Medicine:Combined saposin deficiency
| 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 |
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]
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 a 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’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.[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]
References
- ↑ 1.0 1.1 1.2 1.3 "Entry - #611721 - COMBINED SAPOSIN DEFICIENCY; PSAPD - OMIM" (in en-us). https://omim.org/entry/611721.
- ↑ Hulková, H.; Cervenková, M.; Ledvinová, J.; Tochácková, M.; Hrebícek, M.; Poupetová, H.; Befekadu, A.; Berná, L. et al. (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. https://academic.oup.com/hmg/article-abstract/10/9/927/2901567?redirectedFrom=fulltext&login=false.
- ↑ 3.0 3.1 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. PMID 36969110.
- ↑ "Orphanet: Encephalopathy due to prosaposin deficiency". https://www.orpha.net/en/disease/detail/139406.
- ↑ Kuchař, Ladislav; Ledvinová, Jana; Hřebíček, Martin; Myšková, Helena; Dvořáková, Lenka; Berná, Linda; Chrastina, Petr; Asfaw, Befekadu et al. (2009). "Prosaposin deficiency and saposin B deficiency (activator-deficient metachromatic leukodystrophy): Report on two patients detected by analysis of urinary sphingolipids and carrying novel PSAP gene mutations" (in en). American Journal of Medical Genetics Part A 149A (4): 613–621. doi:10.1002/ajmg.a.32712. ISSN 1552-4833. PMID 19267410.
- ↑ 6.0 6.1 6.2 6.3 "Orphanet: Encephalopathy due to prosaposin deficiency". https://www.orpha.net/en/disease/detail/139406.
- ↑ "Orphanet: Clinical signs and symptoms". https://www.orpha.net/en/disease/sign/139406.
- ↑ "Saposins: structure, function, distribution, and molecular genetics". https://www.jlr.org/article/S0022-2275(20)40540-1/pdf.
- ↑ 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. https://www.sciencedirect.com/science/article/abs/pii/S1047847718301692.
- ↑ 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. PMID 25130661.
- ↑ Meyer, Rebecca C.; Giddens, Michelle M.; Schaefer, Stacy A.; Hall, Randy A. (2013-06-04). "GPR37 and GPR37L1 are receptors for the neuroprotective and glioprotective factors prosaptide and prosaposin". Proceedings of the National Academy of Sciences 110 (23): 9529–9534. doi:10.1073/pnas.1219004110. PMID 23690594. Bibcode: 2013PNAS..110.9529M.
- ↑ Harzer, K.; Paton, B. C.; Poulos, A.; Kustermann-Kuhn, B.; Roggendorf, W.; Grisar, T.; Popp, M. (1989-10-01). "Sphingolipid activator protein deficiency in a 16-week-old atypical Gaucher disease patient and his fetal sibling: Biochemical signs of combined sphingolipidoses" (in en). European Journal of Pediatrics 149 (1): 31–39. doi:10.1007/BF02024331. ISSN 1432-1076. PMID 2514102. https://link.springer.com/article/10.1007/BF02024331.
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