Background: P450 Oxidoreductase (POR) Deficiency(PORD) represents the most complex form of congenital adrenal hyperplasia. It usuallycauses genital ambiguity in both sexes, and eventually peculiar skeletal malformations resembling Antley-Bixler syndrome. Co-occurrence of POR deficiency and Argininosuccinatelyase Deficiency (ALD)in the samepatient born to non-consanguineous parents has never been reported.
Case report: A male patient was born at term to non-consanguineous parents, with a weight of 3.35 kg. He was diagnosed with ALD (genotype: homozygous p.V178M mutation) at the age of 3 years, following diagnosis in his older brother. Despite good compliance to diet, during follow-up the child developed epilepsy (7 years of age), keratoconus (7.5 years of age), optic and auditory nerve atrophy (8 and 11 years, respectively), the latter being not typical of ALD.He came to our attention at the age of 17.4 years because of short stature (Height -2.02 SDS; target height 0.46 SDS), delayed puberty (pubic hair stage 2, testicular volume 10 ml bilaterally; normal penile length) and bone age of13 years. No skeletal malformations were detected.Laboratory work-up revealed: LH(14.3 mU/ml), FSH (16.1 mU/ml), testsosterone (100 ng/dl), DHEA-S 41 ug/dl (80560), androstenedione <0.3 ng/ml (1.13.5), ACTH (222 pg/ml), 17-OHP (28.75 ng/ml), progesterone (21.1 ng/ml), normal electrolytes, renin 36.4 pg/ml (0.920). Synacthen test showed suboptimal cortisol response (peak Cortisol 69 ng/ml), so that the patient was started on hydrocortisone. Urinary steroid profile was suggestive ofcombined signs of 21-hydroxylase and 17-hydroxylase deficiency, typical of POR deficiency. Genetic analysis of the POR gene showed homozygous p.N82I mutation, identified in heterozygosis in both parents. Given the lack of progression into puberty, the boy has been started on testosterone.
Conclusions: This is the first description of POR deficiency in a patient with Argininosuccinatelyase Deficiency. Our patient presented with a mild phenotype mainly characterized by delayed puberty underlying the phenotypc heterogeneity of POR gene mutations.
18 - 21 May 2019
European Society of Endocrinology