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

## TL;DR

A 6-month-old boy with a rare genetic disorder called Niemann-Pick disease type A/B is reported, highlighting the challenges in diagnosing this condition due to its varied and complex symptoms.

## Contribution

The paper presents a rare case of ASMD type A/B with an unusual initial presentation, emphasizing diagnostic challenges and the need for early genetic testing.

## Key findings

- The patient exhibited systemic red-flag features including hepatosplenomegaly, growth failure, and neurological signs.
- A homozygous frameshift mutation in SMPD1 was identified, confirming the intermediate ASMD phenotype.
- The case underscores the importance of metabolic and genetic testing in atypical pediatric presentations.

## Abstract

Acid 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.

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.

This 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.

Not applicable.

The online version contains supplementary material available at 10.1186/s40348-025-00206-z.