title: Triple A syndrome: a novel compound heterozygous mutation in the AAAS gene in an Italian patient without adrenal insufficiency.
abstract: Allgrove syndrome (or triple A syndrome) is a rare autosomal recessive disorder characterized by alacrima, achalasia, ACTH-resistant adrenal insufficiency and autonomic/neurological abnormalities. It is caused by mutations in the AAAS gene, located on chromosome 12q13. We describe a 42-year-old patient who presented with neuropathy and was found to have alacrima, achalasia, mild autonomic dysfunction with significant central and peripheral nervous system involvement. She was later diagnosed with oligosymptomatic triple A syndrome. Sequencing of the AAAS gene identified two heterozygous mutations within exon 14 and its donor splice site (p.L430F-c.1288C>T and c.1331+1G>T), one of which is novel. Allgrove syndrome should be suspected in patients with neurological impairment associated with two or more of the main symptoms (alacrima, achalasia or adrenal insufficiency).
authors.affiliation: Institute of Neurology, Catholic University of the Sacred Heart, Rome, Italy. mluigetti@gmail.com
authors.forename: M
authors.initials: M
authors.lastname: Luigetti
authors.forename: A
authors.initials: A
authors.lastname: Pizzuti
authors.forename: S
authors.initials: S
authors.lastname: Bartoletti
authors.forename: H
authors.initials: H
authors.lastname: Houlden
authors.forename: C
authors.initials: C
authors.lastname: Pirro
authors.forename: I
authors.initials: I
authors.lastname: Bottillo
authors.forename: F
authors.initials: F
authors.lastname: Madia
authors.forename: A
authors.initials: A
authors.lastname: Conte
authors.forename: P A
authors.initials: PA
authors.lastname: Tonali
authors.forename: M
authors.initials: M
authors.lastname: Sabatelli
mesh_terms: D000309:Adrenal Insufficiency / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D001342:Autonomic Nervous System Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D004252:DNA Mutational Analysis; D004931:Esophageal Achalasia / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007558:Italy; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D010523:Peripheral Nervous System Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D022821:RNA Splice Sites / Q000235:genetics; D013577:Syndrome
chemical_list: C416506:AAAS protein, human; D009419:Nerve Tissue Proteins; D028861:Nuclear Pore Complex Proteins; D022821:RNA Splice Sites