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Triple A syndrome
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

Triple A syndrome

Triple A syndrome, also known as Allgrove syndrome, is a rare inherited condition characterized by three hallmark features: achalasia, adrenal insufficiency, and alacrima.

Overview

Triple A syndrome (or Allgrove syndrome) is a progressive genetic disorder. Most affected individuals present with three specific features: achalasia, adrenal insufficiency, and alacrima, though some individuals may only exhibit two of these characteristics. The symptoms typically develop gradually over several years and can vary significantly in severity, even among members of the same family.

Symptoms & Features

The features of Triple A syndrome can affect multiple systems of the body, including the digestive, endocrine, and nervous systems:

Hallmark Features

  • Achalasia: A movement disorder of the esophagus (the tube connecting the throat to the stomach) that causes severe feeding difficulties, vomiting, and weight loss. Symptoms typically appear between infancy (6 months) and late adolescence.
  • Adrenal insufficiency: Occurs when the adrenal glands do not produce enough hormones, leading to fatigue, loss of appetite, weight loss, low blood pressure, low blood glucose (hypoglycemia), and seizures.
  • Alacrima: A reduced or complete absence of tear secretion, which is often the earliest noticeable sign of the condition in infants.

Neurological and Autonomic Features

Approximately one-third of individuals with Triple A syndrome experience dysfunction of the autonomic nervous system (dysautonomia), which regulates involuntary body processes. Symptoms include:

  • Abnormal sweating
  • Changes in saliva production
  • Difficulty regulating blood pressure and heart rate
  • Unequal pupil size (anisocoria)
  • Gradual decline in cognitive abilities
  • Muscle weakness and difficulty coordinating movements (ataxia)
  • Speech problems (dysarthria)
  • Optic atrophy (degeneration of the optic nerves)

Other Physical Features

  • Short stature and a small head size (microcephaly)
  • Brittle bones prone to fracture (osteoporosis) in adulthood
  • Skin abnormalities, including darkening of the skin and thickening of the skin on the palms and soles (hyperkeratosis)

Frequency

Triple A syndrome is a rare condition, estimated to affect approximately 1 in 1 million individuals. However, due to underdiagnosis, the actual prevalence may be higher.

Causes

Triple A syndrome is primarily caused by variants (mutations) in the AAAS gene, which provides instructions for making a protein called ALADIN. This protein is highly active in the cells of the brain, adrenal glands, and digestive system. ALADIN is located in the nuclear envelope, where it helps regulate the movement of molecules into and out of the cell nucleus.

Variants in the AAAS gene lead to the production of an abnormal, non-functional version of the ALADIN protein. This disruption impairs the communication and transport of molecules between the nucleus and the rest of the cell, affecting cellular growth, maturation, and repair. The exact mechanism linking these cellular changes to the specific symptoms of Triple A syndrome is still being studied.

Some individuals with Triple A syndrome do not have mutations in the AAAS gene. In rare cases, mutations in other genes, such as GMPPA and TRAPPC11, have been associated with similar symptoms.

Inheritance

This condition is inherited in an autosomal recessive pattern. This means that an individual must inherit two mutated copies of the gene (one from each parent) to develop the disorder. Parents of an affected individual typically carry one copy of the mutated gene but do not show signs or symptoms of the condition.

Other Names for This Condition

  • 2A syndrome
  • 3A syndrome
  • 4A syndrome
  • AAA
  • AAA syndrome
  • Achalasia-addisonianism-alacrima syndrome
  • Achalasia-alacrima syndrome
  • Adrenal insufficiency-achalasia-alacrima syndrome
  • Allgrove syndrome
  • Double A syndrome
  • Quarternary A syndrome

Frequently Asked Questions

Rapid onset of severe weakness, dizziness, low blood pressure (feeling faint or actually fainting), intense abdominal pain, vomiting, low blood sugar (confusion or seizures), and a sudden change in skin color (pale or mottled) are red‑flag signs. If any of these appear, treat as an adrenal emergency: give injectable hydrocortisone and call emergency services immediately.
Look for progressive trouble swallowing solid foods, frequent vomiting of undigested food, weight loss despite adequate intake, and a sensation of food getting “stuck” in the chest. A barium swallow study or esophageal manometry performed by a pediatric gastroenterologist can confirm the lack of normal esophageal peristalsis and a tight lower esophageal sphincter, which are hallmarks of achalasia.
Keep a symptom diary noting triggers (heat, stress, meals) and the severity of sweating or dizziness. Encourage a balanced fluid and salt intake (unless contraindicated by hypertension), wear breathable clothing, and avoid extreme temperatures. For blood‑pressure instability, a low‑dose fludrocortisone or midodrine may be prescribed by an endocrinologist; always discuss medication adjustments with your care team.
Because tear production is reduced, the eyes can become dry, irritated, and prone to corneal abrasions. Use preservative‑free artificial tears every 2–4 hours during the day, lubricating ointment at bedtime, and consider a moisture‑retaining eye mask at night. Regular ophthalmology visits are essential to monitor corneal health and to prescribe protective glasses or bandage lenses if needed.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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