Combined saposin deficiency

Combined Saposin Deficiency
Other names	Prosaposin Defiency, Combined Sap Deficiency, PSAPD
File:Autosomal recessive - en.svg
PSAPD is inherited in an autosomal recessive fashion
Symptoms	Respiratory failure, hepatosplenomegaly, poor feeding, myoclonus, hyperkinesia, seizures, leukodystrophy, hypotonia, abnormal eye movement, neuronal loss
Causes	Genetic mutations
Diagnostic method	Genetic testing
Frequency

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(LSDs). Because of complete saposin deficiency, it can cause clinical features of 4 diseases(Gaucher’s Disease, Metachromatic Leukodystrophy, Farber’s Disease, Krabbe’s Disease) to be apparent.

Cause

PSAPD is caused by mutations in a PSAP gene, which is located on the long arm of chromosome 10 (10q22.1).

PSAPD is inherited in a Autosomal Recessive fashion.

File:Protein PSAP PDB 1m12.png

A photo showing structure of Prosaposin

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 (by mechanism mentioned above).

Prevalence

Prevalence is unknown but 10 cases of this diseases had been reported.

Diagnosis

The study of sphingolipids in urine sediment (It shows combined massive elevation of globotriaosylceramide (Gb3), sulphatide and some other sphingolipids) might be useful for a correct orientation towards diagnosis, also bone marrow/liver’s biopsies usually show Gaucher-like macrophages. For the final diagnosis PSAP gene would be tested for mutations.

Prognosis

Unfortunately, prognosis is poor for this disease.

History

It was first reported by Harzer et al. in 1989