Clinical Scenario:
A 2-year-old boy is brought with progressive developmental regression that began at 15 months of age. He initially developed normally but subsequently lost acquired motor and language skills. Examination reveals generalized hypotonia, hepatosplenomegaly, and a cherry-red spot on fundoscopy. He also has an exaggerated startle response to sudden sounds. Which of the following is the most likely diagnosis?
A. Tay-Sachs disease
B. Niemann-Pick disease type A
C. Krabbe disease
D. Metachromatic leukodystrophy
E. Rett syndrome
Correct answer & Explanation:
Answer: B. Niemann-Pick disease type A
Explanation
Niemann-Pick disease type A is caused by acid sphingomyelinase deficiency, resulting in accumulation of sphingomyelin within macrophages and tissues. It typically presents in infancy with progressive neurodegeneration, hypotonia, hepatosplenomegaly, and a cherry-red spot on the macula.
The key distinction from Tay-Sachs disease is visceral involvement. Tay-Sachs classically causes progressive neurodegeneration, an exaggerated startle response, and a cherry-red macular spot, but hepatosplenomegaly is absent.
Krabbe disease usually presents with irritability, developmental regression, spasticity, and peripheral neuropathy, while metachromatic leukodystrophy typically presents later with regression, ataxia, and peripheral neuropathy. Rett syndrome predominantly affects girls and is characterized by developmental regression with loss of purposeful hand skills and stereotypic hand movements.
