Research Information System
JOURNAL OF ISTANBUL FACULTY OF MEDICINE-ISTANBUL TIP FAKULTESI DERGISI, vol.89, no.1, pp.63-69, 2026 (ESCI, Scopus, TRDizin)
Objective: Allgrove syndrome (Triple-A syndrome) is a rare autosomal recessive disorder characterized by alacrima, achalasia, and adrenal insufficiency, often accompanied by neurological and autonomic findings. Its clinical heterogeneity and rarity frequently delay diagnosis. The aim of our study is to emphasize the importance of a thorough physical examination and family history, as well as to raise awareness about the syndrome. Materials and Methods: We describe six patients from four unrelated families diagnosed with Allgrove syndrome in eastern T & uuml;rkiye. Detailed clinical evaluations and genetic analyses were conducted. Aladin WD Repeat Nucleoporin (AAAS) gene variants were identified using next-generation sequencing and Sanger sequencing. Results: All patients presented with alacrima and achalasia; adrenal insufficiency was absent in one patient. Neurological manifestations were noted in four patients. Homozygous AAAS variant c.1066_1067delCT (p.Leu356Valfs*8) was identified in five cases; one patient carried the c.1432C>T (p.Arg478*) variant. Consanguinity was present in three families. Despite the rarity of this syndrome, two patients were diagnosed by a family physician unfamiliar with the condition, based on careful anamnesis. Conclusion: This study adds to the growing literature on Allgrove syndrome by highlighting the high frequency of the c.1066_1067delCT variant, suggesting a founder effect in eastern T & uuml;rkiye. The phenotypic variability observed-even among siblings-supports previous findings of limited genotype-phenotype correlation. Our report highlights the critical diagnostic role of primary care physicians in rare disease detection. Our findings emphasize raising awareness of Allgrove syndrome and integrating regional variant data into diagnostic algorithms. Early recognition by non-specialists can significantly reduce diagnostic delays in multisystemic genetic disorders.