Gaucher Disease



Most common sphingolipidosis (a group of lysosomal storage disorders)

Glucocerebrosidase deficiency

GBA1 Gene mutation




Autosomal recessive inheritance of mutations in the GBA1 gene

Deficiency of glucocerebrosidase leads to accumulation of its substrate, glucosylceramide, in macrophages/monocytes —> formation of abnormal ‘Gaucher cells’




1/800 Ashkenazi Jews

1/40,000-60,000 General population


Clinical Features


Huge variability - May be asymptomatic throughout life, or present in early childhood


Cytopenias, hepatomegaly and massive splenomegaly caused by infiltration with Gaucher cells

Fatigue, growth restriction, delayed puberty, acute bone pains, osteoporosis, avascular necrosis, gallstones, pulmonary hypertension, neurological impairment


Splenomegaly, present in 90%, may be the only clinical sign


Type 1 (up to 90% of cases) – Mostly effects the viscera. Predisposed to Parkinson’s disease

Type 2 – Severe neurological impairment, hydrops fetalis

Type 3 – Variable neurological impairment, horizontal ophthalmoplegia





Enzyme activity – acid glucocerebrosidase activity in leukocytes (10-15% of normal values)

Genetics – genome sequencing (>300 different mutations described)


BM aspirate – not indicated for diagnosis of Gaucher, but is often performed due to presenting features of cytopenias / organomegaly and is likely to demonstrate Gaucher cells.


Disease biomarkers (response to treatment):

Chitotriosidase levels

CCL18 levels




IV Enzyme Replacement Therapy – imiglucerase, velaglucerase, taliglucerase

PO Inhibitors of glucosylceramide synthesis – miglustat, eliglustat


(Pseudo-Gaucher Cells)


Caused by histocytic accumulation of immunoglobulin crystals, and seen in myeloma, waldenstroms, CML and MDS.