Endocrine Abstracts

Triple A syndrome (also known as Allgrove’s syndrome, MIM #231550) is a rare autosomal recessive disorder characterised by ACTH-resistant adrenal insufficiency, alacrima and achalasia. Neurological features may also be present. Various combinations of these features may be present which evolve over time. Triple A syndrome is caused by mutations in the AAAS gene which encodes for the protein ALADIN, a member of the nuclear pore complex, whose function is incompletely understood.

We present the case of an 8-year-old girl who presented with a hypoglycaemic seizure following an overnight fast. Examination revealed palmar skin crease pigmentation. A Synacthen test confirmed primary adrenal insufficiency (basal cortisol 174 nmol/l, stimulated cortisol 173 nmol/l (reference range post stimulation >500 nmol/l), ACTH 2980 ng/l (reference range <55 ng/l)) and glucocorticoid and mineralocorticoid replacement were commenced. Adrenal autoantibodies were negative. Electrolytes, renin and aldosterone levels were normal, and mineralocorticoid replacement was discontinued. There have been no further hypoglycaemic symptoms or seizures. Alacrima was noted at age 9. Now (age 19) she reports nausea, vomiting and swallowing difficulties, which are under investigation. Neurological examination is unremarkable, however she does have moderate learning difficulties and attends a special educational centre.

Genetic testing revealed a homozygous mutation (1144_1147delTCTG) in exon 12 of AAAS gene which causes a frameshift with a premature stop codon (p.Ser382ArgfsX33).

We present a rare case of isolated glucocorticoid deficiency due to Triple A syndrome. This is an evolving condition and patients may develop multiple features over time. We recommend screening for AAAS gene mutations even in the presence of only one of the main symptoms. There is marked clinical variability even in one family and all siblings should be thoroughly investigated. Diagnosis affords screening for the subsequent development of associated features and reduces the risk of presentation with potentially life-threatening adrenal failure.