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

TL;DR

This study examines genetic variants and treatment outcomes in Taiwanese patients with acid sphingomyelinase deficiency, highlighting the effectiveness of olipudase alfa, especially when treatment starts early.

Contribution

The study identifies specific SMPD1 variants in Taiwanese ASMD patients and demonstrates clinical benefits of olipudase alfa treatment initiated in early childhood.

Findings

The SMPD1 c.1497_1498inv variant was found in 62.5% of chronic neurovisceral ASMD alleles.

Olipudase alfa treatment improved pulmonary function and other clinical features in patients, especially when started early.

Newborn screening using the NeoLSD MS/MS kit helped detect ASMD cases with partial presentations.

Abstract

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.

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.

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.

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.

In Taiwan, the SMPD1 c.1497_1498inv variant was common in chronic neurovisceral acid sphingomyelinase deficiency (ASMD), while c.995C > G was more frequently observed in chronic visceral ASMD. Four patients treated with olipudase alfa showed clinical improvements, particularly when treatment was started in early childhood.

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