Combined saposin deficiency
Combined Saposin Defiency is a very rare metabolic and genetic disorder that is caused by the mutation in a gene PSAP. This disease belongs to Lysosomal Storage Diseases. Because of complete saposin deficiency, it can cause clinical features of 4 diseases to be apparent.
Cause
PSAPD is caused by mutations in a PSAP gene, which is located on the long arm of chromosome 10.PSAPD is inherited in a Autosomal Recessive fashion.
Symptoms
Symptoms usually start in infancy or in neonatal age. The signs of this disease are respiratory failure, hepatosplenomegaly, poor feeding, myoclonus, hyperkinetic movements, clonic seizures, leukodystrophy, hypotonia, abnormality of eye movement and a neuronal loss.Optic atrophy was only reported in 1 patient
Pathophysiology
It’s known that Prosaposin is a precursor of a Saposin A,B,C,D. Saposin A is needed to activate galactocerbroside hydrolysis, Saposin B for sulphatide hydrolysis activation, Saposin C for glucocerebroside hydrolysis, Saposin D might activate hydrolysis of ceramide.According to one study, Prosaposin might be involved in neuron and glial protection by extracellular secretion and activation of some G protein-coupled receptors.
In conclusion, PSAPD might not only cause accumulation of some sphingolipids, but also it can cause neuronal survival crisis.