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

Why It Matters

Early identification of atypical ASMD presentations enables timely supportive care, genetic counseling, and specialist referral, reducing morbidity in affected infants.

Key Takeaways

• Infantile ASMD can present with GI, respiratory symptoms.
• Hepatosplenomegaly and feeding intolerance prompted lysosomal disorder suspicion.
• SMPD1 splice‑site mutation confirmed Niemann‑Pick type A diagnosis.
• Early recognition prevents diagnostic delays in low‑resource settings.
• Multidisciplinary care essential for supportive management.

Pulse Analysis

Acid sphingomyelinase deficiency (ASMD) is a rare autosomal‑recessive lysosomal storage disorder that encompasses Niemann‑Pick disease types A and B. The infantile form, type A, classically manifests with rapid neuro‑visceral decline, including severe hypotonia, progressive hepatosplenomegaly, and early death. Because the enzymatic defect leads to sphingomyelin accumulation in multiple organs, symptoms can be heterogeneous, yet most clinicians first encounter neurological deterioration. Consequently, early‑stage disease often masquerades as more common pediatric ailments, creating a diagnostic blind spot that delays definitive treatment.

The Palestinian case illustrates how ASMD can initially masquerade as gastrointestinal and respiratory disease. The infant’s persistent vomiting, feeding intolerance, and recurrent right‑upper‑lobe pneumonia were initially managed as isolated infections and gastro‑esophageal reflux, while hepatosplenomegaly was attributed to infectious hepatitis. Only after standard therapies failed did the care team broaden the differential to include lysosomal storage disorders, prompting targeted molecular analysis. Identification of a homozygous c.1340+2T>C splice‑site mutation in SMPD1 confirmed type A disease, highlighting the decisive role of genetic testing in ambiguous pediatric presentations.

For health systems in low‑resource regions, this report underscores the value of clinical vigilance and access to affordable genetic diagnostics. Early recognition of atypical ASMD presentations can trigger multidisciplinary interventions—nutritional support, respiratory physiotherapy, and family counseling—that improve quality of life while awaiting disease‑modifying therapies under development. Moreover, documenting such cases builds a regional epidemiological database, informing newborn screening strategies and guiding policy decisions. As enzyme replacement and gene‑therapy pipelines advance, timely diagnosis will become increasingly critical to maximize therapeutic benefit.