Clinical Characterization of X-Linked Adrenal Hypoplasia Congenitia in 7 Chinese Children

Presentation Number: SUN 393
Date of Presentation: April 2nd, 2017

Qiong Chen*1, Yongxing Chen1, Fang Liu1, Haiyan Wei1, Haihua Yang1, Ai Huang1, Xiaojing Liu1 and Yun Yan2
1Zhengzhou children's hospital, Zhengzhou, China, 2Children's Mercy Hospital, Overland Park, KS

Abstract

Background: Mutations in DAX1 (dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome gene 1, NROB1) cause X-linked adrenal hypoplasia congenita (AHC). It is a rare disorder of the human adrenal cortex and the clinical expression is variable.

Objective: To study the clinical characterization of 7 Chinese patients with X-linked AHC in Zhengzhou Children's Hospital, Henan, China.

Methods: Seven boys (from different families) with AHC were evaluated in Zhengzhou Children's Hospital, China from 2007 to 2016. All of the patients were screened for NROB1 mutations. Blood biochemistry tests and endocrine evaluations were recorded.

Results: (1) The ages of onset were from birth to 6 years old. Two patients had a family history of X-1inked recessive inheritance; (2) All patients had adrenocortical hypofunctions such as hyperpigmentation, hyperkalemia and hyponatremia. One patient had the sign of pubic hairs at first visit at age of 6 years old. Laboratory evaluation showed that five patients had elevated ACTH, low 17-hydroxypmgesterone and DHEA levels (the initial data of one patient was missing); the size of adrenal glands displayed on abdominal CT and ultrasound was not different compared to normal children, especially after birth. GnRH and HCG stimulation tests were not performed. (3) NROB1 gene mutations were found in all the patients, four of them are novel mutations (c.114_126delCGAACAGCCCCAG, c.1411T>C, c.56delG, c.884T>G). (4) There are three initial misdiagnosed cases among the seven cases at local hospital: two cases were diagnosed as congenital adrenal hyperplasia but their initial data were missing, however, during follow-up one patient showed growth retardation with delayed bone age and another case was diagnosed with precocious adrenarche. The third case was found to have AHC confirmed by genetic testing.

Conclusions: The main clinical characterization of X-linked AHC are adrenocortical hypofunction and hypogonadotropic hypogonadism, but the phenotypes vary. Sexual precocity can also be seen in some cases, secondary to the stimulus exerted by ACTH on melanocortin receptors in Leydig cells. The patients who are diagnosed as congenital adrenal hyperplasia but have growth retardation with delayed bone age should also be suspected as X-linked AHC and genetic testing for DAXI/NROBI mutation should be considered.

 

Nothing to Disclose: QC, YC, FL, HW, HY, AH, XL, YY