title: Late infantile metachromatic leukodystrophy: Clinical manifestations of five Taiwanese patients and Genetic features in Asia.
abstract: BACKGROUND
  This study was conducted to describe the clinical and genetic features of patients with late infantile metachromatic leukodystrophy.
  
  
  METHODS
  Clinical and genetic manifestations of five Taiwanese patients with late infantile metachromatic leukodystrophy from January 2003 to April 2014 were reviewed. The genetic features of such patients reported in Asian countries during a period of 20 years were also analyzed.
  
  
  RESULTS
  The median age at disease onset was 1 year and 3 months with the first clinical symptom being gait disturbance. All five patients became bed-ridden at a median age of 2 years and 5 months. Nerve conduction velocity revealed demyelinating polyneuropathy and brain MRI disclosed tigroid and leopard skin pattern of dysmyelination in all 5 patients. All patients had decreased ARSA activities in leukocytes accounting for 15.88% to 30.75% of controls. Five novel mutations, p.A316D, p.G303R, p.Q176X, p.R293X, and c.749 insGCGGGCCA, were identified in our case series. Eighteen patients, including our 5 patients, were reported in Asian countries. A total of 22 different disease-causing alleles were found, in which p.W320X was identified in Taiwan and China, and p.G101V was found in Taiwan and Korea.
  
  
  CONCLUSIONS
  Patients with late infantile metachromatic leukodystrophy exhibited a rapid and devastating clinical course. The pattern of dysmyelination on brain MRI together with peripheral demyelination polyneuropathy indicates that evaluation of ARSA activity in leukocytes is warranted. A wide diversity of ARSA gene mutations was noted in Asia.
authors.affiliation: Department of Pediatrics, Taichung Veterans General Hospital, 1650, Taiwan Boulevard Sec. 4, Taichung, 40705, Taiwan.
authors.forename: Hsiang-Ru
authors.initials: HR
authors.lastname: Liaw
authors.affiliation: Department of Pediatrics, Taichung Veterans General Hospital, 1650, Taiwan Boulevard Sec. 4, Taichung, 40705, Taiwan.|School of Medicine, Chung Shan Medical University, 110, Sec. 1, Jianguo N. Rd, Taichung, 40201, Taiwan.
authors.forename: Hsiu-Fen
authors.initials: HF
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Tungs' Taichung Metroharbor Hospital, 699, Taiwan Boulevard Sec. 8, Wuchi, Taichung, 435, Taiwan. chi-cs@hotmail.com.|School of Medicine, Chung Shan Medical University, 110, Sec. 1, Jianguo N. Rd, Taichung, 40201, Taiwan. chi-cs@hotmail.com.
authors.forename: Ching-Shiang
authors.initials: CS
authors.lastname: Chi
authors.affiliation: Department of Pediatrics, Taichung Veterans General Hospital, 1650, Taiwan Boulevard Sec. 4, Taichung, 40705, Taiwan.|Institute of Molecular Biology, National Chung Hsing University, 250, Kuo Kuang Rd, Taichung, 402, Taiwan.
authors.forename: Chi-Ren
authors.initials: CR
authors.lastname: Tsai
mesh_terms: D001208:Asia; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007966:Leukodystrophy, Metachromatic / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D012189:Retrospective Studies; D013624:Taiwan