Overview
Definition
An X-linked lysosomal storage disease characterized by alpha-galactosidase A deficiency, causing globotriaosylceramide accumulation in blood vessels and organs.
Epidemiology
Prevalence ~1 in 40,000 males.
Etiology & Risk Factors
- GLA gene mutations
- Accumulation of Gb3 in endothelial and vascular smooth muscle cells
Clinical Symptoms
- Neuropathic limb pain (acroparesthesias)
- Angiokeratomas (small dark red spots on skin)
- Hypohidrosis (decreased sweating)
- Corneal verticillata
Clinical Approach
Diagnosis
- Low alpha-galactosidase A activity (males)
- Genetic testing for GLA mutations
Management
- Enzyme Replacement Therapy (Agalsidase beta)
- Chaperone therapy (Migalastat) for amenable mutations
- ACE inhibitors for proteinuria
Complications
- End-stage renal disease
- Hypertrophic cardiomyopathy / Arrhythmias
- Premature stroke