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.
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.
Spiegel
Ronen
R
Department of Pediatrics, HaEmek Medical Center, Afula, Israel.
Bach
Gideon
G
Sury
Vivi
V
Mengistu
Getu
G
Meidan
Bela
B
Shalev
Stavit
S
Shneor
Yona
Y
Mandel
Hanna
H
Zeigler
Marsha
M
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*
D017931:DNA Primers; D049231:Saposins; D005698:Galactosylceramidase