FRCPath Haem Part 1 MCQs-Gen Haem 440

A 42-year-old man of Ashkenazi Jewish ancestry is referred to the haematology clinic for investigation of longstanding thrombocytopenia and splenomegaly.

Over the preceding five years, he has developed worsening fatigue, intermittent severe pain affecting both femora and hips, and progressive limitation in exercise tolerance. He reports that several episodes of bone pain were initially diagnosed as "sports injuries" despite occurring without significant trauma. He also describes easy bruising and occasional epistaxis.

On examination, he appears pale. The spleen is palpable 15 cm below the left costal margin and the liver is enlarged 4 cm below the right costal margin.

Investigations reveal:

• Hb 98 g/L

• WBC 4.1 × 10⁹/L

• Platelets 68 × 10⁹/L

• Ferritin 1,800 µg/L

• Fibrinogen 1.4 g/L (low)

• Serum protein electrophoresis demonstrates a small IgG paraprotein

• Skeletal radiographs show bilateral deformities of the distal femora

The referring physician concludes that the diagnosis has been established based on the marrow findings and asks whether treatment should be started immediately.

Which of the following is the SINGLE BEST next step?

A. Commence enzyme replacement therapy because Gaucher cells on bone marrow examination are diagnostic

B. Measure leukocyte acid glucocerebrosidase activity and perform GBA1 mutation analysis to confirm the diagnosis

C. Diagnose pseudo-Gaucher disease because a paraprotein is present and no further investigations are required

D. Perform splenectomy because splenomegaly is responsible for all clinical manifestations

E. Initiate substrate reduction therapy with eliglustat immediately and perform CYP2D6 genotyping later if symptoms improve