ASMD (acid sphingomyelinase deficiency), formerly Morbus Niemann-Pick type A/B: four adult cases with idiopathic hepatosplenomegaly and first results from enzyme replacement therapy (ERT) with olipudase alfa

Indroduction: Acid sphingomyelinase deficiency (ASMD) is an ultrarare lysosomal storage disorder with hepatosplenomegaly (HSM), interstitial lung disease (ILD) and dyslipidemia, caused by an autosomal-recessively inherited deficiency of acid sphingomyelinase (ASM) activity. Enzyme replacement therapy (ERT) with recombinant olipudase alfa is available since 2022.

Methods: Three-center retrospective study of NP-B patients between 2014-2024.

Results: Four patients were diagnosed enzymatically/genetically with ASMD. Patient#1, female, year of birth(YOB) 1962, posttraumatic splenectomy, had ILD in HR-CT and a HDL-Cholesterol concentration of 15mg/dl. Chitotriosidase activity(CTA) and lysosphingomyelin(Lyso-SPM) were massively elevated. CO diffusion lung capacity(DLCO) was 26% of normal. Pat.#2, male, YOB 1999, had hepatosplenomegaly, elevated CTA and lyso-SPM, low HDL-C and DLCO of 49%. Cognitive deficits, mild ataxia and microcephalus were found. Pat.#3, YOB1992, had hepatosplenomegaly and exertional dyspnea. CTA and lyso-SPM were elevated, HDL-C 21 was mg/dl. DLCO was 49%. Pat.#4, female, DOB2011, showed growth retardation, cognitive deficits, severe hepatosplenomegaly with liver cirrhosis, interstitial lung disease and dyslipidemia. Patients #1 and #3 were classified as type B ASMD, patients #2 and #4 as type A/B because of significant neurological findings. ERT was initiated. In Pat.#1 one year of ERT Tx led to an increase of DLCO from 26 to 53%, Lyso-SM normalized. In Pat.#2 and #3 spleen sizes decreased significantly, in both pts. CTA and lyso-SM improved, and DLCO increased. Pat. #4 is currently LTFU.

Conclusion: Olipudase alfa Tx seems to be safe and efficient with decreased biomarkers and improvement of visceral and lung manifestations in patients with ASMD type B and A/B.

Publication History

Article published online:
20 January 2025