Exploring the boundaries of Niemann-Pick disease type A/B: a report of a case and review of literature.

backgroundAcid sphingomyelinase deficiency (ASMD), also known as Niemann-Pick disease types A and B, is a rare autosomal recessive lysosomal storage disorder caused by SMPD1 mutations. It is characterized by sphingomyelin accumulation and a broad clinical spectrum ranging from severe neurodegeneration in type A to a milder visceral phenotype in type B. Intermediate forms (type A/B) show overlapping features of both subtypes. CASE PRESENTATION: We report a 6-month-old boy with ASMD type A/B who first presented with meningoencephalitis and a single seizure most likely secondary to an intercurrent viral infection rather than a primary disease manifestation. Subsequent evaluation revealed multiple systemic red-flag features including marked hepatosplenomegaly, severe growth failure, a cherry-red spot, macroglossia, dysmorphic facial features, recurrent pneumonia, and bilateral sensorineural hearing loss. Laboratory investigations demonstrated elevated liver enzymes and cerebrospinal fluid abnormalities, while auditory brainstem response confirmed the hearing impairment. Enzyme assay confirmed reduced ASM activity, and targeted SMPD1 genetic sequencing identified a homozygous frameshift mutation classified as pathogenic according to ACMG criteria, establishing the diagnosis of an intermediate ASMD phenotype. 

conclusionThis case highlights the diagnostic challenges posed by ASMD type A/B, particularly when the initial presentation mimics an acute infection. The overlap of coincidental infectious illness with systemic red-flag features, the clinical variability of intermediate phenotypes, and the rarity of the disorder all contribute to delayed recognition. These factors underscore the importance of maintaining a high index of suspicion and pursuing early metabolic and genetic testing in atypical pediatric presentations.

trial registrationNot applicable.