title: Adult or late-onset triple A syndrome: case report and literature review.
abstract: Triple A syndrome is caused by mutations in the gene encoding ALADIN, leading to achalasia, alacrima and addisonism. Neurologic manifestations of the disease include motor neuron disease-like presentations, motor-sensory or autonomic neuropathy, optic atrophy, cerebellar ataxia, Parkinsonism, and mild dementia. We report a 60-year-old Japanese man with triple A syndrome. He was born to non-consanguineous parents. He underwent a surgical operation for achalasia at age 40, and thereafter, he developed a slowly progressive gait disturbance. Neurological examinations at age 60 revealed limb muscle wasting and weakness with pyramidal tract signs, distal-dominant sensory disturbance, optic atrophy, and autonomic dysfunction. Alacrima was detected using Schirmer test. All of these features were consistent with typical triple A syndrome. He lacked adrenal insufficiency that is frequently observed in patients with the classic phenotype of triple A syndrome. His sural nerve biopsy showed a moderate loss of myelinated fibers and hypomyelination. He was homozygous for a missense mutation, p.R155H, in the disease-causing gene, AAAS. Seven patients with genetically-confirmed, adult or late-onset triple A syndrome, including ours, have been reported to date. All the patients showed upper and lower motor neuron signs (100%), while sensory disturbance (29%) and autonomic dysfunction (57%) were less frequent. Careful assessment for alacrima followed by molecular genetic analysis of AAAS should be considered in patients who show a combined phenotype of motor neuron disease and sensory/autonomic disturbance, even in elderly patients.
authors.affiliation: Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Nakamura
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Yoshida
authors.forename: Tsuneaki
authors.initials: T
authors.lastname: Yoshinaga
authors.forename: Minori
authors.initials: M
authors.lastname: Kodaira
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shimojima
authors.forename: Yo-Ichi
authors.initials: Y
authors.lastname: Takei
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Morita
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Kayanuma
authors.forename: Shu-Ichi
authors.initials: S
authors.lastname: Ikeda
mesh_terms: D000309:Adrenal Insufficiency / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D004252:DNA Mutational Analysis / Q000379:methods; D004931:Esophageal Achalasia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology; D009431:Neural Conduction / Q000502:physiology; D009460:Neurologic Examination / Q000379:methods; D013497:Sural Nerve / Q000503:physiopathology; D014059:Tongue / Q000473:pathology