Fabry disease was first described in 1898 by two independent dermatologists, William Anderson and Johannes Fabry. They each described patients with reddish purple maculopapular skin lesions, or ‘angiokeratoma corporis diffusum’, today recognised as characteristic of Fabry disease.1 The underlying cause of the disease, α-galactosidase A deficiency and substrate accumulation, was discovered in 19672.
Other symptoms and hereditary aspects of Fabry disease were described in the decades that followed, but it wasn’t until 1959 that the disease was first recognised as a hereditary disorder of lipid metabolism.3 The X-linked inheritance pattern of Fabry disease was recognised in 1965, followed two years later by identification of α-galactosidase A deficiency and substrate accumulation as the underlying cause of the clinical manifestations.3
Our understanding of Fabry disease has developed with the recognition of individuals with GLA gene mutations and clinical manifestations confined predominantly to a single organ. These so-called ‘atypical variants’ were first detected among patients with late-onset cardiac or cardiopulmonary disease and patients receiving renal dialysis.4 The sub-classifications ‘cardiac variant’ and ‘renal variant’ were introduced to describe these single-organ phenotypes of Fabry disease.5
The clinical manifestation of Fabry disease in women has long not been recognised. Heterozygous females were considered to be asymptomatic carriers of the mutant gene as recently as 2001, and statements that underestimate their burden of disease still appear in medical literature.6-8 Misconceptions were long upheld by the notion of Fabry disease as an X-linked recessive trait. The term ‘X-linked inheritance’ is now favoured to describe the inheritance pattern of Fabry disease.5,6 In the past, female heterozygotes were referred to as ‘carriers’ but today it is recommended that the term be avoided as it is misleading.7