Pathogenic Variants and Olipudase Alfa Treatment of Patients With Acid Sphingomyelinase Deficiency in Taiwan.

BACKGROUND: Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal disorder with diverse clinical presentations and often delayed diagnosis. This study investigates the clinical features, genetic variants, and treatment outcomes in Taiwanese patients. METHODS: We retrospectively reviewed nine ASMD cases in Taiwan, including genetic data and responses to olipudase alfa. Newborn screening data using the NeoLSD MS/MS kit for dried blood spot enzyme activity, followed by lyso-sphingomyelin and molecular testing, were also analysed. RESULTS: The SMPD1 c.1497_1498inv variant was found in 62.5% of alleles among chronic neurovisceral ASMD cases, while c.995C > G appeared in 37.5% of chronic visceral ASMD cases and was also frequent in partial ASMD from newborn screening. Four patients received olipudase alfa; Patient 1, treated for 3 years starting at age 41, showed improved pulmonary function despite persistent thrombocytopenia and splenomegaly. Patients 2, 6, and 7, treated from early childhood, exhibited marked improvements in hepatosplenomegaly, interstitial lung disease, and growth within 1 year of therapy. CONCLUSION: This study highlights distinct genotype-phenotype correlations in ASMD and supports the clinical benefits of olipudase alfa. Increased awareness and early diagnosis, potentially through newborn screening, are essential for optimizing outcomes in ASMD.