Improved sensitivity of an acid sphingomyelinase activity assay using a C6:0 sphingomyelin substrate

• Main Authors: Wei-Lien Chuang, Joshua Pacheco, Samantha Cooper, Jonathan S. Kingsbury, John Hinds, Pavlina Wolf, Petra Oliva, Joan Keutzer, Gerald F. Cox, Kate Zhang
• Format: Article
• Language: English
• Published: Elsevier 2015-06-01
• Series: Molecular Genetics and Metabolism Reports
• Subjects: Niemann–Pick disease type A/B; Acid sphingomyelinase activity; Screening; Natural substrate
• Online Access: http://www.sciencedirect.com/science/article/pii/S2214426915300057

Short-chain C6-sphingomyelin is an artificial substrate that was used in an acid sphingomyelinase activity assay for a pilot screening study of patients with Niemann–Pick disease types A and B. Using previously published multiplex and single assay conditions, normal acid sphingomyelinase activity levels (i.e. false negative results) were observed in two sisters with Niemann–Pick B who were compound heterozygotes for two missense mutations, p.C92W and p.P184L, in the SMPD1 gene. Increasing the sodium taurocholate detergent concentration in the assay buffer lowered the activity levels of these two patients into the range observed with other patients with clear separation from normal controls.