title: Improved sensitivity of an acid sphingomyelinase activity assay using a C6:0 sphingomyelin substrate.
abstract: 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.
authors.affiliation: Genzyme Corporation, a Sanofi Company, One Mountain Road, Framingham, MA 01701-9322, USA.
authors.forename: Wei-Lien
authors.initials: WL
authors.lastname: Chuang
authors.affiliation: Genzyme Corporation, a Sanofi Company, One Mountain Road, Framingham, MA 01701-9322, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Pacheco
authors.affiliation: Genzyme Corporation, a Sanofi Company, One Mountain Road, Framingham, MA 01701-9322, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Cooper
authors.affiliation: Genzyme Corporation, a Sanofi Company, One Mountain Road, Framingham, MA 01701-9322, USA.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Kingsbury
authors.affiliation: Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA.
authors.forename: John
authors.initials: J
authors.lastname: Hinds
authors.affiliation: Genzyme Corporation, a Sanofi Company, One Mountain Road, Framingham, MA 01701-9322, USA.
authors.forename: Pavlina
authors.initials: P
authors.lastname: Wolf
authors.affiliation: Genzyme Corporation, a Sanofi Company, One Mountain Road, Framingham, MA 01701-9322, USA.
authors.forename: Petra
authors.initials: P
authors.lastname: Oliva
authors.affiliation: Genzyme Corporation, a Sanofi Company, One Mountain Road, Framingham, MA 01701-9322, USA.
authors.forename: Joan
authors.initials: J
authors.lastname: Keutzer
authors.affiliation: Genzyme Corporation, a Sanofi Company, One Mountain Road, Framingham, MA 01701-9322, USA; Division of Genetics, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Cox
authors.affiliation: Genzyme Corporation, a Sanofi Company, One Mountain Road, Framingham, MA 01701-9322, USA.
authors.forename: Kate
authors.initials: K
authors.lastname: Zhang
keywords: Acid sphingomyelinase activity; Natural substrate; Niemann–Pick disease type A/B; Screening