Clinical Study And Literature Review On 23 Cases With 17α-hydroxylase/17,20-lyase Deficiency

Background and objective:Congenital adrenal hyperplasia（CAH）is a disease caused by genetic defects in some enzymes which are necessary for synthesizing cortisol.17α-hydroxylase/17,20-lyase deficiency（17OHD）is a rare type of congenital adrenal hyperplasia（CAH）diseases,<1% of all CAH cases.17α-hydroxylase and 17,20-lyase are a kind of microsomal cytochrome P450c17,encoded by CYP17A1 gene.CYP17A1 gene mutation impairs the activity of both enzymes.Depending on the extent of damage to 17 hydroxylase and 17,20 lyase,the combined defect could be divided into complete and partial 17 OHD.It′s easy to be misdiagosed for the atypical clinical manifestations and rarity,as well as the physician’s neglect in sexual examination.Therefore,this current study intends to analyze the clinical characteristics,laboratory datas and genetic analysis of the 23 identified 17 OHD patients from china,so as to improve the recognition of this disease.Patients:23 patients were diagnosed with 17 OHD in the First Affiliated Hospital of Zhengzhou University from May 2011 to February 2018.Methods:1.Peripheral venous blood was extracted in the morning and serum electrolytes,gonadal steroids,gonadotropin,glucocorticoid and mineralocorticoid were detected.Some cases performed the dual-energy X-ray absorptiometry to detect the bone density.Some cases had performed the karyotype analysis.All patients performed the ultrasound of adnexa uteri and CT scan.2.Peripheral blood of genomic DNA was extracted.PCR amplification combined with next generation sequencing were used to detect the mutation of CYP17A1 gene.3.At present,there is no unified diagnostic standard for 17 OHD.According to previous literature,the main diagnostic points are summarized as follows: 3.1 Complete 17OHD: the patients manifest as female genital infantilism,absented secondary sexual characteristics,primary amenorrhea,hypertension.The estradio,testosterone and cortisol are lower while the gonadotropin,corticotropin and progesterone are elevated.And they also have hypokalemia and low plasma renin activity.The ultrasound in males indicates absence of adnexa uteri,and testicle can be found in the enterocoelia or inguinal area.In females,it indicates immature uterus.CT scan shows adrenal hyperplasia.3.2 Partial 17OHD: the patients can have normal blood pressure and serum potassium,and also can have hypertension and hypokalemia.Female can have spontaneous secondary sexual characteristics and menstruation,while male can be shown as hermaphroditism.The progesterone is elevated,while the estradio,testosterone and renin activity are lower.The corticotropin can be higher than normal or in the normal range.Dehydroepiandrosterone-sulfate are lower.Results:1.There were 19 cases with complete 17 OHD and 4 cases with partial 17 OHD.Among the 19 patients with complete 17 OHD,10 patients had karyotypes of 46,XY,and 6 patients had karyotypes of 46,XX,while 3 patients did not had their karyotypes detected.Among the 4 patients with partial 17 OHD,3 had karyotypes of 46,XX,and 1 had karyotype of 46,XY.2.19 patients with complete combined defect had typical clinical presentation including absented secondary sexual characteristics,primary amenorrhea,hypertension and hypokalamia.The labotary tests showed that estradio,testosterone and cortisol were lower while the gonadotropin,corticotropin and progesterone were elevated.TAC329 AA homozygous mutation,IVS1+2T>C and c.775₇76delAT complex heterozygous mutation were respectively found in 2 cases with complete combined 17 OHD.In the 4 cases with partial combined defect,3 female（46,XX）showed spontaneous menstrual and primary infertility,two of them got successful pregnancy with assisted reproductive technology,and 1 male（46,XY）showed hermaphrodism,clitoral hypertrophy and urethro-vaginal fusionall.All the 4 cases with partial combined defect had high concentrations of progesterone,lower gonadal hormones and dehydroepiandrosterone-sulfate.The cortisol were lower or in the normal range,while the corticotropin were elevated or in the normal range.TAC329 AA heterozygous mutation were found in the 4 cases.Conclusions:1.For patients with primary amenorrhea,absented secondary sexual characteristics combined with hypertension and hypokalamia,attention should be paid to the identification of 17 OHD.2.Heterozygous or homozygous mutation of TAC329 AA may be the genetic and molecular basis for determining whether these patients present as partial or complete defect.3.The elevating plasma progesterone in non-pregnancy combined with lower gonadal hormones and dehydroepiandrosterone-sulfate is the main character of patients with partial 17 OHD.4.Less severe patients with partial 17 OHD can get successful pregnancy with assisted reproductive technology.