Type 2 Gaucher disease: phenotypic variation and genotypic heterogeneity

Abstract

Gaucher disease (GD), the most common lysosomal storage disease, results from a deficiency of the lysosomal enzyme glucocerebrosidase. GD has been classified into 3 types, of which type 2 (the acute neuronopathic form) is the most severe, presenting pre- or perinatally, or in the first few months of life. Traditionally, type 2 GD was considered to have the most uniform clinical phenotype when compared to other GD subtypes. However, case studies over time have demonstrated that type 2 GD, like types 1 and 3, manifests with a spectrum of phenotypes. This review includes case reports that illustrate the broad range of clinical presentations encountered in type 2 GD, as well as a discussion of associated manifestations, pathological findings, diagnostic techniques, and a review of current therapies. While type 2 GD is generally associated with severe mutations in the glucocerebrosidase gene, there is also significant genotypic heterogeneity.

Figure 1

Two patients with symptoms of type 2 Gaucher disease, including (A) collodion skin, and (B) abdominal protrusion, due to hepatosplenomegaly, and opisthotonus

Figure 2

The structure of the gene for human β-glucocerebrosidase (GBA) is shown, depicting is the 62-kb region surrounding GBA along chromosome 1q, with known genes and pseudogenes and their transcription directions. C1orf2, chromosome 1 open reading frame 2 (cote1); GBA, glucocerebrosidase; MTXP, metaxin 1 pseudogene; GBAP, glucocerebrosidase pseudogene; MTX1, metaxin 1; THBS3, thrombospondin 3.