d-Glyceric aciduria does not cause nonketotic hyperglycinemia: A historic co-occurrence

Mol Genet Metab. 2017 Jun;121(2):80-82. doi: 10.1016/j.ymgme.2017.04.009. Epub 2017 Apr 20.


Historically, d-glyceric aciduria was thought to cause an uncharacterized blockage to the glycine cleavage enzyme system (GCS) causing nonketotic hyperglycinemia (NKH) as a secondary phenomenon. This inference was reached based on the clinical and biochemical results from the first d-glyceric aciduria patient reported in 1974. Along with elevated glyceric acid excretion, this patient exhibited severe neurological symptoms of myoclonic epilepsy and absent development, and had elevated glycine levels and decreased glycine cleavage system enzyme activity. Mutations in the GLYCTK gene (encoding d-glycerate kinase) causing glyceric aciduria were previously noted. Since glycine changes were not observed in almost all of the subsequently reported cases of d-glyceric aciduria, this theory of NKH as a secondary syndrome of d-glyceric aciduria was revisited in this work. We showed that this historic patient harbored a homozygous missense mutation in AMT c.350C>T, p.Ser117Leu, and enzymatic assay of the expressed mutation confirmed the pathogeneity of the p.Ser117Leu mutation. We conclude that the original d-glyceric aciduria patient also had classic NKH and that this co-occurrence of two inborn errors of metabolism explains the original presentation. We conclude that no evidence remains that d-glyceric aciduria would cause NKH.

Keywords: AMT; Epilepsy; GLYCTK; Inborn errors of metabolism; Nonketotic hyperglycinemia; d-Glycerate kinase deficiency; d-Glyceric aciduria.

Publication types

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

MeSH terms

  • Amino Acid Oxidoreductases / genetics
  • Amino Acid Oxidoreductases / metabolism
  • Aminomethyltransferase / genetics
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Diagnosis, Differential
  • Epilepsy
  • Glyceric Acids / metabolism
  • Glyceric Acids / urine*
  • Glycine / metabolism
  • Homozygote
  • Humans
  • Hyperglycinemia, Nonketotic / complications*
  • Hyperglycinemia, Nonketotic / diagnosis
  • Hyperglycinemia, Nonketotic / etiology
  • Hyperglycinemia, Nonketotic / genetics
  • Hyperoxaluria, Primary / complications*
  • Hyperoxaluria, Primary / diagnosis
  • Hyperoxaluria, Primary / genetics*
  • Male
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism
  • Mutation, Missense
  • Phosphotransferases (Alcohol Group Acceptor) / deficiency
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Transferases / genetics
  • Transferases / metabolism


  • Carrier Proteins
  • Glyceric Acids
  • Multienzyme Complexes
  • glycine cleavage system
  • glyceric acid
  • Amino Acid Oxidoreductases
  • Transferases
  • Aminomethyltransferase
  • Phosphotransferases (Alcohol Group Acceptor)
  • glycerate kinase
  • Glycine

Supplementary concepts

  • Primary hyperoxaluria type 2