Journal of Clinical Pediatrics ›› 2025, Vol. 43 ›› Issue (10): 734-741.doi: 10.12372/jcp.2025.25e0117

• Original Article • Previous Articles     Next Articles

Clinical phenotypes, genetic analysis and allogeneic hematopoietic stem cell transplantation efficacy of 8 children with metachromatic leukodystrophy

HU Jiayue1, YING Lingwen2,3, CHANG Guoying1,2,3, LI Juan2,3, YANG Fan1, WANG Cuijin4, YU Tingting3,5, YAO Ruen3,5, LUO Chengjuan6(), Wang Xiumin1,2,3()   

  1. 1. Department of Clinical Research Ward, Shanghai Children′s Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
    2. Department of Endocrinology and Metabolism, Shanghai Children′s Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
    3. Shanghai Rare Disease Clinical Research Center, Shanghai Children′s Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
    4. Department of Neurology, Shanghai Children′s Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
    5. Department of Genetic and Molecular Diagnosis, Shanghai Children′s Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
    6. Department of Blood and Marrow Transplantation Ceuter, Shanghai Children′s Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
  • Received:2025-02-17 Accepted:2025-05-26 Published:2025-10-15 Online:2025-09-29
  • Contact: LUO Chengjuan, Wang Xiumin E-mail:luochengjuan@scmc.com.cn;wangxiumin1019@126.com

Abstract:

Objective To analyze the clinical characteristics and genetic variations in 8 children with metachromatic leukodystrophy (MLD), and to explore the correlation between genotype and clinical phenotype as well as the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods The study collected data from children diagnosed between 2013 and 2024, confirmed through whole exome sequencing, and found that all children had symptoms such as developmental delay, with ages at diagnosis ranging from 1 year and 3 months to 9 years and 6 months. Results Based on the age of onset and clinical manifestations, 4 cases were late infantile type, with 2 deaths; 4 cases were juvenile type, with a survival rate of 100%. Genetic sequencing revealed compound heterozygous variations in the ARSA gene, a total of 15 mutations, of which 3 were newly reported and all were deleterious variations. Three children received allo-HSCT treatment and all survived but with progression of symptoms. Conclusion MLD mainly manifests as central nervous system damage, and diagnosis should be confirmed in combination with clinical manifestations, ARSA enzyme activity, and genetic testing. Early diagnosis and treatment are crucial for improving prognosis, and allo-HSCT can increase survival rates, but the therapeutic effect is limited.

Key words: metachromatic leukodystrophy, ARSA gene, lysosomal storage disease, allogeneic hematopoietic stem cell transplantation

CLC Number: 

  • R72