Acid Sphingomyelinase Deficiency: Sharing Experience of Disease Monitoring and Severity in France

Abstract

Acid sphingomyelinase deficiency (ASMD) is a rare inherited lipid storage disorder caused by a deficiency in lysosomal enzyme acid sphingomyelinase which results in the accumulation of sphingomyelin, predominantly within cells of the reticuloendothelial system located in numerous organs, such as the liver, spleen, lungs, and central nervous system. Although all patients with ASMD share the same basic metabolic defect, a wide spectrum of clinical presentations and outcomes are observed, contributing to treatment challenges. While infantile neurovisceral ASMD (also known as Niemann–Pick disease type A) is rapidly progressive and fatal in early childhood, and the more slowly progressive chronic neurovisceral (type A/B) and chronic visceral (type B) forms have varying clinical phenotypes and life expectancy. The prognosis of visceral ASMD is mainly determined by the association of hepatosplenomegaly with secondary thrombocytopenia and lung disease. Early diagnosis and appropriate management are essential to reduce the risk of complications and mortality. The accessibility of the new enzyme replacement therapy olipudase alfa, a recombinant human ASM, has been expedited for clinical use based on positive clinical data in children and adult patients, such as improved respiratory status and reduced spleen volume. The aim of this article is to share the authors experience on monitoring ASMD patients and stratifying the severity of the disease to aid in care decisions.

Healthcare Service Use Patterns Among Patients with Acid Sphingomyelinase Deficiency Type B: A Retrospective US Claims Analysis

“…Additional assessments (echocardiogram, lung imaging, coronary artery status, and skeletal health assessment) should be conducted periodically (every 2–4 years). However, it is suggested that in the real-world setting, patients with ASMD type B are monitored and assessed less frequently [ 12 , 16 ]. In the primary analysis cohort of 47 patients, pulmonary function tests, lipid panels, and hepatic function panels contributed approximately 5% of overall service events, thereby demonstrating the need for better and more frequent clinical assessment for these patients.…”

“…At the time of the analysis, there were no approved disease-modifying therapies and therefore pharmacologic treatment for ASMD type B focused on supportive treatment and symptom management. Recommended therapies to control symptoms include lipid-lowering agents, prophylactic antibiotics, bronchodilators, non-selective beta-blockers, and vitamin D supplements to support bone function; bisphosphonates should not be used because they are inhibitors of acid sphingomyelinase [ 1 , 12 , 16 ]. Vaccination against pulmonary infections such as pneumococci, Haemophilus influenzae type B, meningococci, and influenza virus is also recommended [ 12 , 16 ].…”

“…Recommended therapies to control symptoms include lipid-lowering agents, prophylactic antibiotics, bronchodilators, non-selective beta-blockers, and vitamin D supplements to support bone function; bisphosphonates should not be used because they are inhibitors of acid sphingomyelinase [ 1 , 12 , 16 ]. Vaccination against pulmonary infections such as pneumococci, Haemophilus influenzae type B, meningococci, and influenza virus is also recommended [ 12 , 16 ]. Our findings reflect this guidance to a certain degree: the most widely used types of medication were antibiotics, lipid-lowering agents, and respiratory medications, while no prescriptions for bisphosphonates were made.…”

Consensus clinical management guidelines for acid sphingomyelinase deficiency (Niemann–Pick disease types A, B and A/B)

“…The guideline development group had extensive discussion about olipudase alfa use in patients with acute or rapidly progressive neurologic disease, as they were excluded from the ASCEND-Peds study (NCT02292654/Sanofi Genzyme) given the inability of the intravenously administered enzyme to cross the blood brain barrier or impact neurologic disease. However, early managed access programs allowed some patients with visceral and neurologic manifestations of ASMD access to olipudase alfa with a focus on ameliorating visceral signs and symptoms [ 130 , 131 ]. National patient organizations surveyed parents of children who received olipudase alfa for at least 12 months, including some patients with visceral and neurologic manifestations of ASMD.…”