UCL Great Ormond Street Institute of Child Health


Great Ormond Street Institute of Child Health


Non-Ketotic Hyperglycinemia

Non-ketotic hyperglycinemia (NKH), or glycine encephalopathy, is a rare, autosomal recessive disease characterised by accumulation of glycine in body fluids and tissues. The disease typically becomes apparent soon after birth with progressive lethargy and severe neurological symptoms, including intractable seizures, developmental delay and psychomotor retardation. Current treatments not effective long-term and are not curative.

NKH is caused by mutations in genes (GLDC or AMT) encoding the glycine cleavage system (GCS), a component of mitochondrial folate metabolism. Current projects make use of a novel mouse model, in which reduced expression of the NKH-causing gene Gldc (encoding glycine decarboxylase) causes loss of GCS activity and features of NKH including elevated glycine in urine and plasma, hydrocephalus and early lethality (Pai 2015).

A proportion of GCS-deficient mice (lacking Amt or Gldc) also develop NTDs, confirming the involvement of this enzyme system in defects of pre-natal and post-natal development of the central nervous system (Narisawa 2012).

Our research aims to better understand the disease process and to develop novel therapies. Current projects include:

  • Using mass spectrometry assays to determine metabolic effects of GCS deficiency
  • Investigating neurological deficits at a cellular and functional level
  • Evaluating small molecules treatment for reduction of glycine & normalisation of folate metabolism
  • Testing conditional genetic rescue as a proof of principle for gene therapy

Further information can be found on the Action Medical Research website

  • In parallel, we are developing a zebrafish model for GCS-deficiency as a further model system (with Paula Alexandre) - Newlife

Recent Publications

Narisawa A., Komatsuzaki S., Kikuchi A.,Niihori T., Aoki Y., Fujiwara K.,Tanemura M., Hata A., Suzuki Y., Relton C.R., Grinham J., Leung K-Y, Partridge D., Robinson A., Stone V., Gustavsson P., Stanier P., Copp A.J., Greene N.D.E., Tominaga T., Matsubara Y., Kure S. Mutations in genes encoding the glycine cleavage system predispose to neural tube defects in mice and humans. Hum. Mol. Genet. 21: 1496-1503, 2012 (PDF).

Pai YJ, Leung K-Y, Savery D, Hutchin T, Prunty H, Heales S, Brosnan ME, Brosnan JT, Copp AJ, Greene NDE. Glycine decarboxylase deficiency causes neural tube defects and features of non-ketotic hyperglycinemia in mice. Nat. Commun. 6: 6388, 2015 (PDF).

NKH Conference 2017

This year's Nonketotic Hyperglycinemia Conference will be held at the UCL Great Ormond Street Institute of Child Health. This event is specifically for families of children diagnosed with NKH   Further information on the schedule of speakers and to register for NKH 2017.

Research Funded By: