Hyperprolinemia in schizophrenia:

Hyperprolinemia in schizophrenia:

Hyperprolinemia in schizophrenia: Underlying cause or potential result

Azaa Elshafi Khadir-MBBS. Msc. University of Khartoum, Sudan

Mohamed Abdalhameed Alnor- MBBS. Msc. MD. University of Khartoum, Sudan

Muntaser El Tayeb Ibrahim, B.Sc. M.Sc. Ph.D. University of Khartoum, Sudan

 

Introduction

Metabolic defects related to Schizophrenia are explained either by the unhealthy life style of schizophrenic patients including poor diet and sedentary behavior or the use of antipsychotic drugs that may contribute to metabolic disorders including obesity, diabetes mellitus, and cardiovascular disease. However genes and metabolites related to energy metabolism that may be altered in schizophrenia, appear to have changed rapidly during recent human evolution, probably as a result of positive selection. Some metabolic conditions and enzymatic deficiencies may in fact contribute to the pathogenesis of the disease including Proline dehydrogenase (PRODH).

Hereditary hyperprolinemia: type I abnormality in the proline oxidizing enzyme and type II caused by a deficiency of Δ-1-pyrroline-5-carboxylate dehydrogenase (P5CDh). The underlying mechanism regarding these two types may affect neurotransmitters (GABA), also stress conditions generate ROS which can mediate apoptosis.

 

Methods

 A family with tow sibling affected with schizophrenia and on antipsychotic treatment and three other siblings with learning disability and one healthy control were sampled. Whole Exome sequencing was carried out for the tow patients and one healthy control.

 

Results, Discussions and Conclusion

Of the 31deleterious mutations with high impact and associated with schizophrenia identified through the pipeline one mutation  in PRODH was of interest, as mutations in this gene was associated with both hereditary hyperprolinemia and schizophrenia. In investigating the genetic of schizophrenia a major question arises; Is the disease a secondary psychiatric manifestation following a course of metabolic disorder (syndromes) or is the underlying causes of schizophrenia that explain its pathophysiology  mainly a defect in metabolism? This could be answered by further understanding the action of PRODH, it`s genetic and protein interaction, related signaling pathways and epigenetic changes. Further testing to confirm the presence of high Proline or its metabolites in blood of a wider sample is recommended.

 

 

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