OBJECTIVE: Triple-A or Allgrove syndrome is an autosomal recessive disorder due 
to mutations in the AAAS gene, which encodes a nucleoporin named ALADIN. It is 
characterized by a classical clinical triad: alacrima, achalasia and adrenal 
insufficiency, the canonic symptoms that are associated with progressive 
peripheral neuropathy. Only a few cohorts have been reported. The objective of 
the present study was to characterize the various spectra of adrenal function in 
Triple-A patients.
METHODS: A retrospective clinical and biological monitoring of 14 patients (10 
families) was done in a single multidisciplinary French center. All had AAAS 
gene sequenced and adrenal function evaluation.
RESULTS: Nine different AAAS mutations were found, including one new mutation: 
c.755G>C, p.(Trp252Ser). Regarding adrenal function, defects of the zona 
fasciculata and reticularis were demonstrated by increased basal ACTH levels and 
low DHEAS levels in all cases regardless of the degree of glucocorticoid 
deficiency. In contrast, mineralocorticoid function was always conserved: i.e., 
normal plasma renin level associated with normal aldosterone level. The main 
prognostic feature was exacerbation of neuropathy and cognitive disorders.
CONCLUSIONS: These data suggest that, in Triple-A patients, adrenal function can 
be deficient, insufficient or compensated. In our cohort after the first decade 
of life, there does not appear to be any degradation of adrenal function over 
time. However, patients with compensated adrenal function should be informed and 
educated to manage a glucocorticoid replacement therapy in case of stressful 
conditions, with no need for systematic long-term treatment.