Gaucher disease is named after the French dermatologist, Phillipe Charles Ernest Gaucher, who in his 1882 MD thesis first described the phenotype today classified as type 1 (non-neuronopathic) Gaucher disease.
He reported primary and idiopathic hypertrophy of the spleen in a young woman, which he attributed to primary neoplasm. Neuronopathic forms of Gaucher disease (involving the CNS) were recognised later, type 2 in the early-to-mid 1920s and type 3 in 1959.1
Gaucher disease was appreciated as a disorder of metabolism as early as 1907.1 The major stored material was demonstrated to be glucosylceramide (also known as glucocerebroside) in 1934 but it wasn’t until 1964-1965 that the defective enzyme was identified.1,2 Gaucher disease was finally established as a lysosomal storage disorder in 1968, when the lysosomal localization of acid β-glucosidase was identified.1,2 The first mutation in the gene encoding acid β-glucosidase was only identified in 1987.1
Historical perspective of Gaucher disease classification
The current subtype classifications of Gaucher disease are based on earlier recognition of three broad phenotypic categories (infantile, juvenile and adult) that were considered to be distinct diseases, despite recognition that they share the same enzymatic defect. Phenotypes today classified as Gaucher disease type 1, which are characterized by visceral, haematologic, and skeletal manifestations and an absence of primary central nervous system (CNS) involvement, were considered to be an adulthood disease. Rapidly progressive disease with CNS involvement, typically resulting in death before the age of 2 years (Gaucher disease type 2), was referred to as infantile Gaucher disease. A third category, ‘juvenille’ Gaucher disease, encompassed patients with sub-acute or chronic disease with CNS involvement who survived infancy (Gaucher disease type 3).3,4
In common with the original sub-divisions, the current classification of Gaucher disease is based on the presence and/or absence and severity of primary, early-onset CNS disease.5 However, age-based distinctions were abandoned when it was realised they were inaccurate and misleading. Even today, the spectrum of Gaucher disease phenotypes has not been fully defined. The clinical picture of the disorder remains somewhat distorted by the small, mostly European-derived patient populations studied in the past.3