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Oral Ganglioside Supplement Improves Growth and Development in Patients with Ganglioside GM3 Synthase Deficiency

  • Heng WangEmail author
  • Valerie Sency
  • Paul McJarrow
  • Alicia Bright
  • Qianyang Huang
  • Karen Cechner
  • Julia Szekely
  • JoAnn Brace
  • Andi Wang
  • Danting Liu
  • Angela Rowan
  • Max Wiznitzer
  • Aimin Zhou
  • Baozhong Xin
Research Report
Part of the JIMD Reports book series (JIMD, volume 45)

Abstract

Ganglioside GM3 synthase is a key enzyme involved in the biosynthesis of gangliosides. GM3 synthase deficiency (GM3D) causes an absence of GM3 and all downstream biosynthetic derivatives. The affected individuals manifest with severe irritability, intractable seizures, and profound intellectual disability. The current study is to assess the effects of an oral ganglioside supplement to patients with GM3D, particularly on their growth and development during early childhood. A total of 13 young children, 11 of them under 40 months old, received oral ganglioside supplement through a dairy product enriched in gangliosides, for an average of 34 months. Clinical improvements were observed in most children soon after the supplement was initiated. Significantly improved growth and development were documented in these subjects as average percentiles for weight, height, and occipitofrontal circumference increased in 1–2 months. Three children with initial microcephaly demonstrated significant catch-up head growth and became normocephalic. We also illustrated brief improvements in developmental and cognitive scores, particularly in communication and socialization domains through Vineland-II. However, all improvements seemed transient and gradually phased out after 12 months of supplementation. Gangliosides GM1 and GM3, although measureable in plasma during the study, were not significantly changed with ganglioside supplementation for up to 30 months. We speculate that the downstream metabolism of ganglioside biosynthesis is fairly active and the potential need for gangliosides in the human body is likely substantial. As we search for new effective therapies for GM3D, approaches to reestablish endogenous ganglioside supplies in the affected individuals should be considered.

Keywords

Ganglioside GM3 synthase deficiency ST3GAL5 Treatment 

Notes

Acknowledgments

We thank the families for their patience and support. We appreciate many physicians who provided outstanding and compassionate care to the children affected by the disease. The study was supported in part by Fonterra (via the New Zealand Primary Growth Partnership program, funded by Fonterra Co-operative Group Ltd and the NZ Ministry for Primary Industries) and the Zverina Family Foundation.

Supplementary material

477698_1_En_134_MOESM1_ESM.docx (32 kb)
Supplementary Table 1 Study protocol and flowchart (DOCX 24 kb)
477698_1_En_134_MOESM2_ESM.docx (32 kb)
Supplementary Table 2 Extractions of comments from parents during the study (DOCX 19 kb)
477698_1_En_134_MOESM3_ESM.docx (32 kb)
Supplementary Table 3 Selective Vineland Adaptive Behavior Scales – Second Edition (Vineland-II) in GM3D patients receiving G500 (DOCX 20 kb)

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Copyright information

© Society for the Study of Inborn Errors of Metabolism (SSIEM) 2018

Authors and Affiliations

  • Heng Wang
    • 1
    • 2
    • 3
    • 4
    Email author
  • Valerie Sency
    • 1
  • Paul McJarrow
    • 5
  • Alicia Bright
    • 1
  • Qianyang Huang
    • 6
  • Karen Cechner
    • 1
  • Julia Szekely
    • 1
  • JoAnn Brace
    • 1
  • Andi Wang
    • 1
  • Danting Liu
    • 6
  • Angela Rowan
    • 5
  • Max Wiznitzer
    • 2
    • 3
  • Aimin Zhou
    • 6
  • Baozhong Xin
    • 1
  1. 1.DDC Clinic - Center for Special Needs ChildrenMiddlefieldUSA
  2. 2.Department of PediatricsCase Western Reserve University School of MedicineClevelandUSA
  3. 3.Rainbow Babies & Children’s HospitalClevelandUSA
  4. 4.Department of Molecular CardiologyCleveland ClinicClevelandUSA
  5. 5.Fonterra Research and Development CentrePalmerston NorthNew Zealand
  6. 6.Department of Chemistry, Center for Gene Regulation in Health and DiseasesCleveland State UniversityClevelandUSA

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