Endocrine Abstracts (2006) 11 P138

Resolution of diagnostic uncertainties with DAX-1 gene mutation analysis

P Arundel, R Fisher, C Chu & S Alvi


Leeds Teaching Hospitals NHS Trust, Leeds, West Yorkshire, United Kingdom.


Mutations in the DAX-1 gene are well described in patients with adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism but can be a useful tool in the elucidation of unusual or difficult cases of adrenal insufficiency. As the clinical presentation of congenital adrenal hyperplasia and AHC can be clinically identical, diagnosis in the neonate often depends on the levels of 17-hydroxyprogesterone (17-OHP). If these are unavailable or non-diagnostic, gene analysis can be important.

We present three patients from two unrelated families in whom genetic evaluation both corrected misdiagnoses and also significantly altered long-term clinical management and genetic counselling.

In the first family, a male infant presented with a salt-losing crisis at 3 weeks of age and was erroneously diagnosed with 21-hydroxylase (21-OH) deficiency. DNA analysis of the 21-OH gene was normal, but DAX-1 mutation analysis revealed a single base pair G deletion in codon 183 resulting in a premature stop codon at codon 263. They have subsequently had a second son without the mutation.

In the second family, DAX-1 mutation analysis was carried out on a mother who had lost two sons in infancy with adrenal crises of undetermined aetiology thirty years previously. Her daughter was considering starting a family so the cases were revisited. Inspection of the boys’ medical records revealed post-mortem confirmation of adrenal hypoplasia in one and aplasia in another. Analysis of the mother’s DNA revealed a C to G nucleotide substitution at position 458 causing a stop codon at codon 153.

These 2 families illustrate the need for clinicians to be aware of the possibilities of DAX-1 gene mutations in male patients presenting with hypoadrenalism both in the neonatal period and beyond. It is important to make the diagnosis not only for the patient, but also in order to assess accurately the risks to other family members.

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