A novel missense mutation in DAX-1 with an unusual presentation of X-linked adrenal hypoplasia congenita

Horm Res. 2007;68(1):32-7. doi: 10.1159/000099835. Epub 2007 Feb 16.


A male presented at age 2.2 years with a 6-week history of intermittent vomiting and hyperpigmentation. Investigations showed salt wasting with hyperkalaemia, a grossly impaired cortisol response to ACTH stimulation, elevated renin and ACTH. Family history revealed that two maternal uncles had died soon after birth. A third uncle failed to thrive during infancy but improved with a course of cortisone, then being untreated until further investigation revealed adrenal insufficiency. A fourth uncle died aged 10 days, with urinary salt loss and hypoplastic adrenal glands at postmortem. Molecular studies on the proband, his mother, maternal grandmother, and surviving uncle showed a novel C to G substitution at nucleotide position 794 (missense mutation T265R) in the DAX1 (NR0B1) gene. The proband has responded well to steroid replacement but has proved sensitive to 9alpha-fludrocortisone treatment, developing hypertension on a dose of 133 microg/m(2)/day. At 8.8 years he was noted to have testicular volumes of 4 ml, despite no other evidence of secondary sexual development and prepubertal gonadotrophin levels. Novel features of this family include a novel DAX1 mutation, marked variability in age of presentation, hypertension on 'standard' doses of 9alpha-fludrocortisone and mild testicular enlargement.

Publication types

  • Case Reports

MeSH terms

  • Adrenal Glands / abnormalities*
  • Adrenal Glands / physiopathology
  • Adrenal Insufficiency / congenital*
  • Adrenal Insufficiency / drug therapy
  • Adrenal Insufficiency / physiopathology
  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Child, Preschool
  • Cortisone / adverse effects
  • Cortisone / analogs & derivatives
  • DAX-1 Orphan Nuclear Receptor
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / physiology
  • Genetic Diseases, X-Linked / drug therapy
  • Genetic Diseases, X-Linked / physiopathology*
  • Humans
  • Hydrocortisone / therapeutic use
  • Male
  • Mutation, Missense
  • Pedigree
  • Receptors, Retinoic Acid / genetics*
  • Receptors, Retinoic Acid / physiology
  • Repressor Proteins / genetics*
  • Repressor Proteins / physiology
  • Testis / physiopathology*


  • Anti-Inflammatory Agents
  • DAX-1 Orphan Nuclear Receptor
  • DNA-Binding Proteins
  • NR0B1 protein, human
  • Receptors, Retinoic Acid
  • Repressor Proteins
  • 9-fluorocortisone
  • Cortisone
  • Hydrocortisone