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. What is known: • Triple A syndrome is characterised 
by achalasia, alacrima, adrenal insufficiency, neurological impairment, and 
dermatological abnormalities. • A precise genotype-phenotype correlation has 
proved impossible to establish. What is new: • These cases add to a large number 
of similar case reports with limited novel information. • The newly identified 
AAAS gene mutation was reported.