Clinical and genetic characterisation of a series of patients with triple A syndrome

Erdal Kurnaz, Paolo Duminuco, Zehra Aycan, Şenay Savaş-Erdeve, Nursel Muratoğlu Şahin, Melişah Keskin, Elvan Bayramoğlu, Marco Bonomi, Semra Çetinkaya

Research output: Contribution to journalArticlepeer-review

Abstract

Triple A syndrome (TAS) or Allgrove syndrome (OMIM #231550) is a rare autosomal recessive disorder characterised by adrenocorticotropic hormone-resistant adrenal insufficiency, alacrima, achalasia, and neurological and dermatological abnormalities. Mutations in the AAAS gene on chromosome 12q13 encoding the nuclear pore protein ALADIN have been reported in these patients. Between 2006 and 2017, we evaluated six patients with a clinical diagnosis of TAS, based on the presence of at least two symptoms, usually adrenal insufficiency and alacrima. In all cases, genetic analysis revealed homozygous mutations in the AAAS gene. One novel mutation was detected: a homozygous 10-bp deletion (c.1264_1273del, p.Q422NfsX126) in exon 14 of the AAAS gene that caused a frameshift that introduced an aberrant stop codon after 126 amino acids. This genetic variant is likely to be pathogenic because it caused a significant change in protein structure. A precise genotype–phenotype correlation was impossible to establish. Conclusions: Based on our experience, we recommend that molecular analysis should be performed in the presence of alacrima and at least one more symptom of TAS. Our cases share many clinical features of TAS and underline the variability in this syndrome, as well as the need for thorough investigation following a multidisciplinary approach.(Table presented.)

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalEuropean Journal of Pediatrics
DOIs
Publication statusPublished - Mar 2018

Keywords

  • AAAS gene
  • ACTH resistance
  • Adrenal insufficiency
  • Triple A syndrome

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Fingerprint Dive into the research topics of 'Clinical and genetic characterisation of a series of patients with triple A syndrome'. Together they form a unique fingerprint.

Cite this