Non-neuronopathic Gaucher disease due to saposin C deficiency

Clin Genet. 2007 Dec;72(6):538-42. doi: 10.1111/j.1399-0004.2007.00899.x. Epub 2007 Oct 7.


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.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Female
  • Gaucher Disease / diagnosis
  • Gaucher Disease / genetics*
  • Gaucher Disease / metabolism*
  • Humans
  • Male
  • Mutation, Missense
  • Phenotype
  • Saposins / deficiency*
  • Saposins / genetics*


  • PSAP protein, human
  • Saposins