Novel homozygous AAAS p.Leu484Arg variant in Allgrove syndrome presenting as adrenal crisis with alacrima

ABSTRACT

Allgrove syndrome, also known as triple A (3A) syndrome, is a rare autosomal recessive multisystem disorder characterized by the classical triad of alacrima, achalasia, and adrenocorticotropin hormone-resistant adrenal insufficiency. The condition results from mutations in the AAAS gene (chromosome 12q13), which encodes the Alacrima-Achalasia-aD renal insufficiency neurologic disorder protein. While approximately 70% of patients present with the complete triad, the heterogeneous phenotype renders early diagnosis challenging as classical features may not all be present initially. Approximately one-third of patients develop autonomic dysfunction, warranting classification as 4A syndrome. Management requires a multidisciplinary team approach involving endocrinologists, neurologists, gastroenterologists, ophthalmologists, developmental specialists, dentists, geneticists, and surgeons. This case report describes a 4-year-old girl diagnosed with 3A syndrome presenting with seizures, hyperpigmentation, and reduced tear production.