History of Fabry Disease


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


  1. 1.Fabry H. (2001) An historical overview of Fabry disease. J Inherit Metab Dis 24 Suppl 2: 3-7.
  2. 2.Brady RO, Gal AE, Bradley RM, Martensson E, Warshaw AL, Laster L. Enzymatic defect in Fabry's disease. Ceramidetrihexosidase deficiency. N Engl J Med. 1967;276:1163–7.
  3. 3.Fabry H. (2002) Angiokeratoma corporis diffusum--Fabry disease: historical review from the original description to the introduction of enzyme replacement therapy. Acta Paediatr Suppl 91(439): 3-5.
  4. 4.Desnick RJ, Ioannou YA, Eng CM. α-Galactosidase A Deficiency: Fabry Disease. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, et al., editors. The Online Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGra
  1. 5.Germain DP. (2010) Fabry disease. Orphanet J Rare Dis 5: 30.
  2. 6.Wang RY, Lelis A, Mirocha J, Wilcox WR. (2007) Heterozygous Fabry women are not just carriers, but have a significant burden of disease and impaired quality of life. Genet Med 9(1): 34-45.
  3. 7.Laney DA, Fernhoff PM. (2008) Diagnosis of Fabry disease via analysis of family history. J Genet Couns 17(1): 79-83.
  4. 8.Deegan PB, Bähner F, Barba M, Beck M. Fabry disease in females: clinical characteristics and effects of enzyme replacement therapy. In: Mehta A, Beck M, Sunder-Plassmann G, editors. Fabry Disease: Perspectives from 5 Years of FOS. Oxford PharmaGenesis; 2006.