title: Triple-A syndrome with prominent ophthalmic features and a novel mutation in the AAAS gene: a case report.
abstract: BACKGROUND
  Triple-A syndrome (Allgrove syndrome) is an autosomal recessive disorder characterized by adrenal insufficiency, alacrima, achalasia, and - occasionally - autonomic instability. Mutations have been found in the AAAS gene on 12q13.
  
  
  METHODS
  We present the case of a 12 year-old boy with classic systemic features of triple-A syndrome and several prominent ophthalmic features, including: accommodative spasm, dry eye, superficial punctate keratopathy, and pupillary hypersensitivity to dilute pilocarpine. MRI showed small lacrimal glands bilaterally. DNA sequencing of PCR-amplified fragments from the 16 exons of the AAAS gene revealed compound heterozygosity for a new, out-of-frame 5-bp deletion in exon 15, c1368-1372delGCTCA, and a previously-described nonsense mutation in exon 9, c938C>T, R286X.
  
  
  CONCLUSIONS
  In addition to known ophthalmic manifestations, triple-A syndrome can present with accommodative dysregulation and ocular signs of autonomic dysfunction.
authors.affiliation: National Human Genome Research Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA. brooksb@mail.nih.gov
authors.forename: Brian P
authors.initials: BP
authors.lastname: Brooks
authors.forename: Robert
authors.initials: R
authors.lastname: Kleta
authors.forename: Rafael C
authors.initials: RC
authors.lastname: Caruso
authors.forename: Caroline
authors.initials: C
authors.lastname: Stuart
authors.forename: Jonathan
authors.initials: J
authors.lastname: Ludlow
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
mesh_terms: D000065:Accommodation, Ocular; D000309:Adrenal Insufficiency / Q000175:diagnosis / Q000235:genetics*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D001342:Autonomic Nervous System Diseases / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D015352:Dry Eye Syndromes / Q000175:diagnosis / Q000235:genetics*; D004931:Esophageal Achalasia / Q000175:diagnosis / Q000235:genetics*; D004948:Esotropia / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins; D028861:Nuclear Pore Complex Proteins; D015835:Ocular Motility Disorders / Q000175:diagnosis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*; D011681:Pupil Disorders / Q000175:diagnosis / Q000235:genetics; D013577:Syndrome
chemical_list: C416506:AAAS protein, human; D009419:Nerve Tissue Proteins; D028861:Nuclear Pore Complex Proteins; D011506:Proteins; D000324:Adrenocorticotropic Hormone