ESPE Abstracts

Background: X-linked hypophosphataemic rickets (XLH) is a genetic disorder, characterized by hypophosphatemia and caused by a mutation in the phosphate regulating endopeptidase homolog, X-linked (PHEX) gene which leads to overexpression of fibroblast growth factor 23 (FGF23).1,2 Conventional therapy, supplementation with oral phosphate and vitamin D analogs, does not treat the underlying cause of the disorder and is associated with poor treatment ad...

A broad spectrum of human diseases, including abnormalities in steroidogenesis, are caused by mutations in the NADPH cytochrome P450 oxidoreductase (POR) (1-4). Human POR is a diflavin reductase that transfers electrons from NADPH to small molecules, non-P450 redox partners and cytochrome P450 proteins in the endoplasmic reticulum. Cytochrome P450 proteins perform a very wide range of reactions, including metabolism of steroids, drugs and other xenobiotics. Therefore, genetic ...

Background: Recombinant GH (rGH) treatment is approved in many countries for treatment of short stature in a number of childhood diagnoses. rGH was first introduced in Kuwait in the 1990s. Since its introduction, there has been no reported data on the clinical profile of treated children. There is a huge gap in knowledge of use and response to Paediatric rGH therapy in Kuwait and the region.Objective and hypotheses: The objective of this study is to repo...

Background: The cytochrome P450 CYP17A1 plays a vital role in regulating adrenal androgen production. The 17,20 lyase activity of CYP17A1 is key for androgen regulation. The orteronel and galeterone are known to inhibit 17,20 lyase activity however the detailed mechanisms of the inhibition of CYP17A1 activities remain unknown. These inhibitors have been developed to treat the castration resistant prostate cancer (CRPC) but little is known about their effects on adrenal androge...

Background: Aromatase (CYP19A1) a member of cytochrome P450 protein family is a major steroid metabolizing enzyme which converts androgens to estrogens. Mutations in aromatase can lead to autosomal recessive aromatase deficiency. An R192H mutation in CYP19A1 described earlier caused severe phenotype of aromatase deficiency with regressive virilization of the 46,XX new-born, but without signs of androgen excess during pregnancy. Computational studies suggested that R192H disrup...

Background: Cytochromes P450 proteins metabolize several steroid hormones, drugs and xenobiotics. All cytochromes P450s in the endoplasmic reticulum require P450 oxidoreductase (POR) for their catalytic activities. Earlier it has been shown that mutations in POR cause metabolic disorders of steroid hormone biosynthesis and also affect some drug metabolizing P450 activities. We aimed to characterize the mutations identified in nonclinical samples to access their effects on ster...

Background: The steroidogenic enzyme aromatase (CYP19A1) is a protein located in endoplasmic reticulum (ER) that catalyzes the conversion of androgens to estrogens. Both deficiency and excess of aromatase activity lead to disease states implicating its role in human biology. Cytochrome P450 (CYP) enzymes in ER use reduced nicotinamide adenine dinucleotide phosphate through cytochrome P450 oxidoreductase (POR) for their metabolic activities. Mutations in POR cause disorders of ...

Background: A broad spectrum of human diseases including abnormalities in steroidogenesis is caused by mutations in the NADPH P450 oxidoreductase (POR). POR transfers electrons from NADPH to several small molecules, non-P450 redox partners and all microsomal cytochrome P450 proteins. POR disruption affects all partners with disastrous consequences and POR knock-out mice are embryonically lethal. A number of POR mutations and polymorphisms have been characterized from patients ...

Background: X-linked hypophosphatemia (XLH) is a rare, often debilitating genetic disorder caused by mutations in the phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) that is characterized by excess fibroblast growth factor 23 (FGF23), hypophosphatemia, skeletal deformities, and growth impairment.1,2 Conventional therapy with the combination of phosphate and active vitamin D is associated with poor treatment adh...

Introduction: Familial chylomicronaemia syndrome (FCS) is a rare autosomal recessive disorder caused by mutations in lipoprotein lipase, resulting in the accumulation of chylomicrons in plasma and therefore hypertriglyceridemia. Elevated triglycerides (TG) cause several complications, the most serious one is recurrent pancreatitis. The mainstream of management is a fat-restricted diet, followed by supplementing with Omega-3 fatty acids. Fenofibrate, and statin...