Combined saposin deficiency
Medical condition
From Wikipedia, the free encyclopedia
Combined Saposin Defiency is a very rare metabolic and genetic disorder that is caused by the mutation in a gene PSAP.[1] This disease belongs to Lysosomal Storage Diseases(LSDs).[2] 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.[3]
| Combined Saposin Deficiency | |
|---|---|
| Other names | Prosaposin Defiency, Combined Sap Deficiency, PSAPD |
| |
| 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 |
Cause
PSAPD is caused by mutations in a PSAP gene, which is located on the long arm of chromosome 10 (10q22.1).[1]
PSAPD is inherited in an Autosomal Recessive fashion.[4][5]
Symptoms
Symptoms usually start in infancy or in neonatal age.[6] 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.[1][7]
Optic atrophy was only reported in 1 patient[1]
Pathophysiology
It is 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.[8][9]
According to one study, Prosaposin might be involved in neuron and glial protection by extracellular secretion and activation of some G protein-coupled receptors.[10][11]
In conclusion, PSAPD might not only cause accumulation of some sphingolipids, but also it can cause neuronal survival crisis (by mechanism mentioned above).[3]
Prevalence
Prevalence is unknown but 10 cases of this diseases had been reported.[6]
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.[6]
Prognosis
Unfortunately, prognosis is poor for this disease.[6]
History
It was first reported by Harzer et al. in 1989[12]