Mucopolysaccharidoses and oligosaccharidoses — formative SAQs

Question 1 (10 marks)

A three-year-old boy who appeared normal at birth is referred for progressive coarsening of the facial features, persistent umbilical hernia, snoring, and slowing of speech. Examination reveals macroglossia, hepatosplenomegaly with the liver edge 4 cm below the costal margin, claw-hand deformity, and a thoracolumbar gibbus. A skeletal survey shows dysostosis multiplex. The cornea is clear and he is a boy. [1] [2]

(a) Give the most likely disorder family and the single most discriminating bedside feature pointing to the subtype, justifying why the clear cornea matters. (3 marks) [1]

(b) Outline the stepwise confirmatory investigation strategy, naming the first-line screening test, the confirmatory enzyme test, and the molecular test, and explain how the urinary glycosaminoglycan pattern is used. (4 marks) [1] [2]

(c) Explain why the treatment modality depends on whether the central nervous system is involved, naming the two principal disease-modifying options and the constraint on each. (3 marks) [2] [3]

Question 2 (10 marks)

A six-month-old who had been developing normally now has a coarse face, striking gingival hyperplasia, restricted joints, and cardiomegaly. Laboratory testing reveals that several plasma lysosomal enzyme activities are markedly elevated rather than deficient, while cultured fibroblast enzyme activities are low. [2]

(a) Give the unifying diagnosis and explain the paradox of the elevated plasma enzymes in one sentence. (3 marks) [2]

(b) Contrast this disorder's prognosis and management with that of severe Hurler syndrome (MPS I), naming the disease-modifying option that has transformed Hurler outcome and the timing constraint that governs it. (4 marks) [2] [4]

(c) A four-year-old with severe hyperactivity, aggression, sleep reversal, and only mild coarsening is referred. Name the likely subtype and explain why the parents' presenting complaint is behavioural rather than somatic. (3 marks) [1] [2]