Gaucher disease (GD) encompasses a continuum of clinical findings from a perinatal lethal disorder to an asymptomatic type. The identification of three major clinical types (1, 2, and 3) and two other subtypes (perinatal-lethal and cardiovascular) is useful in determining prognosis and management. GD type 1 is characterized by the presence of clinical or radiographic evidence of bone disease (osteopenia, focal lytic or sclerotic lesions, and osteonecrosis), hepatosplenomegaly, anemia and thrombocytopenia, lung disease, and the absence of primary central nervous system disease. GD types 2 and 3 are characterized by the presence of primary neurologic disease; in the past, they were distinguished by age of onset and rate of disease progression, but these distinctions are not absolute. Disease with onset before age two years, limited psychomotor development, and a rapidly progressive course with death by age two to four years is classified as GD type 2. Individuals with GD type 3 may have onset before age two years, but often have a more slowly progressive course, with survival into the third or fourth decade. The perinatal-lethal form is associated with ichthyosiform or collodion skin abnormalities or with nonimmune hydrops fetalis. The cardiovascular form is characterized by calcification of the aortic and mitral valves, mild splenomegaly, corneal opacities, and supranuclear ophthalmoplegia. Cardiopulmonary complications have been described with all the clinical subtypes, although varying in frequency and severity. [from GeneReviews, Gaucher Disease, PMID:20301446 2016.3.28]

Gaucher disease is classically categorized phenotypically into 3 main subtypes: nonneuronopathic type I (MIM:230800), acute neuronopathic type II (MIM:230900), and subacute neuronopathic type III (MIM:231000). Type I is the most common form of Gaucher disease and lacks primary central nervous system involvement. Types II and III have central nervous system involvement and neurologic manifestations (Jmoudiak and Futerman, 2005; pubmed:15813845)). There are 2 additional phenotypes which may be distinguished: perinatal lethal Gaucher disease (MIM:608013), which is a severe form of type II, and Gaucher disease type IIIC (MIM:231005), which also has cardiovascular calcifications.

[from MIM:230800, 2016.3.28]

Gaucher disease is a lysosomal storage disease characterized by an accumulation of glucocerebrosides. [NCBI Gene: 2629, GBA; 2017.07.14]

The lipid glucosylceramide (GlcCer) accumulates in tissues in Gaucher disease. GlcCer-laden macrophages are known as ‘'Gaucher cells’', which are the classical hallmark of the disease (Jmoudiak and Futerman, 2005; pubmed:15813845). [from MIM:230800, 2016.3.28]

GBA encodes a lysosomal membrane protein that cleaves the beta-glucosidic linkage of glycosylceramide, an intermediate in glycolipid metabolism. Mutations in this gene cause Gaucher disease, a lysosomal storage disease characterized by an accumulation of glucocerebrosides (also called glucosylceramide (GlcCer), glucosylcerebroside). [from Gene Cards, GBA, 2016.3.28]

The unfolded protein response is activated in skin fibroblasts derived from Gaucher disease patients and in flies expressing mutant GBA orthologs and in transgenic flies carrying Gaucher disease-associated mutations in the human GBA gene (Maor et al. 2013).

Gaucher disease due to deficient activity of acid beta-glucosidase (also called glucocerebrosidase, GlcCerase, or glucosylceramidase). As a result of this deficiency, there is intracellular accumulation of glucosylceramide (GlcCer, glucosylcerebroside) in lysosomes, primarily within cells of mononuclear phagocyte origin. GlcCer is an importantconstituent of biological membranes and is a key intermediate in the biosynthetic and degradative pathways of complex glycosphingolipids (Jmoudiak and Futerman, 2005; pubmed:15813845). [from MIM:230800, 2016.3.28]