The following new article has just been published in Orphanet Journal of Rare Diseases

Research

Late infantile metachromatic leukodystrophy: Clinical manifestations of five Taiwanese patients and Genetic features in Asia

Liaw H, Lee H, Chi C, Tsai C

Orphanet Journal of Rare Diseases 2015, 10 :144 (9 November 2015)

Abstract | Full Text | PDF

Late infantile metachromatic leukodystrophy: Clinical manifestations of five Taiwanese patients and Genetic features in Asia

Hsiang-Ru Liaw²^†, Hsiu-Fen Lee²³^†, Ching-Shiang Chi¹³^* and Chi-Ren Tsai²⁴

*Corresponding author: Ching-Shiang Chi chi-cs@hotmail.com
† Equal contributors

Author Affiliations

¹Department of Pediatrics, Tungs’ Taichung Metroharbor Hospital, 699, Taiwan Boulevard Sec. 8, Wuchi, Taichung 435, Taiwan

²Department of Pediatrics, Taichung Veterans General Hospital, 1650, Taiwan Boulevard Sec. 4, Taichung 40705, Taiwan

³School of Medicine, Chung Shan Medical University, 110, Sec. 1, Jianguo N. Rd, Taichung 40201, Taiwan

⁴Institute of Molecular Biology, National Chung Hsing University, 250, Kuo Kuang Rd, Taichung 402, Taiwan

For all author emails, please log on.

Orphanet Journal of Rare Diseases 2015, 10:144 doi:10.1186/s13023-015-0363-1

Hsiang-Ru Liaw and Hsiu-Fen Lee contributed equally to this work.

The electronic version of this article is the complete one and can be found online at:http://www.ojrd.com/content/10/1/144

Received:	30 June 2015
Accepted:	30 October 2015
Published:	9 November 2015

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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.