P-10 A rare case of Triple A Syndrome with familial involvement

Abstract

Abstract Introduction Alacrimia, achalasia cardia, and adrenocorticotrophic hormone (ACTH)-resistant adrenal insufficiency make up the triple-A syndrome. It is an uncommon disease with an autosomal recessive inheritance pattern. The AAAS gene, which codes for the ALADIN protein and is located on chromosome 12q13, is the cause of Allgrove syndrome. The initial and typical symptoms are achalasia cardia and adrenal insufficiency. The majority of neurological disorders have autonomic signs, and they typically show in later life. The other typical neurological conditions are polyneuropathy, amyotrophy, and optic atrophy. Clinical Case A 25-year-old female patient presented to our clinic with complaints of weakness, dizziness, and hyperpigmentation of the skin. Her medical history revealed a recent intensive care unit (ICU) stay due to hypotension, during which her condition was managed with steroid therapy. However, she did not continue the steroid treatment after discharge. Notably, the patient had a family history of achalasia with operative intervention in all three siblings. The patient and her family members were also under the care of a gastroenterology specialist. Additionally, the patient reported experiencing dry eyes, for which she was using artificial tears. Physical examination revealed hyperpigmentation of tongue, gums and buccal mucosa. Upon examination, her baseline investigations revealed a hemoglobin of 11.4 g/dL, sodium 137 mmol/L and potassium 4.0 mmol/L. The patient's adrenocorticotropic hormone (ACTH) level was measured at 1250 pg/ml, with a basal cortisol level of 0.5 ug/dL, leading to the diagnosis of adrenal insufficiency. Hydrocortisone treatment was initiated at a dosage of 2×10mg, resulting in a decline of the ACTH level to 31. Given the combination of symptoms including achalasia, alacrima, and adrenal insufficiency, genetic testing was conducted. Both alleles revealed a homozygous c.1432C>T (p.Arg478*) mutation, confirming the diagnosis of Triple A Syndrome. Following the genetic diagnosis, a familial investigation was initiated. This investigation revealed the presence of the homozygous positive mutation in two siblings and two cousins. The constellation of symptoms and the genetic findings confirmed the occurrence of Triple A Syndrome within this family. Conclusion This case highlights the significance of recognizing Triple A Syndrome as an underlying cause of adrenal insufficiency in the presence of achalasia, alacrima, and a suggestive clinical history. In order to confirm the diagnosis and identify any affected family members, genetic testing is crucial. To avoid potential complications brought on by adrenal insufficiency and other systemic Triple A Syndrome manifestations, early identification and treatment are crucial.