Endocrine Abstracts

Aim: Triple-A Syndrome (TAS) is a rare autosomal recessive disorder characterized by three cardinal symptoms: alacrimia, achalasia and adrenal insufficiency due to ACTH insensitivity. The disease is caused by mutation in the AAAS gene on chromosome 12q13. Mutations in AAAS were identified in more than 90% of individuals and families with TAS. The aim of this study is to discuss the clinical, laboratory and molecular genetic analysis results of 5 patients with TAS.

Materials and Methods: Five triple A syndrome patients from the same family who were genetically diagnosed were included in our study. Clinical, laboratory and genetic findings of the patients between 2018-2022 were obtained retrospectively.

Results: All of the patients were Syrians and relatives, 3 of them were siblings from the same family and 2 of them were cousins. The first admission of all patients was with achalasia findings. Esophagosgastromyotomy (dor funduplication) was performed in three patients and esophageal balloon dilatation was performed in 2 patients due to dysphagia. The first diagnosis of triple A syndrome(TAS) was made when she applied to the emergency room with dysphagia, nausea and vomiting and was examined in the intensive care unit, while achalasia was diagnosed and the diagnosis was made when she entered adrenal crisis in the follow-up. Then, people with similar symptoms in the family were examined and a total of 5 patients were diagnosed with TAS. All patients had alacrima, adrenal insufficiency and achalasia diagnoses. In addition, 2 had hyperreflexia, 4 had learning difficulties, 4 had hypernasal speech, 3 had muscle weakness, 3 had delayed speech, 2 had excessive sweating, 3 had thenar/hypothenar atrophy, and 3 had short stature. In all patients, AAAS gene was sequenced with sanger sequencing and c.1432C>T (p.Arg478*) mutation was detected in both alleles (homozygous).

Conclusion: Diagnosis of adrenal insufficiency is of vital importance in both the diagnostic and therapeutic stages of achalasia while examining and treating achalasia. Although these two diseases seem to be two different entities, the fact that they were detected in one patient at the same time is important in terms of recognizing and treating the neurological and other findings of triple A syndrome, especially alacrima. At the same time, it increases the incidence of genetic diseases in societies where consanguineous marriages are common. Therefore, the prevalence of consanguineous marriages in some regions of Syria and Turkey, diagnosis and treatment of genetic diseases are of particular importance.