We report a case of a 16 years old girl who presented sequentially with primary amenorrhoea, hypertension and hypokalaemia. Eight years later, she was finally diagnosed with 17alpha-hydroxylase deficiency congenital adrenal hyperplasia. Previous antihypertensive medications were stopped. Hydrocortisone alone successfully maintained normotension and normokalaemia.
Adrenal Hyperplasia, Congenital/*diagnosis ; Adrenal Hyperplasia, Congenital/*etiology ; Diagnosis, Differential ; Hypertension/etiology ; Hypogonadism/etiology ; Hypokalemia/etiology ; Steroid Hydroxylases/*deficiency

Objective To analyze the clinical features of 17α-hydroxylase deficiency and explore the appropriate timing and methods of surgical treatment. Methods We retrospectively analyzed the clinical data of patients with complete 17α-hydroxylase deficiency,containing Y chromosome material in their karyotype,adimitted to Peking Union Medical College Hospital from January 2004 to December 2014. Results Thirty patients with complete 17α-hydroxylase deficiency were included. Their social gender were all female and the mean age at diagnosis was (16.1±2.7) years. Twenty-six patients (86.7%) presented with primary amenorrhea and hypertension. The development of secondary sexual characteristics was poor and their uterus was absent. The levels of gonadotropin,progesterone,and adrenocorticotropic hormone were elevated in all patients and the levels of estradiol,testosterone,and cortisol were decreased. All patients had undergone laparoscopic gonadectomy. Most (86.7%) of the gonads were located in abdomen,while 13.3% were in inguinal canal. Histopathology confirmed that gonadal malignancy was obsetved in two patients (6.7%): one with leydig cell tumor and the other with sertoli cell tumor. Conclusions Patients with complete 17α-hydroxylase deficiency have specific clinical features. Early diagnosis and timely laparoscopic gonadectomy are critical to prevent gonadal malignancy.
Adolescent ; Adrenal Hyperplasia, Congenital ; complications ; surgery ; Amenorrhea ; etiology ; Female ; Humans ; Hypertension ; etiology ; Karyotyping ; Retrospective Studies ; Steroid 17-alpha-Hydroxylase

Adrenal Hyperplasia, Congenital ; complications ; metabolism ; Body Height ; Growth Disorders ; etiology ; Humans ; Risk Factors ; Steroid 21-Hydroxylase ; metabolism

OBJECTIVECongenital lipoid adrenal hyperplasia (CLAH) is an autosomal recessive inherited disorder, characterized by deficiency of adrenal and gonadal steroid hormones. Recent studies have shown that mutations in the gene for steroidogenic acute regulatory protein (StAR) cause this most severe genetic disorder in steroid hormone biosynthesis. StAR is a mitochondrial protein promotes cholesterol transfer from outer mitochondrial membrane to the inner mitochondrial membrane, where the cholesterol serves as a substrate for P450scc and initiates steroidogenesis. So far, more than 30 different mutations in the StAR gene have been found in the patients with CLAH from various ethnic groups. None of CLAH patients in the Chinese population has been previously reported. In the present study we analyzed the StAR gene in a Chinese patient with CLAH.

METHODSThe patient who was a 19-yr-old phenotypic female, has a 46, XY karyotype. Endocrinological evaluation was performed. Genomic DNA samples were abstracted from the bloods of the patient and his parents. Polymerase chain reaction (PCR), direct DNA sequencing, family analysis and restriction enzyme digestion analysis were used to detect and confirm the mutations of StAR gene.

RESULTSEndocrine evaluation of the patient showed extremely elevated basal concentrations of serum ACTH and gonadotropin and minimal concentration of gonadal steroids. An ACTH stimulation test indicated basal serum dehydroepiandrosterone and 17-hydroxyprogesterone were lower than normal detectable range and had no obvious increase after the ACTH stimulation. Automatic sequencing of 7 exons of the StAR gene with the polymerase chain reaction products of the genomic DNA revealed compound heterozygous for a novel nonsense mutation Q77X in exon 3 and the frameshift mutation 838delA in exon 6. The father carried Q77X mutation and the mother carried 838delA mutation. The restriction enzyme site of the Q77X mutation was examined by endonucleotidase BfaI. Furthermore, this mutation was not found in a series of 20 alleles of normal individuals.

CONCLUSIONQ77X is the novel mutation found in the patient with CLAH. Q77X and 838delA compound mutations could inactivate the StAR function and give rise to clinically manifest CLAH. This case is the first Chinese patient with CLAH identified by molecular genetic analysis. DNA-based analysis of StAR gene will be helpful for the diagnosis of CLAH.

Adrenal Hyperplasia, Congenital ; complications ; genetics ; Adrenal Insufficiency ; etiology ; Female ; Genotype ; Gonadal Steroid Hormones ; deficiency ; Humans ; Mutation ; Phenotype ; Phosphoproteins ; genetics ; Young Adult