Delayed Diagnosis of a 17-Hydroxylase/17,20-Lyase Deficient Patient Presenting as a 46,XY Female: A Low Normal Potassium Level Can Be an Alerting Diagnostic Sign

Abstract

17-hydroxylase/17,20-lyase deficiency (17-OHD), a rare autosomal recessive defect in adrenal and gonadal steroidogenesis, causes absence of secondary sexual characteristics and frequently associated with hypertension and hypokalemia. Here, we report a 46,XY case who had normal potassium levels and no hypertension. Our patient was a 2.5-year-old female admitted with female external genitalia and inguinal swelling. Pathology of biopsy revealed that this gonad was a testis. Karyotype was 46,XY. She had no hypertension and no hypokalemia. Serum luteinizing hormone and follicle-stimulating hormone levels were high; testosterone, dehydroepiandrosterone sulfate, and androstenedione were low. Human chorionic gonadotrophin stimulation resulted in partial testosterone response. She was initially diagnosed as partial gonadal dysgenesis or testosterone synthesis defect. In her follow-up after noticing low normal potassium levels at age 9 years, progesterone level was measured and detected to be high. Adrenocorticotropic hormone-stimulated steroid measurements were consistent with 17-OHD. Genetic analyses revealed p. R96Q (c.287G>A) homozygous mutation on exon 1 of CYP17A1 gene. In conclusion, evaluation of 46,XY disorder of sex development patients must include serum potassium levels, and near low levels of potassium levels should also suggest 17-OHD despite absence of hypertension or remarkable hypokalemia. Testosterone synthesis defects must be excluded before establishing the diagnosis of partial gonadal dysgenesis.

Case report: 17α− hydroxylase deficiency due to a hotspot variant and a novel compound heterozygous variant in the CYP17A1 gene of five Chinese patients

“…Research suggests that 10–15% of 17OHD patients do not have hypertension or hypokalemia ( 14 ) and the extent of hypertension and hypokalemia varies from case to case. Thus, 17OHD should not be ruled out because of the absence of hypertension or remarkable hypokalemia ( 15 ).…”

An Asian case of combined 17α-hydroxylase/17,20-lyase deficiency due to homozygous p.R96Q mutation: A case report and review of the literature

“…In 2017, Camtosun et al. ( 7 ) reported another misdiagnosed case in Turkey, who presented with inguinal hernia on the right side at 2.5 years old, which was found to be testicular tissue. Given the lack of hypertension and hypokalemia, the initial diagnosis was partial gonadal dysgenesis or testosterone synthesis defect.…”

“…In 2006, Brooke et al described the first case of p.R96Q mutation on exon 1 of the CYP17A1 gene in an Arabian female patient, who demonstrated clinical and biochemical features of combined 17alpha-hydroxylase/17,20lyase deficiency (4). Since then, several cases of 17-OHD due to p.R96Q mutation have been reported worldwide (5)(6)(7)(8). Herein, we report the first Asian case of 17-OHD, caused by a p.R96Q mutation in the CYP17A1 gene.…”

Multidisciplinary team management of 46,XY 17α-hydroxylase deficiency: a case report and literature review

“… 3 However, remarkable variation in the severity of the clinical manifestation of the same mutation has been noted. 3 , 12 , 14 , 15 In recent years, some patients with incomplete 17OHD have been found to be normokalemic and normotensive, with breast development and ambiguous external genitalia. 16 , 17 Because of the heterogeneity of the clinical manifestations of 17OHD, the incidence of misdiagnosis or missed diagnosis early in the process is very high.…”

“…4 In patients with 46,XY 17OHD, normal secretion of anti-Mu¨llerian hormone in the embryonic stage causes regression of the Mu¨llerian ducts (fallopian tubes, uterus, and upper third of vagina). 12 The internal genitalia are hypoplastic testes, but the external genitalia are infantile female or ambiguous due to the absence of androgen, and no secondary sexual signs or typical sexual development occurs during the pubertal years. 13 The phenotypic severity of 17OHD depends primarily on whether the activities of enzymes are completely or partially lost, which depends on the type and localization of the mutation in the CYP17A1 gene.…”