title: A mutation in the saposin A coding region of the prosaposin gene in an infant presenting as Krabbe disease: first report of saposin A deficiency in humans.
abstract: A six-month-old infant girl presenting with progressive encephalopathy and abnormal myelination in the cerebral white matter was originally diagnosed as suffering from Krabbe disease. The diagnosis was based on a deficiency of galactocerebrosidase activity found in leukocytes isolated from whole blood. When cultured skin fibroblasts did not show a similar enzyme deficiency and sulphatide (stearoyl-1-14C) uptake indicated an abnormal storage of galactosylceramide, a deficiency of an activator was implied. A three base pair deletion was found in the saposin A coding sequence of the prosaposin gene leading to the deletion of a conserved valine at amino acid number 11 of the saposin A protein. This deletion in saposin A is proposed as the cause for the abnormal galactosylceramide metabolism in this infant. This is the first report of a saposin A mutation in humans leading to pathological consequences.
authors.affiliation: Department of Pediatrics, HaEmek Medical Center, Afula, Israel.
authors.forename: Ronen
authors.initials: R
authors.lastname: Spiegel
authors.forename: Gideon
authors.initials: G
authors.lastname: Bach
authors.forename: Vivi
authors.initials: V
authors.lastname: Sury
authors.forename: Getu
authors.initials: G
authors.lastname: Mengistu
authors.forename: Bela
authors.initials: B
authors.lastname: Meidan
authors.forename: Stavit
authors.initials: S
authors.lastname: Shalev
authors.forename: Yona
authors.initials: Y
authors.lastname: Shneor
authors.forename: Hanna
authors.initials: H
authors.lastname: Mandel
authors.forename: Marsha
authors.initials: M
authors.lastname: Zeigler
mesh_terms: D000649:Amniocentesis; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D005698:Galactosylceramidase / Q000378:metabolism; D006801:Humans; D007223:Infant; D007965:Leukodystrophy, Globoid Cell / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D009154:Mutation; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D049231:Saposins / Q000235:genetics*
chemical_list: D017931:DNA Primers; D049231:Saposins; D005698:Galactosylceramidase