Clinical and molecular investigation in Chinese patients with glutaric aciduria type I

Clin Chim Acta. 2016 Jan 30:453:75-9. doi: 10.1016/j.cca.2015.12.003. Epub 2015 Dec 4.

Abstract

Glutaric aciduria type I (GA-I) is a rare autosomal recessive metabolic disorder caused by deficiency of glutaryl-CoA dehydrogenase (GCDH), leading to an abnormal metabolism of lysine, hydroxylysine and tryptophan. It results in accumulations of glutaric acid, 3-hydroxyglutaric acid and glutaconic acid. Clinical features include the sudden onset of encephalopathy, hypotonia and macrocephaly usually before age 18months. Here we report five cases of GA-I confirmed with mutation analysis. GCDH gene mutations were identified in all five probands with GA-I. Three of them had compound heterozygous mutations and two had homozygous mutations. Mutations of two alleles (c.334G>T and IVS11-11A>G) were novel and both of them were confirmed to be splice site mutations by reverse transcription PCR.

Keywords: GCDH; Glutaric aciduria type I; Newborn screening; Splice site mutation.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Metabolism, Inborn Errors / diagnosis*
  • Amino Acid Metabolism, Inborn Errors / enzymology
  • Amino Acid Metabolism, Inborn Errors / genetics*
  • Amino Acid Metabolism, Inborn Errors / metabolism
  • Base Sequence
  • Brain Diseases, Metabolic / diagnosis*
  • Brain Diseases, Metabolic / enzymology
  • Brain Diseases, Metabolic / genetics*
  • Brain Diseases, Metabolic / metabolism
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • Glutarates / metabolism
  • Glutaryl-CoA Dehydrogenase / chemistry
  • Glutaryl-CoA Dehydrogenase / deficiency*
  • Glutaryl-CoA Dehydrogenase / genetics
  • Glutaryl-CoA Dehydrogenase / metabolism
  • Heterozygote
  • Humans
  • Male
  • Models, Molecular
  • Mutation
  • Protein Conformation

Substances

  • 3-hydroxyglutaric acid
  • Glutarates
  • Glutaryl-CoA Dehydrogenase
  • glutaric acid

Supplementary concepts

  • Glutaric Acidemia I