title: Non-neuronopathic Gaucher disease due to saposin C deficiency.
abstract: Gaucher disease is generally caused by a deficiency of the lysosomal enzyme glucocerebrosidase. The degradation of glycosphingolipids requires also the participation of sphingolipid activator proteins. The prosaposin PSAP gene codes for a single protein which undergoes post-translational cleavage to yield four proteins named saposins A, B, C and D. Saposin (SAP-) C is required for glucosylceramide degradation, and its deficiency results in a variant form of Gaucher disease. In this report, we present clinical, biochemical, and molecular findings in a 36-year-old man and his 30-year-old sister with non-neuronopathic Gaucher disease due to SAP-C deficiency. Very high levels of chitotriosidase activity, chemokine CCL18, and increased concentration of glucosylceramide in plasma and normal beta-glucosidase activity in skin fibroblasts were observed in the patients. A molecular genetics study of the PSAP gene enabled the identification of one missense mutation, p.L349P, located in the SAP-C domain and another mutation, p.M1L, located in the initiation codon of the prosaposin precursor protein. The presented findings describe the first cases where the non-neuronopathic Gaucher disease has been definitely demonstrated to be a consequence of SAP-C deficiency. Three previously described cases in the literature displayed a Gaucher type 3 phenotype.
authors.affiliation: Department of Metabolic Diseases, Endocrinology, and Diabetology, The Children's Memorial Health Institute, Warsaw, Poland. a.tylki@czd.pl
authors.forename: A
authors.initials: A
authors.lastname: Tylki-Szymańska
authors.forename: B
authors.initials: B
authors.lastname: Czartoryska
authors.forename: M-T
authors.initials: MT
authors.lastname: Vanier
authors.forename: B J M H
authors.initials: BJ
authors.lastname: Poorthuis
authors.forename: J A E
authors.initials: JA
authors.lastname: Groener
authors.forename: A
authors.initials: A
authors.lastname: Ługowska
authors.forename: G
authors.initials: G
authors.lastname: Millat
authors.forename: A M
authors.initials: AM
authors.lastname: Vaccaro
authors.forename: E
authors.initials: E
authors.lastname: Jurkiewicz
mesh_terms: D000328:Adult; D005260:Female; D005776:Gaucher Disease / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010641:Phenotype; D049231:Saposins / Q000172:deficiency* / Q000235:genetics*
chemical_list: C483345:PSAP protein, human; D049231:Saposins