2026/06/28 by Maria Cristina Robin, Consuelo Durand, Guillermo Guelbert +8 · 1 voice
Medicine · Biochemistry, Genetics and Molecular Biology · #Lysosomal Storage Disorders Research #Autoimmune and Inflammatory Disorders Research #Sphingolipid Metabolism and Signaling
paper · doi:10.1002/jmd2.70104
openalex publication_date 2026/06/28 · openalex created_date 2026/06/30 · openalex updated_date 2026/08/01
ABSTRACT Acid sphingomyelinase deficiency (ASMD), historically known as Niemann‐Pick disease, is a rare and potentially fatal lysosomal storage disease caused by pathogenic variants in the sphingomyelin phosphodiesterase 1 ( SMPD1 ) gene, which encodes acid sphingomyelinase (ASM). Deficient ASM activity results in dysregulation of cellular membrane homeostasis and accumulation of sphingomyelin in multiple organs. ASMD spans a broad clinical spectrum, with symptoms varying at presentation depending on age at onset and degree and type of organ/systemic involvement. To describe the diagnostic experience and clinical manifestations of ASMD in Argentina, a national retrospective case series was conducted across seven centers in patients diagnosed between 1988 and 2022. Diagnosis was confirmed by reduced ASM activity, with SMPD1 sequencing performed when possible. Nineteen patients (8 females/11 males; 0–76 years) were identified: Type A (4, 21%), Type B (12, 63%), Type A/B (2, 11%), and one unknown. Average age at symptom onset was 3.9 years, and average age at diagnosis was 11.4 years, corresponding to a diagnostic delay of 7.5 years. All patients presented with hepatosplenomegaly. Anemia (79%), pulmonary involvement (79%), thrombocytopenia (79%), and osteopenia (56%) were also reported in a majority of patients. Two patients were initially misdiagnosed with Gaucher disease. This series highlights the variety of clinical presentations and substantial diagnostic delays associated with ASMD in Argentina. Increasing awareness across specialties is essential to improve disease recognition, reduce time to diagnosis, and prevent misdiagnosis.