Lipid Storage Disorder: Gaucher Disease

I. Epidemiology & Pathogenesis

Caused by deficiency of acid β-glucosidase, also known as Glucocerebrosidase, a lysosomal enzyme that breaks down glucosylceramide into glucose and ceramide. (GBA1 gene)
Incidence: ~1 in 50,000 live births; up to 1 in 855 in Ashkenazi Jews
Most common lipid storage disorder
Glucosylceramide accumulates in macrophages from turnover of leukocytes, erythrocytes, and platelets
Gaucher cells: engorged macrophages with tubular inclusions resembling “wrinkled tissue paper”
Gaucher cells trigger inflammation and fibrosis

Type 1 (nonneuronopathic): Most common; onset from childhood to adulthood; organomegaly, bone and lung disease
Type 2 (acute neuronopathic): Onset within 3 months; organomegaly, eye movement abnormalities, seizures; death by age 2–4
Type 3 (chronic neuronopathic): Slowly progressive neurological symptoms; variable onset; organomegaly and skeletal issues
Other forms: perinatal-lethal and cardiovascular variants
Hepatosplenomegaly is nearly universal
↑ Serum aminotransferases and alkaline phosphatase
Portal hypertension and cirrhosis are rare
Severe cytopenias due to splenomegaly and marrow infiltration
Cholesterol gallstones may occur

Gold standard: glucocerebrosidase enzyme activity in leukocytes or nucleated cells
Genetic testing for GBA mutations provides prognostic insight
Liver biopsy: PAS-positive Gaucher cells with “crinkled paper” appearance

Comparison of Gaucher Disease Types
Feature	Type 1 (Nonneuronopathic)	Type 2 (Acute Neuronopathic)	Type 3 (Chronic Neuronopathic)
Onset	Childhood to adulthood	Within first 3 months of life	Variable; often in childhood
Neurological Involvement	Absent	Severe; seizures, eye movement abnormalities	Mild to moderate; progressive
Organomegaly	Massive hepatosplenomegaly	Severe hepatosplenomegaly	Present; variable severity
Bone Disease	Osteopenia, osteonecrosis	Rare	Common
Prognosis	Good with treatment; normal lifespan possible	Poor; death by age 2–4	Variable; slower progression
ERT Availability	Yes	No	Yes (for visceral symptoms)