A Chinese girl with delayed puberty due to 17α-hydroxylase deficiency: the diagnosis, treatment and monitoring approach.

Summary: 17α-hydroxylase deficiency (17α-OHD) is a rare form of congenital adrenal hyperplasia. We report the case of a teenage girl with 17α-OHD who presented with delayed puberty, hypergonadotropic hypogonadism and hypertension. We illustrate the clinical approach in workup, the subsequent management and monitoring of this rare condition. Learning points: 17α-hydroxylase deficiency (17α-OHD) should be considered as a rare yet important differential diagnosis of girls with delayed puberty and elevated gonadotropins. Urine steroid profile, plasma aldosterone and renin levels should be assessed in adolescent girls with hypergonadotropic hypogonadism, after the exclusion of more common conditions, e.g. Turner syndrome. Inhibiting deoxycorticosterone (DOC) release by partial glucocorticoid replacement, counteracting DOC's mineralocorticoid effects by antagonists (such as eplerenone or spironolactone) as well as sex hormone replacements constitute the major backbone in the management of 17α-OHD.

Nephrogenic syndrome of inappropriate antidiuresis - An ethnically, genetically and phenotypically diverse disorder: First report in a Chinese adult and review of published cases.

BACKGROUND: Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a rare inherited disorder characterised by hyponatraemia. To date, most reported cases are Caucasians with gain-of-function variants in AVPR2, an X-linked gene which encodes the vasopressin V2 receptor (V2R). Recently, germline gain-of-function variants in the stimulatory G protein α-subunit (Gsα) were reported to cause dominantly inherited NSIAD. CASE REPORT: We report the first Chinese adult diagnosed with NSIAD. He was found to be hemizygous for R137C-V2R, the most prevalent pathogenic variant among Caucasians. After the genetic diagnosis and counselling on the importance of fluid restriction, he had no recurrence of hyponatraemia to date. LITERATURE REVIEW: Case reports of NSIAD published in the English literature in PubMed were reviewed to summarise the genetic and phenotypic heterogeneity of this disorder. CONCLUSION: NSIAD is ethnically, genetically and phenotypically diverse. The diagnosis should especially be considered in young patients with otherwise unexplained hyponatraemia. Target analysis of R137C-V2R should make the diagnosis in most cases. Genetic testing could confirm the diagnosis, motivate adherence to treatment, offer the possibility of genotype-guided therapy, and allow cascade screening to prevent hyponatraemia.