An 8-year-old girl presented with a hypoglycaemic seizure and dark cutaneous pigmentation (Figure 1A and B). Response to synacthen stimulation was inadequate and adrenocorticotropic hormone (ACTH) was elevated [basal cortisol 174 nmol/l, stimulated cortisol 173 nmol/l (reference range >500 nmol/l), ACTH 2980 ng/l (reference range <55 ng/l)]. However renin, aldosterone and electrolytes were normal. She had no postural drop in blood pressure. She was commenced on hydrocortisone resolving her pigmentation. A Schirmer's test (Figure 1C) shows no tear production, consistent with alacrima. Artificial tears have been used intermittently for symptomatic relief since age 9. At age 15, she developed swallowing difficulties. A barium swallow (Figure 1D) shows dilatation of the distal oesophagus and almost complete obstruction at the gastro-oesophageal junction, consistent with achalasia. A balloon dilatation procedure is planned with recent work suggesting that outcomes are comparable to that of laparoscopic Heller's myotomy.1 Genetic analysis revealed a homozygous mutation (1144_1147delTCTG) in exon 12 of AAAS gene.
(A) Dark pigmentation especially over extensor surfaces. (B) Dark pigmentation of hands, most marked over interphalangeal creases. (C) Schirmer's test with no visible tear production. (D) Barium meal study showing dilatation of the distal oesophagus and almost complete obstruction at the gastro-oesophageal junction (the bird's beak or rat's tail sign).
AAA syndrome is a rare autosomal recessive disorder characterized by ACTH-resistant adrenal insufficiency, alacrima and achalasia.2 In addition, a variety of neurological problems affecting the central, peripheral and autonomic nervous systems may be present. Dermatological features including palmoplantar hyperkeratosis, cutis anserina, fungiform papillae of the tongue and incomplete dermatoglyphes are present in ∼20% of cases.3 Neurological features may also be present. Various combinations of these features may be present or evolve over time. Marked variability in clinical features is noted even within same kindreds.4
AAA syndrome is caused by mutations in the AAAS gene which encodes for the protein ALADIN, a constituent of the nuclear pore complex whose function is incompletely understood.5,6
AAA syndrome should be considered in patients with atypical primary adrenal insufficiency. Diagnosis allows screening and symptomatic treatment for the subsequent development of associated features and reduces the risk of presentation with potentially life-threatening adrenal failure. As in our case, features evolve over time and we recommend regular examinations for the development of associated features, which may benefit from symptomatic treatment.
. Three siblings with triple A syndrome with a novel frameshift mutation in the AAAS gene and a review of 17 independent patients with the frequent p.Ser263Pro mutation. Eur J Pediatr 2008;167:1049-55.