A 3-year-old boy has global developmental delay, recurrent pulmonary infections, splenomegaly, and a bone marrow biopsy showing large macrophages with wrinkled tissue-paper cytoplasm (Gaucher cells). The deficient enzyme is glucocerebrosidase (beta-glucosidase). Enzyme replacement therapy (ERT) is indicated. Which clinical feature distinguishes Type 2 (acute neuronopathic) from Type 1 (non-neuronopathic) Gaucher disease and prevents ERT from being curative in Type 2?

• A Presence of Gaucher cells in bone marrow
• B Severity of splenomegaly and bone marrow infiltration
• C Earlier age of onset with more severe cytopenia
• D Blood-brain barrier limits ERT access; progressive neurodegeneration continues despite systemic ERT ✓

Explanation

Type 1 Gaucher disease (non-neuronopathic) is managed effectively with IV enzyme replacement therapy (imiglucerase, velaglucerase, taliglucerase) which reverses organomegaly, cytopenias, and bone disease. In Type 2 (acute infantile neuronopathic) and Type 3 (subacute neuronopathic) Gaucher disease, the blood-brain barrier prevents IV ERT from reaching CNS neurons, so neurodegeneration proceeds unabated despite excellent systemic control. This is why ERT is not curative in neuronopathic types. Gaucher cells in bone marrow are present in all types. The severity of splenomegaly and age at onset do not differentiate neurological from non-neurological types in terms of treatment response.

Reference: Ghai Essential Pediatrics, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.