Triple A syndrome: Non-sense c.884G>A mutation making sense through its clinical triad
Year: 2025
Type: article
Study design: Case Report
Abstract: Triple A syndrome is a rare autosomal recessive disorder characterized by triad of achalasia, alacrimia, and adrenal insufficiency. Autonomic dysfunction, neurological, and dermatological manifestations widen phenotypic spectrum. It arises from mutations in AAAS gene. Symptoms typically manifest in childhood; delayed presentations into adulthood are exceedingly rare. We report a 25-year-old male with 17-year history of progressive dysphagia, alacrimia, generalized fatigue, and diffuse hyperpigmentation. Laboratory evaluation and imaging suggested primary adrenal insufficiency. Esophageal manometry demonstrated achalasia. Ophthalmological assessment confirmed severe dry eye disease. Genetic testing identified a pathogenic homozygous non-sense mutation in AAAS gene (c.884G>A). Treatment with glucocorticoid and mineralocorticoid replacement, artificial tears, and esophageal pneumatic dilation led to significant clinical improvement. This case underscores presentation with classical triad of the syndrome at 8-years of age, albeit delayed first physician contact and diagnosis. Early recognition of its cardinal features is critical to prevent life-threatening complications such as adrenal crises and esophageal perforation.
Authors: Anurag Roy, Soumyadeep Datta, Vatsal Jayantbhai Sojitra, Yogesh Chandra Porwal
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4408068424