|Name||Combined SAP deficiency;
|Description||Combined SAP deficiency is a fatal infantile lysosomal storage disorder with hepatosplenomegaly and severe neurological disease. It is caused by mutations in the PSAP gene leading to absence or non-functionality of the prosaposin protein. Mammalian prosaposin encodes in tandem four small acidic activator proteins (saposins) with specificities for glycosphingolipids hydrolases.|
|Category||Inherited metabolic disease; Lysosomal storage disease|
|Gene||PSAP [HSA:5660] [KO:K12382]|
|Comment||Defects in PSAP saposin-B region are the cause of metachromatic leukodystrophy [DS:H00127]. Defects in PSAP saposin-C region are the cause of atypical Gaucher disease [DS:H00126]. Defects in PSAP saposin-A region are the cause of atypical Krabbe disease [DS:H00135].|
|Other DBs||ICD-10: E75.2
Schnabel D, Schroder M, Furst W, Klein A, Hurwitz R, Zenk T, Weber J, Harzer K, Paton BC, Poulos A, et al.
Simultaneous deficiency of sphingolipid activator proteins 1 and 2 is caused by a mutation in the initiation codon of their common gene.
J Biol Chem 267:3312-5 (1992)
Hulkova H, Cervenkova M, Ledvinova J, Tochackova M, Hrebicek M, Poupetova H, Befekadu A, Berna L, Paton BC, Harzer K, Boor A, Smid F, Elleder M
A novel mutation in the coding region of the prosaposin gene leads to a complete deficiency of prosaposin and saposins, and is associated with a complex sphingolipidosis dominated by lactosylceramide accumulation.
Hum Mol Genet 10:927-40 (2001)
Sun Y, Witte DP, Zamzow M, Ran H, Quinn B, Matsuda J, Grabowski GA
Combined saposin C and D deficiencies in mice lead to a neuronopathic phenotype, glucosylceramide and alpha-hydroxy ceramide accumulation, and altered prosaposin trafficking.
Hum Mol Genet 16:957-71 (2007)