title: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia linked CSF1R mutation: Report of four Korean cases.
abstract: We describe detailed clinical, biochemical, neuroimaging and neuropathological features in adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), encompassing hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD), linked to colony-stimulating factor 1 receptor (CSF1R) mutations in four Korean cases. Clinical, biochemical, neuroimaging and neuropathological findings were obtained by direct evaluation and from previous medical records. The genetic analysis of the CSF1R gene was done in two autopsy-confirmed ALSP cases and two cases where ALSP was suspected based on the clinical and neuroimaging characteristics. We identified two known mutations: c.2342C>T (p.A781V) in one autopsy-proven HDLS and clinically ALSP-suspected case and c.2345G>A (p.R782H) in another autopsy-proven POLD case. We also found a novel mutation (c.2296A>G; p.M766V) in a patient presenting with hand tremor, stuttering and hesitant speech, and abnormal behavior whose father died from a possible diagnosis of spinocerebellar ataxia. To the best of our knowledge, this is the first documented ALSP-linked CSF1R mutation in Korea and supports the suggestion that HDLS and POLD, with pathological characteristics that are somewhat different but which are caused by CSF1R mutations, are the same spectrum of disease, ALSP.
authors.affiliation: Department of Neurology, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Busan, South Korea.
authors.forename: Eun-Joo
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Department of Neurology, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, South Korea.
authors.forename: Jin-Hong
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Department of Pathology, Pusan National University Yangsan Hospital, Yangsan, South Korea.
authors.forename: Jeong Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Neurology, Ilsan Hospital, National Health Insurance Corporation, Goyang-shi, South Korea.
authors.forename: Jong Hun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Duk L
authors.initials: DL
authors.lastname: Na
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Yeon-Lim
authors.initials: YL
authors.lastname: Suh
authors.affiliation: Department of Neurology, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, South Korea.
authors.forename: Sun Jae
authors.initials: SJ
authors.lastname: Hwang
authors.affiliation: Department of Neurology, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, South Korea.
authors.forename: Jae-Hyeok
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Psychiatry, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Busan, South Korea.
authors.forename: Young Min
authors.initials: YM
authors.lastname: Lee
authors.affiliation: Department of Rehabilitation medicine, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Busan, South Korea.
authors.forename: Myung-Jun
authors.initials: MJ
authors.lastname: Shin
authors.affiliation: Department of Neurology, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Busan, South Korea.
authors.forename: Myung Jun
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Busan, South Korea.
authors.forename: Seong-Jang
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, Catholic University of Daegu, Gyeongsan, South Korea.
authors.forename: Uicheul
authors.initials: U
authors.lastname: Yoon
authors.affiliation: Department of Pathology, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Busan, South Korea.
authors.forename: Do Youn
authors.initials: DY
authors.lastname: Park
authors.affiliation: Department of Neurology, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Busan, South Korea.
authors.forename: Dae Soo
authors.initials: DS
authors.lastname: Jung
authors.affiliation: Department of Pathology, Pusan National University Yangsan Hospital, Yangsan, South Korea.
authors.forename: Jae Woo
authors.initials: JW
authors.lastname: Ahn
authors.affiliation: Department of Anatomy, Pusan National University School of Medicine and Medical Research Institute, Busan, South Korea.
authors.forename: Suk
authors.initials: S
authors.lastname: Sung
authors.affiliation: Department of Forensic Medicine, Pusan National University School of Medicine and Medical Research Institute, South Korea. Electronic address: gyhuh@pusan.ac.kr.
authors.forename: Gi Yeong
authors.initials: GY
authors.lastname: Huh
mesh_terms: D000328:Adult; D017668:Age of Onset; D044466:Asian People; D001369:Axons / Q000473:pathology*; D001921:Brain / Q000473:pathology; D005260:Female; D006801:Humans; D056784:Leukoencephalopathies / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009154:Mutation; D009457:Neuroglia / Q000473:pathology*; D059906:Neuroimaging / Q000379:methods; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics*; D014202:Tremor / Q000209:etiology / Q000235:genetics*
chemical_list: D016186:Receptor, Macrophage Colony-Stimulating Factor
keywords: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP); CSF1R; Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS); Leukoencephalopathy; Pigmentary orthochromatic leukodystrophy (POLD); Young onset dementia