Triple-A Syndrome: A Rare Etiology of Adult Achalasia

Abstract

Achalasia is the best-described primary motor disorder of the esophagus. Its association with alacrima and adrenocorticotropin hormone (ACTH)-resistant adrenal insufficiency has been described in childhood. This triple-A syndrome is an autonomic recessive disorder first described by Allgrove in 1978 (1). Variable and progressive neurological impairment involves the central, peripheral, and autonomic nervous systems. Therefore, some authors called this syndrome the 4A syndrome because of an association with signs of autonomic dysfunction such as postural hypotension, impaired cardiovascular reflexes, or unequal pupils (2). Dermatological features such as palmoplantar hyperkeratosis but also facial dimorphism and osteoporosis may be observed in affected patients (3). In some patients, a characteristic hypernasal speech due to an incomplete velopharyngeal closure has been reported (3). Mutations of the achalasia–addisonianism–alacrima syndrome (AAAS) gene has been identified in families with the triple-A syndrome (4, 5). This gene encodes a protein that belongs to the tryptophan–aspartate (WD)-repeat family of regulatory proteins and localizes to nuclear pore complexes (NPCs) (6). When mutated, this protein fails to localize to NPCs and remains in the cytoplasm. A recent study suggested the possibility of diagnosing triple-A syndrome in adults as shown by the 20% prevalence of alacrima in 20 adults with achalasia (7). We report here the first case of incomplete triple-A syndrome