Clinical And Genetic Study Of17α-hydroxylase/17,20-lyase Deficiency

Background and Objective:17α-hydroxylase/17,20-lyase deficiency is a rare causeof congenital adrenal hyperplasia, clinicians understand less about it, and it is easilymisdiagnosed. The aim of the study is to have a better understanding of the etiology，pathogenesis, pathophysiology, genetic features, clinical manifestations, diagnosis andtreatment of the17α-hydroxylase/17,20-lyase deficiency, and to improve therecognition of the disease.Methods: Clinical features and laboratory data were collected from one patient with17α-hydroxylase/17,20-lyase deficiency in our hospital. CYP17A1gene detectionwas carried out in the patient. Literature about the disease was reviewed.Results:1.The patient presented with primary amenorrhea, lack of secondary sexualdevelopment, hypertension and repeated limb weakness. The laboratory examinationsrevealed decreased plasma cortisol and increased adrenocorticotropic hormone;decreased estradiol and dehydroepiandrosterone-sulfate and increased gonadotropin;decreased17-hydroxyprogesterone and increased progesterone; decreased serumpotassium, plasma rennin activity and aldosterone. Ultrasonography revealed aninfantile uterus. CT scan showed bilateral adrenal hyperplasia. According to theclinical presentations and auxiliary examination, the patient was considered ascomplete combined17α-hydroxylase/17,20-lyase deficiency.2. CYP17A1analysis revealed that the patient was a compound heterozygotemutation in exon8of D487_F489del and in exon6of TAC329AA. The deletion of9bases GACTCTTTC (1459–1467) in exon8results in the deletion of three aminoacids of Asp–Ser–Phe at the position487–489. The replacement of nucleotide TACby AA at codon329in exon6causes a missense mutation of Tyrâ†'Lys at codon329and a frame-shifting, resulting in a premature stop codon at codon418. Both of themhave been proved to completely abolish the activities of17α-hydroxylase and17,20-lyase.Conclusions:1.17α-hydroxylase/17,20-lyase deficiency should be considered in phenotypic female who present with primary amenorrhea, or lack of secondary sexualdevelopment after the puberty, especially combined with hypertension andhypokalemia. Detection of CYP17A1gene may help to make diagnosis.2. According to the clinical presentations, auxiliary examination and genesequencing results, the patient was diagnosed as complete combined17α-hydroxylase/17,20-lyase deficiency. Combined with the literature,D487_F489del and TAC329AA mutations are common mutations of17α-hydroxylase/17,20-lyase deficiency in China.