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: Ronen Spiegel, Gideon Bach, Vivi Sury, Getu Mengistu, Bela Meidan, Stavit Shalev, Yona Shneor, Hanna Mandel, Marsha Zeigler
• Journal: Molecular genetics and metabolism (Mol Genet Metab) Vol. 84 Issue 2 Pg. 160-6 (Feb 2005) ISSN: 1096-7192 [Print] United States
• PMID: 15773042 (Publication Type: Case Reports, Journal Article)

Chemical References

• DNA Primers
• Saposins
• Galactosylceramidase

Topics

• Amniocentesis
• Base Sequence
• DNA Primers
• Female
• Galactosylceramidase (metabolism)
• Humans
• Infant
• Leukodystrophy, Globoid Cell (enzymology, genetics, pathology)
• Magnetic Resonance Imaging
• Mutation
• Polymerase Chain Reaction
• Pregnancy
• Saposins (genetics)