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C. Villanueva-Mendoza, D. Rivera, J. C. Zenteno; Allgrove or Triple A Syndrome. A Case Report With Ophthalmic Abnormalities and Genetic Characterization. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3117.
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Triple A or Allgrove syndrome is a rare disease characterized by achalasia, alacrima, adrenocorticotrophic hormone (ACTH) resistant adrenal failure and some neurologic abnormalities. The inheritance is autosomal recessive and the diagnosis may be difficult because the patients may have only two of these principal symptoms.The Triple A gene was identified by Tullio-Pullet et al and codes for a protein called ALADIN. The gene localizes at 12q13. There is significant heterogeneity in the clinical features and the types of mutation reported in families with suspected triple A syndrome. We present the case of a seven year-old Mexican boy with history of achalasia and ophthalmic features consistent with alacrima and optic atrophy who carries a novel mutation in the triple A or ALADIN gene. Until now he has not had adrenal insufficiency.
Methods included complete systemic and ophthalmologic examination for phenotypic characterization of the patient.Genomic DNA from the patient and his unaffected parents was extracted from blood leukocytes following standard procedures. PCR amplification of the complete coding sequence (16 exons) as well as the exon-intron junctions of AAAS was performed in DNA from each participating subject, using specific primers derived from the published sequence of the gene. All samples were run in a 310 Genetic Analyzer.
The patient is a seven year old male, he was the second pregnancy of a consanguineous couple. He presented for deficient tear production since birth and also had a history of achalasia. Ophthalmic evaluation revealed: reduced tear production; inferior superficial punctate keratopathy and bilateral optic atrophy.Repeated adrenal function tests have shown normal results. AAAS gene analysis demonstrated a homozygous A to G mutation at nucleotide position 122 in exon 1 in DNA from the patient. This change predicts the replacement of glutamine (CAG) to arginine (CGG), at residue position 41 of Aladin protein and was designated Q41R. Nucleotidic analysis in DNA from the parents disclosed that both of them were heterozygous for this mutation.
The novel Q41R mutation described in this patient confirms the molecular diagnosis of Triple A syndrome and indicates the importance of the molecular analysis for the final diagnosis. Ophthalmologists and other clinicians should consider this condition even in the absence of some of the cardinal features.
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