Open Access

Metachromatic leukodystrophy: Characterization of two (p.Leu433Val, p.Gly449Arg) arylsulfatase A mutations

  • Authors:
    • Yangyang Wang
    • Xiang Chen
    • Chan Liu
    • Shamin Wu
    • Qingfeng Xie
    • Quan Hu
    • Shan Chen
    • Yiwei Liu
  • View Affiliations

  • Published online on: July 9, 2019     https://doi.org/10.3892/etm.2019.7760
  • Pages: 1738-1744
  • Copyright : © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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Abstract

Metachromatic leukodystrophy disorder (MLD) is an autosomal recessive lysosomal storage disease. The disease is primarily caused by a deficiency in the enzyme arylsulfatase A (ASA), which is encoded by the ARSA gene. A total of 254 mutations have been reported in different populations. The present study aimed to detect causative gene mutations in an atypical case presenting with attention deficit hyperactivity disorder through whole‑exome sequencing. Of note, the patient's mother is from a consanguineous family. Compound heterozygous variants (c.1297C>G) + (c.1345G>A) [(p.Leu433Val) + (p.Gly449Arg)] were identified in exon 8 in the ARSA gene of the pediatric patient. The two missense mutations identified have not been previously reported, to the best of our knowledge. Furthermore, an in silico analysis and multiple phylogenetic tree analyses of ARSA homologs were performed to predict the effects of the two novel mutations. Serial changes were observed in the patient with MLD at follow‑up visits over 6 years. However, brain MRI images demonstrated no notable progression and the number of ASA enzymes was stable. Also, the results of neurodevelopmental assessment showed that the patient was diagnose with ADHD. These data may offer a potential explanation of the genotype‑phenotype correlation in MLD and enhance the spectrum of mutations associated with the condition.

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September 2019
Volume 18 Issue 3

Print ISSN: 1792-0981
Online ISSN:1792-1015

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APA
Wang, Y., Chen, X., Liu, C., Wu, S., Xie, Q., Hu, Q. ... Liu, Y. (2019). Metachromatic leukodystrophy: Characterization of two (p.Leu433Val, p.Gly449Arg) arylsulfatase A mutations. Experimental and Therapeutic Medicine, 18, 1738-1744. https://doi.org/10.3892/etm.2019.7760
MLA
Wang, Y., Chen, X., Liu, C., Wu, S., Xie, Q., Hu, Q., Chen, S., Liu, Y."Metachromatic leukodystrophy: Characterization of two (p.Leu433Val, p.Gly449Arg) arylsulfatase A mutations". Experimental and Therapeutic Medicine 18.3 (2019): 1738-1744.
Chicago
Wang, Y., Chen, X., Liu, C., Wu, S., Xie, Q., Hu, Q., Chen, S., Liu, Y."Metachromatic leukodystrophy: Characterization of two (p.Leu433Val, p.Gly449Arg) arylsulfatase A mutations". Experimental and Therapeutic Medicine 18, no. 3 (2019): 1738-1744. https://doi.org/10.3892/etm.2019.7760