic form usually occur in childhood or adolescence with periodic episodes of severe pain in the extremities (acroparathesias), vascular cutaneous lesions (angiokeratomas), sweating abnormalities, characteristic corneal and lenticular opacities, and proteinuria. Renal insufficiency leading to end-stage renal disease (ESRD) usually occurs in the third to fifth decade of life. Renal disease, cardiac involvement, and/or cerebrovascular disease are the leading causes of death.
The atypical form has later onset, in the sixth to eighth decades of life, and usually results in left ventricular hypertrophy or other cardiac problems such as mitral insufficiency and/or cardiomyopathy. Renal manifestations may or may not be present, but the characteristic skin lesions and acroparathesias are not observed in the atypical form.
Females are typically more mildly affected than males though have been observed with a wide range of presentations, from absence of symptoms to effects as severe as those seen in males. The variable expressivity is attributed to random X-inactivation in female heterozygotes.
This laboratory performs Sanger sequencing of the GLA gene.