Signs and symptoms
Signs and symptoms of Fabry disease arise from lysosomal globotriaosylceramide (GL3) accumulation affecting the nervous system, kidneys, heart, gastrointestinal tract, skin, eyes and cerebral vasculature.1
Pain with onset in childhood, cornea verticillata, angiokeratomas, and anhidrosis or hypohidrosis are early hallmark features of classical Fabry disease.1
Progressive organ damage develops with age, with significant renal, cardiac and cerebrovascular complications typically occurring after the age of 20 years in classically affected individuals.2 The predominance of renal, cardiac and cerebrovascular disease differs among patients as progression in different organ systems occurs independently.3 The morbidity and mortality associated with these complications limits the life-expectancy of untreated males to approximately 50 years, and untreated females to 70 years.2 End-stage renal disease, cerebrovascular or cardiovascular complications are common causes of death.1,3
Characteristic signs and symptoms of Fabry disease are often absent in patients with atypical forms of the disorder.4,5 These individuals usually have milder disease and delayed presentation of symptoms arising from predominantly single-organ involvement.2
Recognising Fabry disease in clinical practice is challenging. The disease presentation is heterogeneous and some early signs and symptoms of Fabry disease have an extensive differential diagnosis.
Accumulation of α-galactosidase A substrates over time triggers a cascade of events leading to secondary disease processes. Progressive damage to vital organ systems leads to significant renal, cardiac and cerebrovascular complications.
A wide range of signs and symptoms are observed in Fabry disease due to the storage of GL3 in a variety of cell types.