RESUMO
Gaucher disease is caused by glucocerebroside accumulation in different tissues due to beta-glucocerebrosidase enzyme deficiency. Genetic defects in proteins involved in beta-glucocerebrosidase processing and activation may indirectly lead to Gaucher-like phenotypes in affected individuals. Saposin C, derived from the prosaposin precursor, is a crucial activator for beta-glucocerebrosidase, and its deficiency has been linked to Gaucher-like phenotypes in several clinical reports. Here, we report two Emirati families with Gaucher-like disorder due to Saposin C deficiency. Affected patients from both families carry the homozygous state of the novel c.1005 + 1G > A splice site (first to be reported) variant in the PSAP gene. Molecular analysis showed that the underlying variant is predicted to result in the retention of intron 9-10 and the formation of a premature stop codon leading to the complete loss of Saposin C. Clinical examination of the affected patients showed a wide heterogeneity in the patients' age of onset and symptoms ranging from Gaucher-like type 3 phenotype with severe refractory myoclonic epilepsy to Gaucher-like type 1 phenotype with growth retardation and hepatosplenomegaly. Collectively, the available clinical and molecular data confirms the pathogenicity of the reported PSAP splice site variant. The reported clinical cases expand the genetic and clinical spectrum of Saposin C deficiency.
