Triple A syndrome (Allgrove syndrome) – A journey from clinical symptoms to a syndrome

Abstract

Triple A syndrome (Allgrove syndrome) is characterized by a triad of specific features, namely, alacrimia, adrenal insufficiency, and achalasia cardia. It is a rare autosomal recessive disorder. In the present study, an 18-year-old boy was presented with complaints of decreased tears, darkening of the skin, difficulty in walking and standing up from sitting position, and difficulty in swallowing liquids. Adrenal insufficiency, alacrimia, achalasia, and neurological manifestations were confirmed with relevant laboratory investigations. His condition improved with steroids and artificial teardrops. However, a vigilant eye of the clinician for clinical clues of syndromic manifestation will help in early diagnosis and proper management.

Mineralocorticoid Deficiency as an Early Presenting Symptom of Allgrove Syndrome With Novel Mutation: A Case Report

“…AS is an autosomal recessive disorder, and has been linked with mutations in the AAAS (achalasiaaddisonianism-alacrimia syndrome) gene, localized on chromosome 12q13 that encodes for the ALADIN (Alacrimia-Achalasia-Adrenal Insufficiency and Neurologic disorder) protein. The presence of this mutation confirms the diagnosis of Allgrove syndrome [3].…”

“…Considering the widely phenotypic variability of the presentation, the initial diagnosis is often delayed. Hence, physicians should be vigilant with a high index of suspicion to bridge the significant gap between initial symptoms and the diagnosis [2,3]. As compared to others, our patient has an early age of presentation.…”

“…However, it has been found that ACTH has some neuropathic effect, and its receptor gene could provide some clue and clarify the association between the three pathognomonic features of this syndrome. There is no specific parenchymal finding in brain magnetic resonance imaging (MRI) mentioned in the literature, but it has revealed focal demyelination at the medulla and inferior cerebellar peduncle [3,5].…”

“…Diagnosis of Allgrove can be clinically suspected but confirmation must be done through presence of genetic mutation on chromosome 12q13, AAAS (achalasia-addisonianism-alacrima syndrome) gene that encodes for ALADIN (Alacrimia-Achlasia-Adrenal Insufficiency and Neurologic disorder) protein [3]. Not all patients with the AAAS gene mutation present with the characteristic triad of AS, as the triad may be incomplete.…”

Nuclear Envelope and Nuclear Pore Complexes in Neurodegenerative Diseases—New Perspectives for Therapeutic Interventions

“…AAA (triple A) is an autosomal recessive neuroendocrine disease in which esophagus achalasia, anhidrosis, and adrenocortical insufficiency are associated with muscular atrophy and weakness [ 90 ]. Adult triple A syndrome can have progressive neurodegeneration, Parkinson’s syndrome, and cognitive impairment [ 91 ]. ALADIN has been identified as the causative gene for triple A syndrome.…”