Triple A syndrome

Triple A syndrome, also known as Allgrove syndrome or AAA syndrome (achalasia-addisonianism-alacrima syndrome), is a rare autosomal recessive multisystem disorder characterized by three cardinal features: adrenal insufficiency (Addison disease), achalasia of the esophageal cardia, and alacrima (absence or deficiency of tear production). The condition is caused by mutations in the AAAS gene on chromosome 12q13, which encodes a protein called ALADIN (alacrima-achalasia-adrenal insufficiency neurologic disorder), a component of the nuclear pore complex. The disease typically presents in childhood, though the three main features may not all appear simultaneously and can develop over time. Alacrima is often the earliest manifestation, sometimes present from birth, while achalasia and adrenal insufficiency usually develop during the first decade of life. The syndrome affects multiple body systems beyond the classic triad. Neurological involvement is common and can be progressive, including autonomic neuropathy, peripheral sensorimotor neuropathy, cerebellar ataxia, optic atrophy, intellectual disability, and bulbospinal amyotrophy. Skin changes such as hyperkeratosis of the palms and soles may also occur. The adrenal insufficiency primarily involves glucocorticoid deficiency, though mineralocorticoid deficiency can also develop. Achalasia leads to difficulty swallowing, regurgitation, and aspiration risk. Treatment is symptomatic and supportive. Adrenal insufficiency requires lifelong glucocorticoid replacement therapy, and mineralocorticoid supplementation may be needed. Achalasia is managed with surgical or endoscopic interventions such as Heller myotomy or balloon dilation. Alacrima is treated with artificial tears to prevent corneal damage. Neurological complications are managed supportively. Early diagnosis and appropriate hormone replacement are critical, as unrecognized adrenal insufficiency can be life-threatening. Regular monitoring by a multidisciplinary team including endocrinologists, gastroenterologists, neurologists, and ophthalmologists is recommended.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Triple A syndrome