Fabry Disease

Fabry disease is an X-linked lysosomal storage disorder caused by deficient alpha-galactosidase A activity. The missing enzyme allows GL-3 (Gb3) and lyso-Gb3 to accumulate progressively in vascular endothelium, podocytes, renal tubules, cardiomyocytes and neurons. The result is not a single-organ kidney disease: renal injury, left ventricular hypertrophy, cerebrovascular disease, neuropathic pain, gastrointestinal symptoms and impaired sweating may emerge in different combinations. The clinical pattern depends partly on residual enzyme activity. Classic disease usually begins in childhood or adolescence with burning pain in the hands and feet, angiokeratomas, hypohidrosis and corneal verticillata before progressive kidney and cardiac injury. Later-onset disease may first appear in adulthood as otherwise unexplained left ventricular hypertrophy, renal insufficiency or stroke, without the childhood skin and pain findings. A female patient cannot be reassured by the word “carrier” or by a normal enzyme result: random X-chromosome inactivation can leave heterozygous females anywhere from asymptomatic to severely affected. For a Canadian NP, the diagnostic trigger is an unexplained combination of CKD, proteinuria, hypertrophic cardiomyopathy-like findings, young-onset stroke, small-fibre neuropathy or heat intolerance. Confirmation should lead to coordinated care...