Metabolic defect: glucocerebrosidase deficiency Other sphingolipid degradation diseases: acid sphingomyelinase deficiency | Fabry | Farber | Gaucher: type II, type III | GM1 gangliosidosis: type I, type II, type III | Tay-Sachs: type I, type II, type III | Sandhoff: type I | Krabbé | metachromatic leukodystrophy: type I, type II, type III

Current page: Gaucher - type I Select Another Disease Select disease Acid sphingomyel. def. Aspartylglycosaminuria Cystinosis Fabry disease Farber disease Fucosidosis type I Fucosidosis type II Galactosialidosis Gaucher type I Gaucher type II Gaucher type III GM1 gangliosidosis I GM1 gangliosidosis II GM1 gangliosidosis III Infantile sialic acid Krabbé disease Mannosidosis Metachr. leukodys. I Metachr. leukodys. II Metachr. leukodys. III MPS I MPS II Hunter MPS III Sanfilippo MPS IV Morquio MPS VI Maroteaux-Lamy MPS VII Sly Mucolipidosis II Mucolipidosis III Mucolipidosis IV Neuro ceroid lipof I Neuro ceroid lipof II Neuro ceroid lipof III Neuro ceroid lipof IV Pompe disease Pycnodysostosis Salla disease Sandhoff type I Sialidosis type I Sialidosis type II Tay-Sachs type I Tay-Sachs type II Tay-Sachs type III

Enzyme deficiency results in accumulation of un-degraded glycolipid substrates, particularly glucocerebroside, within the lysosomes of macrophages. Accumulation of Gaucher cells (enlarged cells containing excess glucocerebroside) in organs and tissues results in multi-systemic manifestations.

Hepatosplenomegaly		Skeletal abnormalities (Erlenmeyer flask deformity)

In Gaucher disease, a deficiency of the enzyme glucocerebrosidase leads to the accumulation of the lipid glucocerebroside within the lysosomes of the monocyte-macrophage system. Lipid-engorged cells with eccentric nuclei, known as Gaucher cells, accumulate and displace healthy normal cells in bone marrow and visceral organs, causing a host of signs, including skeletal deterioration, anemia, hepatosplenomegaly, and organ dysfunction. In rare cases Gaucher cells affect the brain and nervous system. Resulting symptoms can vary from mild to severe and appear at any time, from infancy to adulthood.

Type I is most common form, with variable age of onset of symptoms

Variable systemic symptoms

No central nervous system involvement

Normal life expectancy (2% have a fulminant course)

Incidence: pan-ethnic, but higher frequency among Ashkenazi Jews; 1 in 40-60,000 live births
Diagnosis: enzyme assay

Splenomegaly (most common symptom in all three types of Gaucher)

Hypersplenism contributing to pancytopenia

Mechanical interference with bowel, kidney, diaphragm or circulation

Hepatomegaly (usually asymptomatic but may be complicated by liver failure with portal hypertension, cirrhosis, esophageal varices; bleeding can occur infrequently)

Replacement of bone marrow with Gaucher cells (contributing to anemia, leukopenia, thrombocytopenia)

Bone pain

Femoral head necrosis

Pathologic fractures - femoral neck, long bones

Collapse of vertebral bodies with spinal cord compression or thoracic kyphosis

"Bone crisis" (bone infarction)

Hypoxia (due to liver disease and pulmonary infiltration)

Restrictive lung disease (due to hepatosplenomegaly and kyphosciolosis)

Pulmonary hypertension

Pulmonary function abnormalities

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Interstitial myocardial infiltration

Restrictive pericarditis

Calcification of valves

Yellow-brown pigmentation

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1. Grabowski GA. Lysosomal storage diseases. In: Braunwald E, Fauci AS, eds. Harrison's Principles of Internal Medicine. 15th ed. New York, NY: McGraw-Hill; 2001:2276-2281.

2. Cox TM, Schofield JP. Gaucher's disease: clinical features and natural history. In: Baillieres Clin Haematol; 1997. p. 657-89.