Mutations in the PSAP gene have been associated with prosaposin deficiency, Krabbe disease, metachromatic leukodystrophy and Gaucher disease. There have been only a few reports of patients with prosaposin deficiency all of whom were described as having a severe neurovisceral storage disease that was evident at birth with a rapidly fatal course. Hypotonia, hepatosplenomegaly, myoclonic jerks, abnormal ocular movements, dystonia and seizures were also described. At this time, only a single patient has been described with Krabbe disease due to saposin A deficiency. This patient had dysmyelination of the cerebral white matter with a very rapid neurological deterioration that ended in death at eight months.
Most patients with metachromatic leukodystrophy due to saposin B deficiency have presented with the late infantile form in which symptoms appear between the ages of 1 to 2 years with neuroregression, walking difficulties, dysarthria and lower limb spacticity. Patients with the juvenile-onset and adult-onset forms have also been described. In Saudi Arabia metachromatic leukodystrophy due to saposin B deficiency appears to be more common than the classic arylsulfatase A-deficient metachromatic leukodystrophy.
The majority of patients with Gaucher disease due to saposin C deficiency have most often been described as having type 3 (subacute or chronic neuronopathic) Gaucher disease that is characterized by severe systemic involvement and supranuclear saccadic horizontal gaze palsy, with our without developmental delay, hearing impairment and other brainstem deficits, or a relatively mild systemic disease but with progressive myoclonic encephalopathy, seizures, dementia and death. However, patients with saposin C deficiency who have the more common type 1 Gaucher disease presentation have also been reported.