Clinical scenario: Hyperactivity | Hearing impairment | Coarse facial feature| Pebbly papules
A 6-year-old boy is referred because of progressive behavioral problems, hearing impairment, recurrent otitis media, and declining school performance. His parents report that he has become increasingly hyperactive and aggressive over the past year. Examination reveals coarse facial features, macroglossia, hepatosplenomegaly, joint stiffness, and multiple pebbly ivory-colored papules over the scapular region and upper arms. Slit-lamp examination shows clear corneas.
Which of the following is the most likely diagnosis?
A. Hurler syndrome (MPS I)
B. Hunter syndrome (MPS II)
C. Morquio syndrome (MPS IV)
D. Sanfilippo syndrome (MPS III)
E. I-cell disease
Correct answer & Explanation:
Correct Answer: B. Hunter syndrome (MPS II)
Explanation:
Hunter syndrome (MPS II) results from iduronate-2-sulfatase deficiency and is inherited in an X-linked recessive pattern, making it the only mucopolysaccharidosis with this mode of inheritance.
This child has several classic features:
- Coarse facial features
- Hepatosplenomegaly
- Joint stiffness
- Hearing loss
- Progressive neurobehavioral decline
- Clear corneas (absence of corneal clouding)
- Pebbly skin lesions (“pebbling”), a highly characteristic but often overlooked feature of Hunter syndrome
These firm, ivory-colored papules and nodules over the scapulae, upper arms, chest, and thighs are considered a clinical clue that strongly favors Hunter syndrome over other mucopolysaccharidoses.
Why the Other Options Are Incorrect
A. Hurler syndrome (MPS I)
- Similar phenotype but corneal clouding is present.
- Autosomal recessive inheritance.
C. Morquio syndrome (MPS IV)
- Severe skeletal dysplasia with normal intelligence.
- Corneal clouding may occur, but pebbly skin lesions are absent.
D. Sanfilippo syndrome (MPS III)
- Marked neurodegeneration with relatively mild somatic features.
- Does not characteristically produce pebbly skin lesions.
E. I-cell disease
- Presents in infancy with severe developmental delay and skeletal abnormalities.
- Does not have the characteristic skin lesions or X-linked inheritance.
High-Yield Pearls
- Hunter syndrome = X-linked recessive MPS.
- No corneal clouding is the key feature distinguishing it from Hurler syndrome.
- Pebbly skin lesions over the scapulae and upper arms are highly characteristic and frequently tested in postgraduate examinations.
- Progressive hearing loss, airway disease, valvular heart disease, and neurocognitive decline are common.
- Diagnosis is confirmed by low iduronate-2-sulfatase activity.
- Enzyme replacement therapy (idursulfase) improves many systemic manifestations but has limited effect on central nervous system disease.
Exam Pearl
If an exam stem describes:
- Boy
- Coarse facies
- Hepatosplenomegaly
- Developmental regression
- Clear corneas
- Pebbly skin lesions
→ Think Hunter syndrome (MPS II) immediately.
