Clinical features of 9 patients with X-linked adrenal hypoplasia congenita caused by DAX1/NR0B1 gene mutations

Abstract

To study the clinical features of 9 patients with X-linked adrenal hypoplasia congenita (AHC) by gene sequencing so as to provide diagnostic rationales. The patients were 9 cases of X-linked AHC treated at our hospital from July 2007 to June 2009. The clinical manifestations were analyzed. The blood biochemistry tests and the hormone examinations including luteinizing hormone-releasing hormone (LHRH) stimulation tests and human chorionic gonadotropin (HCG) stimulation tests were conducted to evaluate the functions of gonads. And CT scans of adrenal glands and gene tests of DAX1/NR0B1 were performed. Nine AHC patients from 8 families were studied. All patients had DAX1/NR0B1 gene mutations. The main clinical features were: (1) some patients (3 families) had a family history of X-linked recessive inheritance; (2) the ages of onset were all below 10 years old (from 2 month after birth to 9 years old) and ages of being treated at our hospital were from 15 to 34 years old; (3) all patients had adrenocortical hypofunctions, but clinical situations were different, most of them had pigmentation (n = 9), nausea and vomiting (n = 8), hypotension (n = 6), Addisonian crisis (n = 4). Others were debility, hypoglycemia and cold susceptibility. Laboratory tests indicated that all patients had hyponatremia at the onset and higher blood adrenocorticotropic hormone level, lower blood 17-hydroxyprogesterone level compared to normal controls; (4) none of the patients had puberty and there was no responses to LHRH stimulation tests, 3 of them had normal responses to HCG stimulation tests; (5) small bilateral adrenal glands were displayed on CT scans. The main clinical features of X-linked AHC are adrenocortical hypofunction and hypogonadotropic hypogonadism. But the phenotypes vary greatly in different patients. So male children with adrenal cortical hypofunction should be suspected of X-linked AHC and DAX1/NR0B1 gene tests should be performed. The sexual development of the patients also should be followed up.