Infantile Acid Sphingomyelinase Deficiency Presenting With Severe Gastrointestinal and Recurrent Respiratory Symptoms: A Diagnostic Challenge Case Report in Palestine

Abstract Background: Acid sphingomyelinase deficiency (ASMD), encompassing Niemann–Pick disease types A and B, is a rare autosomal recessive lysosomal storage disorder. Infantile ASMD (type A) typically presents with progressive neurovisceral involvement. However, early manifestations may be nonspecific, leading to delayed diagnosis. We report an unusual presentation of infantile ASMD characterized by prominent gastrointestinal and respiratory symptoms, highlighting diagnostic challenges in pediatric practice. Case presentation: An 8-month-old male infant presented with progressive abdominal distension, persistent projectile vomiting, feeding intolerance, failure to thrive, recurrent respiratory infections, and hypotonia since early infancy. He was repeatedly treated for common pediatric conditions without sustained improvement. Imaging demonstrated marked hepatosplenomegaly and recurrent right upper-lobe pneumonia. Laboratory evaluation revealed markedly elevated liver enzymes with preserved synthetic function. Due to the combination of hepatosplenomegaly, hypotonia, and chronic feeding difficulties, a lysosomal storage disorder was suspected. Molecular genetic testing identified a homozygous pathogenic splice-site variant in the SMPD1 gene (c.1340+2T>C), confirming the diagnosis of infantile acid sphingomyelinase deficiency (Niemann–Pick disease type A). Supportive multidisciplinary management was initiated, including nutritional and respiratory care. Conclusions: This case illustrates an atypical early presentation of infantile ASMD with predominant gastrointestinal and respiratory manifestations preceding classical features. Awareness of such presentations is essential to avoid diagnostic delay, particularly in resource-limited settings. Early recognition facilitates appropriate supportive care, genetic counseling, and timely referral to specialized centers.