H Salman, H Özbaş, RO Yüceer, M Akçam

Abstract

Prosaposin deficiency is a rapidly progressive fatal neurovisceral lysosomal storage disorder (LSD) caused by pathogenic variation in the PSAP gene. The phenotype overlaps with LSDs and the short lifespan of patients has led to misdiagnosis of these complex and rare diseases. A 2-month-old girl presented with encephalopathy, resistant tonic-clonic seizures, giant hepatosplenomegaly, hypotonia, and delay in head control with lack of sucking reflex. Due to persistent respiratory distress and resistant seizures, the child succumbed in the fourth month of her life. Although clinical findings suggest Gaucher disease, the diagnosis was rejected because of normal β-glucosidase activity. Whole exome sequencing identified a previously unidentified homozygous, frameshift, clearly pathogenic variant of p.Arg186Profs*9 (c.551dupG) in the PSAP gene. This frameshift variation has been classified as "likely pathogenic," according to the ACMG Guidelines. As a result of homozygous variation in PSAP gene our case was accepted as combined prosaposin deficiency with early infantile onset and severe neurological involvement. Detected frameshift variation that leading protein length changes has not been previously reported.