[7] Individuals affected by AAA have adrenal insufficiency/Addison's disease due to ACTH resistance, alacrima (absence of tear secretion), and achalasia (a failure of a ring of muscle fibers in the lower part of the esophagus to relax) called the lower esophageal sphincter at the cardia (very upper portion of the stomach).

[9] Triple-A syndrome is associated with mutations in the AAAS gene which encodes a protein known as ALADIN (ALacrima Achalasia adrenal Insufficiency Neurologic disorder).

[10][11][12] In 2000, Huebner et al. mapped the syndrome to a 6 cM interval on human chromosome 12q13 near the type II keratin gene cluster.

[4] Furthermore, genotypic heterogeneity has also been documented suggesting that there may be other genes involved in this genetic disorder as well as unknown environmental factors that result in the phenotypic expression of the disease.

[7] ALADIN protein is a component of the nuclear pore complex, situated toward its cytoplasmic side.

Mutant ALADIN remains mis-localized in the cytoplasm[14] and causes selective failure of nuclear protein import and hypersensitivity to oxidative stress.

Clinical signs may lead to the diagnosis such as the lack of tears and digestive issues, such as acid reflux disease in infancy as well as symptoms of adrenal insufficiency such as frequent bouts of low blood sugars are highly suggestive of the disorder.

The gold standard for confirming achalasia is a 24 hours manometry of oesophagus.This is a test that measures the pressure inside the esophagus.

Achalasia can be treated with surgical intervention resulting in improved passage of food and drink into the stomach.