Early growth and development impairments in patients with ganglioside GM3 synthase deficiency

Clin Genet. 2016 May;89(5):625-9. doi: 10.1111/cge.12703. Epub 2016 Jan 20.

Abstract

Ganglioside GM3 synthase is a key enzyme involved in the biosynthesis of gangliosides. GM3 synthase deficiency (GSD) causes a complete absence of GM3 and all downstream biosynthetic derivatives. The individuals affected by this disorder manifest severe irritability, intractable seizures and profound intellectual disability. However, we have found that most newborns seem symptom-free for a period of time after birth. In order to further understand the onset of the disease, we investigated the early growth and development of patients with this condition through this study. We compared 37 affected individuals with their normal siblings and revealed that all children with GSD had relatively normal intrauterine growth and development, as their weight, length and head circumference were similar to their normal siblings at birth. However, the disease progresses quickly after birth and causes significant constitutional impairments of growth and development by 6 months of age. Neither breastfeeding nor gastrostomy tube placement made significant difference on growth and development as all groups of patients showed the similar pattern. We conclude that GSD causes significant postnatal growth and developmental impairments and the amount of gangliosides in breast milk and general nutritional intervention do not seem to alter these outcomes.

Keywords: ST3GAL5; ganglioside GM3 synthase deficiency; mutation; phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Birth Weight / genetics
  • Body Weight / genetics
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Disease Progression
  • Epilepsy / genetics*
  • Epilepsy / pathology
  • Female
  • Fetal Development / genetics*
  • G(M3) Ganglioside / metabolism*
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mutation
  • Sialyltransferases / deficiency*
  • Sialyltransferases / genetics
  • Siblings

Substances

  • G(M3) Ganglioside
  • Sialyltransferases
  • haematoside synthetase

Supplementary concepts

  • Amish Infantile Epilepsy Syndrome