17?-Hydroxylase/17,20-lyase Deficiency: Two Case Reports And Literature Review

Objective We summarized the diagnosis,treatment,follow-up and genetic counseling experience of two cases with 17-OHD.In order to improve the knowledge on 17-OHD.Methods?1?Clinical and laboratory data of the probands and of their family members were collected.?2?Targeted exon gene-trap and the second generation sequencing associated with gonadal disease?including 164 genes such as AMH,CYB5 A,CYP11A1,CYP17A1,POR,SRY,STAR,SOX9,WNT4,WT1 and so on?,were carried out to detect the mutational gene sequence.Sanger sequencing was performed on the patient and other family members for verification.Additionally,we conducted pathogenicity analysis.?3?Patient's height,weight,blood pressure?BP?,electrolytes,cortisol,adrenocorticotropic hormone?ACTH?and sex hormone were followed up.?4?Experience of diagnosing and treatment of the disease was summarized based on relevant literature and documents.Results?1?Both of these two patients were female in society and external genital sex,they had similar clinical manifestations of hypertension,hypokalemia,a decrease in cortisol,estradiol,testosterone,dehydroepiandrosterone?DHEA?and androstenedione,an increase in ACTH,progesterone,luteinizing hormone?LH?and follicle-stimulating hormone?FSH?.Karyotype of the first case patient was 46,XX,her uterine and ovarian was hypoplasia.Karyotype of the second case patient was 46,XY and she had female external genitalia.Intraperitoneal showed dysplastic testis,which was also confirmed by pathology.?2?Homozygous mutation of c.985₉87delinsAA?p.Y329fs?was found in CYP17A1 in both two patients,their parents and little brother were carriers,neither of them had any symptom or sign,the inheritance pattern of the family was autosomal recessive inheritance.?3?BP and serum potassium of the two patients went back to normal after having oral hydrocortisone daily,and other laboratory index got improved.?4?Review of 27 literatures published between 1989 to 2017,including 101 patients and 203 alleles,indicated that 21.8%?22/101?patients had hypertension,7%?7/101?had hypokalemia,32.7%?33/101?patients had both hypertension and hypokalemia.77.3%?34/44?female patients?46,XX?had dysplasia in secondary sexual characteristics,amenorrhea while 68.4%?39/57?male patients?46,XY?showed female external genitalia.The most common mutations of 17-OHD patients were p.Y329fs?42.3%,41/97?and D487_F489del?27.8%,27/97?in China,H373HL?66.6%,12/18?in Korea,F53?or54?del ?41.7%,5/12?and H373HL?41.7%,5/12?in Japan,W406R?56.8%,25/44?and R362C?36.4%,16/44?in Brazil,E305G?100%,12/12?in Germany,and 4-bp?CATC?dup Ile479?100%,18/18?in Dutch Frieslanders as well as Canadian Mennonites,respectively.Different CYP17A1 mutations could lead to different types of 17-OHD,further studies on relationship between genotype and clinical manifestations of CYP17A1 mutation are needed.Conclusion?1?Manifestations of 17-OHD patients were unspecific while hypertension and hypokalemia was common.Patients with karyotype of 46,XX showed hypoplasia in secondary sexual characteristics and female internal genital organs while patients with karyotype of 46,XY showed female external genitalia and male internal genitalia infantilism.When patients had above features,17-OHD should be considered.?2?Exon gene-trap and the next-generation sequencing combined with Sanger sequencing could help with diagnosis of 17-OHD.The methods were especially beneficial for those whose clinical manifestations were nonspecific,and for genetic counseling.?3?Glucocorticoid replacement therapy could significantly improve patients' clinical symptoms such as hypertension and hypokalemia.?4?The most common mutations in 17-OHD in China were p.Y329 fs and D487_F489del.Further studies on relationship between genotype and clinical manifestations of CYP17A1 mutation are needed.