Overview

• Most prevalent lysosomal storage disorder.
• Elevated incidence in Ashkenazi Jews (6% carrier frequency).
• Autosomal recessive inborn error of metabolism.
• Caused by mutations in the GBA1 gene, leading to deficient glucocerebrosidase activity.
• Characterized by toxic accumulation of glucocerebroside lipids in multiple organs.

Clinical Manifestations

1. Hepatosplenomegaly:
   • Enlarged liver and spleen.
2. Hematologic:
   • Pancytopenia (anemia, thrombocytopenia, leukopenia).
   • Risk of bleeding and infections.
3. Skeletal:
   • Osteoporosis, bone crises, avascular necrosis, pathological fractures.
   • Erlenmeyer flask deformity.
4. Metabolic:
   • Abnormal body weight, insulin resistance, lipid metabolism issues.
5. Neurological (types 2 and 3):
   • Seizures, intellectual disability, myoclonus, ocular apraxia.

Etiology

• Mutation in GBA1 gene → Deficient glucocerebrosidase → Lipid accumulation.
• Lysosomal storage disorder (like Tay-Sachs and Fabry disease).
• Variability in phenotype even among individuals with the same mutation.

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