2.1 Fabry disease is an inherited lysosomal storage disease caused by a non-functional or only partially functional enzyme, alpha-galactosidase A (alpha‑gal A). Decreased activity of alpha-gal A in lysosomes results in the accumulation of enzyme substrates (Gb3 and lyso‑Gb3) which cause cellular damage in tissues throughout the body.
2.2 Symptoms include pain that spreads through the body (called a Fabry crisis), gastrointestinal complications, headaches, impaired sweating, vertigo and hearing impairment. The age of onset, severity and progression of Fabry disease is variable. Accumulation of Gb3 in lysosomes leads to irreversible organ damage, resulting in progressive kidney and heart disease and increased risk of stroke at a relatively young age. Fabry disease can have a profound impact on health-related quality of life and can reduce life expectancy. The company estimates that there are 855 people with Fabry disease in England, suggesting a prevalence of approximately 0.002%. The company estimated that there are around 142 people for whom migalastat may be an appropriate option.
2.3 There is no cure for Fabry disease. Current treatment options are infusions with enzyme replacement therapy (ERT; agalsidase alfa or agalsidase beta) every 2 weeks, or supportive care to manage the symptoms and complications. ERT is a lifelong treatment that reduces symptoms and slows disease progression. In England, 8 highly specialist lysosomal storage disorder centres (5 adult centres and 3 paediatric centres) diagnose, assess and treat patients.