Clinical scenario: Breathlessness | Coarse features | Macroglossia | Hepatosplenomegaly
A 4-year-old boy is brought with progressive breathlessness on exertion, easy fatigability, and recurrent chest infections. Examination reveals coarse facial features, corneal clouding, macroglossia, short stature, hepatosplenomegaly, joint stiffness, and claw hands. Cardiac auscultation detects a grade 3/6 pansystolic murmur at the apex. Echocardiography shows thickened mitral and aortic valves with severe mitral regurgitation and left ventricular hypertrophy.
Which of the following is the most likely diagnosis?
A. Hunter syndrome (MPS II)
B. Hurler syndrome (MPS I)
C. Morquio syndrome (MPS IV)
D. Pompe disease
E. GM1 gangliosidosis
Correct answer & Explanation:
Correct Answer: B. Hurler syndrome (MPS I)
Explanation
Hurler syndrome is caused by α-L-iduronidase deficiency, leading to accumulation of dermatan sulfate and heparan sulfate. The disease typically presents in early childhood with:
- Coarse facial features
- Corneal clouding
- Hepatosplenomegaly
- Developmental delay
- Joint stiffness and dysostosis multiplex
- Recurrent respiratory infections
- Progressive cardiac disease, particularly:
- Mitral and aortic valve thickening
- Mitral regurgitation and/or aortic regurgitation
- Left ventricular hypertrophy
- Coronary artery involvement
Cardiac disease is a major cause of morbidity and mortality in untreated patients.
Why the Other Options Are Incorrect
- A. Hunter syndrome (MPS II): Similar clinical features, but corneal clouding is absent.
- C. Morquio syndrome (MPS IV): Severe skeletal abnormalities with normal intelligence and minimal cardiac involvement compared with Hurler syndrome.
- D. Pompe disease: Causes hypertrophic cardiomyopathy and hypotonia but lacks corneal clouding, coarse facies, and valvular disease typical of MPS I.
- E. GM1 gangliosidosis: May have neurodegeneration and dysmorphism but does not characteristically cause the combination of corneal clouding and progressive valvular heart disease.
High-Yield Pearls
- Hurler = Corneal clouding + coarse facies + hepatosplenomegaly + valvular heart disease.
- Hunter = Same phenotype but no corneal clouding.
- The most common cardiac lesion in Hurler syndrome is mitral valve thickening/regurgitation, followed by aortic valve involvement.
- Early hematopoietic stem cell transplantation (before 2 years of age) offers the best chance of preserving neurocognitive function, while laronidase enzyme replacement therapy improves many systemic manifestations but has limited penetration into the central nervous system.
