Endocrine Abstracts

Background

Cytochrome P450 oxidoreductase (POR) deficiency is an autosomal recessive steroidogenesis disorder similar to combined deficiencies of 17a-hydroxylase, 17, 20-lyase, 21-hydroxylase. POR deficiency (PORD) is a very rare type of congenital adrenal hyperplasia(CAH) characterized by sexual development disorders and skeletal anomalies. We present a case that was evaluated with a prediagnosis of nonclassical CAH and was found to have a heterozygous mutation in the POR gene.

Case report

A 23 years old male patient applied to our clinic with complaint of excessive hair. These symptom had started on her arms and legs at 6 years old, appeared on her back at 8 years old, then spread to all over the body. He has reached his final adult height at about 15 years old. He had no history of chronic illness, his 47 years old mother and 56 years old father were consanguineous. On physical examination, his blood pressure was 120/80mm/hg, height was 161cm, the length of the penis was 9.5cm and testicular volume was 20 ml. Laboratory tests were as follows; glucose 89 mg/dl (70-99), sodium 138 mEq/l (132-146), potassium 4.7 mEq/l (3.5-5.5), cortisol 20.3 µg/dl (5.2-22.4), ACTH 37.8 pg/ml (<46), TSH 1.6 mU/l (0.55-4.78), sex hormone binding globulin 7 nmol/l (10-57), FSH 3.2U/l (1.4-18.1), LH 6.9U/l (1.5-9.3), progesterone 1.26 µg/l (0.28-1.22), total testosterone 383 ng/dl (164-753), dehydroepiandrosteronesulfate 698.72 µg/dl (34.5-568.9), 17-alpha-hydroxyprogesterone (17-OHP) 1.22 ug/l, free testosterone 26.6 pg/ml (15-50), androstenedione 13.5 nmol/l (2.1-10.8). Maximum 17-OHP was 3.36 mg/l after ACTH-stimulation. Abdominal magnetic resonance imaging showed normal adrenal glands. Scrotal ultrasonography was normal. Bone age was 18 years. Genetic testing revealed that the patient was heterozygote for c.461A > T(p.Asp154Val) mutation in exon 5 of POR gene while CYP21A2, CYP17A1, CYP11B1, HSD3B2, STAR genes were normal. Subsequent genetic testing of parents showed that his mother also had POR(NM_000941.3):c.461A > T(exon5) heterozygote mutation, while there was no mutation in his father.

Conclusion

A great number of POR variants affecting more than 130 amino acids in the POR protein have been reported. There is clinical heterogeneity in patients with POR gene mutations, making the diagnosis difficult. Considering that the POR gene mutation shows ethnic differences, we think that the determination of variant cases in our society will clarify its importance in this case in the future.

Keywords: cytochrome P450 oxidoreductase, POR heterozygote mutation.