A 4-year-old boy presents with progressive developmental delay, coarse facial features, hepatosplenomegaly, and characteristic ivory-colored skin papules over the scapulae. Audiometry reveals the pattern marked **B** in the diagram. Which of the following best explains the hearing loss pattern observed in this patient?
A. Deficiency of arylsulfatase B resulting in pure sensorineural hearing loss without middle ear involvement
B. Deficiency of iduronate-2-sulfatase leading to accumulation of dermatan and heparan sulfate in the middle ear and cochlea
C. Deficiency of galactocerebrosidase causing progressive high-frequency hearing loss with normal middle ear function
D. Deficiency of alpha-L-iduronidase causing corneal clouding and conductive hearing loss only
Explanation
Why option 1 is right
The clinical presentation—coarse facies, hepatosplenomegaly, characteristic pebbly ivory-colored skin papules over the scapulae, and progressive developmental delay—is pathognomonic for Hunter syndrome (MPS II). The pattern marked B (bilateral mixed conductive-sensorineural loss) is the characteristic hearing loss in Hunter syndrome. This mixed pattern results from two mechanisms: (1) conductive loss from chronic otitis media with effusion, eustachian tube dysfunction, and glycosaminoglycan (GAG) deposition in the ossicles; and (2) progressive sensorineural loss from cochlear involvement. Both components arise from lysosomal accumulation of dermatan sulfate and heparan sulfate due to iduronate-2-sulfatase (IDS) deficiency. The enzyme defect is encoded on chromosome Xq28, making this an X-linked recessive disorder affecting males. (Nelson Pediatrics 22e; Harrison 21e Ch 433)
Why each distractor is wrong
Option 2: Alpha-L-iduronidase deficiency causes Hurler syndrome (MPS I), which presents with corneal clouding—a KEY DISTINGUISHING FEATURE absent in Hunter syndrome. Hurler also typically presents earlier with more severe systemic disease and does not characteristically produce the pebbly ivory-colored papules seen here.
Option 3: Arylsulfatase B deficiency causes Maroteaux-Lamy syndrome (MPS VI), which presents with pure conductive or sensorineural hearing loss patterns, not the characteristic mixed pattern. MPS VI lacks the cognitive decline and behavioral changes seen in this patient's neuronopathic form.
Option 4: Galactocerebrosidase deficiency causes Krabbe disease (globoid cell leukodystrophy), a different lysosomal storage disorder characterized by high-frequency sensorineural hearing loss without the somatic features (coarse facies, hepatosplenomegaly, characteristic skin papules) or the mixed hearing loss pattern seen in Hunter syndrome.
High-YieldNEET PG
Hunter syndrome (MPS II) = X-linked IDS deficiency → mixed hearing loss (conductive from otitis media/ossicular GAG deposition + sensorineural from cochlear involvement) + clear corneas (unlike Hurler) + pebbly ivory papules over scapulae.
Nelson Pediatrics 22e; Harrison 21e Ch 433
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