Absence of Tears as a Key Clinical Clue to Triple A Syndrome: A Case Report

Abstract

Background: Triple A syndrome (TAS), also referred to as Allgrove Syndrome (AS), is a rare inherited multisystem disorder. Mutations in the AAAS gene, which encodes the nuclear pore complex protein ALADIN, are responsible for this syndrome, named for its main features of (ALacrima, Achalasia, ADrenal Insufficiency, and Neurological disorder). Absence of tears (alacrima), the earliest clinical manifestation of this syndrome, is frequently overlooked, leading to significant delays in clinical recognition. Case Report: We report a young female child who presented late with features suggestive of severe adrenal crisis secondary to primary adrenal insufficiency (PAI). She was born to first-degree relatives who had three deceased siblings with similar presentations, all of whom presumably died from untreated adrenal crises. Alacrima had been present in all siblings since birth and served as the key diagnostic clue in this case, enabling early recognition and appropriate life-saving intervention. The clinical presentation of TAS is highly heterogeneous, and early signs are nonspecific, which often contributes to diagnostic uncertainty and delays or missed diagnoses. In a country with limited resources for specific testing and inaccessible genetic diagnosis, such as Sudan, diagnosis relies primarily on careful clinical evaluation to identify key phenotypic features that eventually lead to accurate and timely diagnosis and management. Conclusion: This case report underscores the importance of clinical awareness in the identification and timely management of TAS. It also highlights the critical role of careful clinical evaluation, particularly in children presenting with absence of tears, hyperpigmentation, and recurrent hypoglycemia, to facilitate early identification of cases and prevent life-threatening outcomes.