Introduction: X-linked adrenal hypoplasia congenita (AHC) is caused by mutations of the NR0B1 gene encoding DAX1 on chromosome Xp21. AHC also occurs as part of a contiguous gene deletion syndrome together with Duchenne muscular dystrophy, glycerol kinase deficiency (GKD), mental retardation, or a combination of these conditions. Here, we report a male 5 years old with AHC who presented with adrenal insufficiency, GKD, and duchenne muscular dystrophy due to a mutation in the DAX-1 gene.
Case: A 5 years old male patient who presented with vomiting, bruising, fainting, growth and failure to thrive was hospitalized. He was dehydrated, lethargic. His external genitalia was well developed with intrascrotal testes of 2 ml in volume. There was skin hyperpigmentation. The patient underwent a detailed clinical investigation including genetic testing. The initial laboratory tests showed sodium: 126 meq/l, potassium: 7.3 meq/l, glucose: 64 mg/dl, blood urea nitrogen: 32 mg/dl, basal cortisol level: 1.2 μg/dl, adrenocorticotropic hormone (ACTH) level: >1250 pg/ml, 17 hydroxyprogesteron (17-OHP): 0.1 ng/ml, dehydroepiandrosterone-sulphate: 0.1 μg/dl, testosterone: 0.1 ng/ml. Hydrocortisone, fludrocortisone and sodium chloride supplement were initiated. This treatment corrected electrolyte abnormalities and the patient improved. Adrenal glands were not visualized on abdominal ultrasound. The diagnosis was AHC. Further, we investigated for contiguous deletion syndrome. His creatinine phosphokinase (CK) (7592 U/L, normal: 35195) and triglyceride (TG) (1045 mg/dl normal: 0200) levels were elevated. Molecular analysis of the NR0B1 (DAX1) gene revealed a complete deletion. With these findings, we made a diagnosis of Xp21 contiguous gen deletion syndrome.
Conclusion: DAX-1 deficiency should be kept in mind in male patients with primary adrenal insufficiency without congenital adrenal hyperplasia. Furthermore, CK and TG levels should be measured in all male patients with adrenal hypoplasia. These simple tests may help to make early diagnosis and appropriate genetic counselling for next pregnancy.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology