title: Nationwide survey of Alexander disease in Japan and proposed new guidelines for diagnosis.
abstract: Alexander disease (AxD) is a rare neurodegenerative disorder characterized by white matter degeneration and formation of cytoplasmic inclusions. Glial fibrillary acidic protein (GFAP) mutations have been reported in various forms of AxD since 2001. However, a definitive diagnosis remains difficult because of uncertain prevalence, and different clinical features seen in infantile AxD and adult AxD may lead to confusion and misdiagnosis. Here we report an epidemiological study conducted in Japan. Two nationwide questionnaire-based surveys were conducted using tentative diagnostic criteria. We gathered information regarding prevalence, neurological findings, magnetic resonance imaging (MRI) findings, electrophysiological findings, genetic information, and the results of therapeutic interventions and home care. Prevalence of various forms of AxD was determined as 27.3% (infantile), 24.2% (juvenile), and 48.5% (adult). Prevalence of AxD in Japan was estimated to be approximately 1 case per 2.7 million individuals. The main characteristics of infantile and juvenile AxD include delayed psychomotor development or mental retardation, convulsions, macrocephaly, and predominant cerebral white matter abnormalities in the frontal lobe on brain MRI. The main characteristics of adult AxD include bulbar signs, muscle weakness with hyperreflexia, and signal abnormalities and/or atrophy of medulla oblongata and cervical spinal cord on MRI. To ensure correct diagnosis of AxD, the physician should understand the importance of the process of GFAP genetic testing, which provides definitive diagnosis. Therefore, we propose new clinical guidelines for diagnosing AxD based on simplified classifications: cerebral AxD (type 1), bulbospinal AxD (type 2), and intermediate form (type 3).
authors.affiliation: Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi Hirokoji, Kajii-chou 465, Kamigyo-ku, Kyoto 602-0841, Japan. toyoshid@koto.kpu-m.ac.jp
authors.forename: Tomokatsu
authors.initials: T
authors.lastname: Yoshida
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sasaki
authors.forename: Mari
authors.initials: M
authors.lastname: Yoshida
authors.forename: Michito
authors.initials: M
authors.lastname: Namekawa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Seiichi
authors.initials: S
authors.lastname: Tsujino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sasayama
authors.forename: Ikuko
authors.initials: I
authors.lastname: Mizuta
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakagawa
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D038261:Alexander Disease / Q000175:diagnosis* / Q000453:epidemiology* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D006801:Humans; D007223:Infant; D007564:Japan / Q000453:epidemiology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D055815:Young Adult
chemical_list: D005904:Glial Fibrillary Acidic Protein