Abstract
Triple A syndrome is an autosomal recessive disorder characterized by alacrima, achalasia, ACTH-resistant adrenal insufficiency, autonomic dysfunction, and neurodegeneration. Mutations in the AAAS gene on chromosome 12q13 encoding the nuclear pore protein ALADIN have been reported in these patients. Over the period 1977–2008 we evaluated ten subjects with the clinical diagnosis of triple A syndrome. Molecular analysis was performed in seven patients and revealed that all except one are compound heterozygotes for two mutations in the AAAS gene. Two novel mutations were detected: c.123+2T>C resulted in splice defect while c.1261_1262insG mutation resulted in a truncated protein (p.V421fs), which most probably is not functional. Genotype–phenotype correlation could not be established. In all our patients, except one sibling of previously diagnosed brother and sister, genetic analysis was performed when at least two symptoms were present, usually alacrima and achalasia. Based on our experience, we recommend that in case of the presence of alacrima and at least one more symptom of triple A syndrome, adrenal function testing and molecular analysis should be performed. In all children with mutation in AAAS gene, regular follow up of adrenal function is necessary to avoid adrenal crisis and start substitution therapy as soon as adrenal insufficiency is noted.
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Acknowledgment
This work was supported by a grant of the Deutsche Forschungsgemeinschaft (DFG, HU395/3-5) to AH.
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The authors declare that they have no conflict of interest.
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Milenkovic, T., Zdravkovic, D., Savic, N. et al. Triple A syndrome: 32 years experience of a single centre (1977–2008). Eur J Pediatr 169, 1323–1328 (2010). https://doi.org/10.1007/s00431-010-1222-7
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DOI: https://doi.org/10.1007/s00431-010-1222-7