TRIPLE-A SYNDROME

A RARE PRESENTATION OF ADRENAL INSUFFICIENCY

Abstract

INTRODUCTION/BACKGROUND
Triple-A syndrome or Allgrove syndrome is a rare autosomal recessive congenital disorder. It is characterized by Addisonianism, achalasia and alacrima. It is a progressive disorder that can take years to develop the fullblown clinical picture.

CASE
We report 2 individuals with Triple-A syndrome who initially presented with recurrent hypoglycemic seizures at about 4 years old. They also had faltering growth with short stature. Both had significant hyperpigmentation, without ambiguous genitalia or neurological abnormality. Hormonal assay confirmed glucocorticoid deficiency, with sparing of mineralocorticoid involvement. Both were subsequently started on hydrocortisone replacement. In the subsequent years, both developed new symptoms of recurrent vomiting and dysphagia, suggesting achalasia. Subsequently, patient 2 had barium swallow study done which confirmed an esophageal dysmotility disorder. Retrospectively, both patients were also found to have absent tear production from a very young age, signifying alacrima. Patient 1 managed to undergo Whole Exome Sequencing (WES) study and a homozygous variant of uncertain significance (VUS) was identified in the AAAS gene (cDNA: NM_015665.6:c.1087G>A). In view this is the gene of interest that fits into the clinical picture, the mutation was likely pathological.

CONCLUSION
High index of suspicion is required to diagnose this rare entity. Unexplained cases of adrenal insufficiency should be carefully evaluated for signs and symptoms of alacrima and achalasia.