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: Katsuya Nakamura, Kunihiro Yoshida, Tsuneaki Yoshinaga, Minori Kodaira, Yasuhiro Shimojima, Yo-Ichi Takei, Hiroshi Morita, Katsuhiko Kayanuma, Shu-Ichi Ikeda
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 297 Issue 1-2 Pg. 85-8 (Oct 15 2010) ISSN: 1878-5883 [Electronic] Netherlands
• PMID: 20674935 (Publication Type: Case Reports, Journal Article, Review)
• Copyright: Copyright 2010 Elsevier B.V. All rights reserved.

Topics

• Adrenal Insufficiency (genetics, pathology, physiopathology)
• DNA Mutational Analysis (methods)
• Esophageal Achalasia (genetics, pathology, physiopathology)
• Humans
• Male
• Middle Aged
• Muscle, Skeletal (pathology)
• Neural Conduction (physiology)
• Neurologic Examination (methods)
• Sural Nerve (physiopathology)
• Tongue (pathology)