BACKGROUND: Triple A syndrome, also known as Allgrove syndrome, is a rare 
autosomal recessive disorder characterized by three cardinal symptoms: adrenal 
insufficiency due to ACTH insensitivity, achalasia and alacrima. Various 
progressive neurological abnormalities and skin changes have been described in 
association with the syndrome. The disease is caused by mutation in the AAAS 
gene on chromosome 12q13. AAAS encodes a protein named ALADIN which is part of 
the nuclear pore complex (NPC). The mislocalization of mutated ALADIN proteins 
in the cytoplasm and/or the nucleus results in an impaired protein function. 
Phenotypes of previously reported patients with triple A syndrome varied within 
and between affected families so that no genotype-phenotype could be 
established.
METHODS: Genetic analysis was performed in two unrelated patients, their parents 
and one sister. AAAS coding sequences including exon-intron boundaries were 
amplified and sequenced using an ABI 3100 sequencing machine.
PATIENTS: We present two unrelated Swiss patients with triple A syndrome 
demonstrating similar phenotypic characteristics. Both showed a progression of 
the disease presenting with adrenal insufficiency and alacrima in early 
childhood. At the age between 30-40 years they developed symptomatic achalasia. 
The pattern and severity of progressive neurological and autonomic dysfunction 
was comparable. In both patients molecular genetic analysis revealed an 
identical novel homozygous mutation (c.618delC, p.Ser207fs) in the AAAS gene.
CONCLUSION: Recent genotype/phenotype studies showed a marked inter- and 
intrafamiliar variability in triple A syndrome. Here we present a rather tight 
genotype/phenotype correlation in two unrelated patients carrying the identical 
novel p.Ser207fs mutation in the AAAS gene.