Draft:Combined Saposin Deficiency
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 a Autosomal Recessive fashion | |
Cause
[edit]PSAPD is caused by mutations in a PSAP gene, which is located on the long arm of chromosome 10 (10q22.1).[1]
Symptoms
[edit]The symptoms of this disease are (according to OMIM): Respiratory failure, Hepatosplenomegaly, Poor feeding, Myoclonus, Hyperkinetic movements, Clonic seizures, Hypotonia, Leukodystrophy.[4]
Also Optic atrophy was identified only in 1 patient.[4]
Pathophysiology
[edit]It’s known that Prosaposin is a precursor of 4 proteins (Saposin A; B; C; D) and Saposin is a cofactor for many lysosomal sphingolipid metabolising enzymes, Saposin A is needed to stimulate galactocerebroside hydrolysis, Saposin B is needed to stimulate sulphatide hydrolysis and Saposin C is needed for glucocerebroside hydrolysis stimulation, Saposin D function is to stimulate ceramide hydrolysis.[5] [6]
According to one study, Prosaposin might be secreted extracellularly and bind some G protein-coupled receptors to exhibit neuroprotective effects.[7]
In conclusion, PSAPD might not only cause accumulation of some sphingolipids, but also it can cause neuronal survival crisis.[3]
Prevalence
[edit]The prevalence of this is unknown. Only 10 cases had been reported.[8]
Treatment
[edit]This disease doesn’t have a cure, only symptomatic management is available[8]
Reference
[edit]
- ^ a b "Entry - #611721 - COMBINED SAPOSIN DEFICIENCY; PSAPD - OMIM". omim.org. Retrieved 2025-01-07.
- ^ Hulková, H.; Cervenková, M.; Ledvinová, J.; Tochácková, M.; Hrebícek, M.; Poupetová, H.; Befekadu, A.; Berná, L.; Paton, B.C.; Harzer, K.; Böör, A.; Smíd, F.; Elleder, M. (2001-04-15). "A novel mutation in the coding region of the prosaposin gene leads to a complete deficiency of prosaposin and saposins, and is associated with a complex sphingolipidosis dominated by lactosylceramide accumulation". Human Molecular Genetics. 10 (9): 927–940. doi:10.1093/hmg/10.9.927. ISSN 0964-6906. PMID 11309366.
- ^ a b Bhat, Vivek; Thergaonkar, R. W.; Thakur, Manisha; Rajkamal, T. (2023-03-01). "Combined saposin deficiency: A rare occurrence". Medical Journal Armed Forces India. 79 (2): 238–240. doi:10.1016/j.mjafi.2021.01.024. ISSN 0377-1237. PMC 10037043. PMID 36969110.
- ^ a b "Clinical Synopsis - #611721 - COMBINED SAPOSIN DEFICIENCY; PSAPD - OMIM". omim.org. Retrieved 2025-01-07.
- ^ www.jlr.org http://web.archive.org/web/20230428233731/https://www.jlr.org/article/S0022-2275(20)40540-1/pdf. Archived from the original on 2023-04-28. Retrieved 2025-01-07.
{{cite web}}: Missing or empty|title=(help) - ^ Gebai, Ahmad; Gorelik, Alexei; Nagar, Bhushan (2018-11-01). "Crystal structure of saposin D in an open conformation". Journal of Structural Biology. 204 (2): 145–150. doi:10.1016/j.jsb.2018.07.011. ISSN 1047-8477. PMID 30026085.
- ^ Meyer, Rebecca C.; Giddens, Michelle M.; Coleman, Brilee M.; Hall, Randy A. (2014-10-17). "The protective role of prosaposin and its receptors in the nervous system". Brain Research. 1585: 1–12. doi:10.1016/j.brainres.2014.08.022. ISSN 0006-8993. PMC 4529117. PMID 25130661.
- ^ a b "Orphanet: Encephalopathy due to prosaposin deficiency". www.orpha.net. Retrieved 2025-01-07.