Nonketotic Hyperglycinemia (NKH)
Also known as: NKH; Glycine Encephalopathy
Nonketotic Hyperglycinemia, or NKH, is a metabolic disorder that affects how we process glycine, an amino acid.
NKH is caused by mutations in one of two genes (AMT or GLDC). Genes are segments of DNA that tell cells how to make proteins. NKH genes create proteins that make the Glycine Cleavage System, which breaks down glycine and provides one-carbon folate molecules. NKH occurs when mutations produce unstable or nonfunctional proteins, preventing the Glycine Cleavage System from processing glycine, causing toxic levels in the body and reducing the supply of one-carbon folate molecules.
Children who cannot process any glycine have severe NKH. Those who process a small amount have attenuated NKH, which ranges across poor, intermediate, and mild forms.
NKH is life-limiting. Around one in three children do not survive their first year. For those with severe NKH, the median age of death is four to eight years, though some children live to teenage years or older.
In this article
What are the symptoms of Nonketotic Hyperglycinemia (NKH)?
In the neonatal period, a newborn with NKH might be floppy and lethargic, and their condition can worsen to apnea or respiratory failure, infantile spasms, jerky movements, or coma.
In older children, common symptoms of severe NKH can include:
- intractable seizures (intractable means they don’t respond to medication)
- limited cognitive development/profound intellectual disability
- limited motor development (such as poor voluntary control of arms and hands, and
delayed or absent head control, severe delay in rolling over, unlikely to sit independently, crawl, stand or walk). - movement disorders such as hypotonia, dystonia or spasticity.
- Cortical vision impairment, strabismus, and/or nystagmus
- Extreme lethargy (often sleeping)
Attenuated (mild) NKH may include these, as well as delayed developmental milestones, learning disabilities, hyperactivity, attention difficulties, and/or behavioral challenges.
What are the causes of Nonketotic Hyperglycinemia (NKH)?
NKH is an autosomal recessive disorder. This means, to have NKH, a child must have two copies of a mutated NKH gene (AMT or GLDC). Children with NKH typically inherit mutations from their parents, who carry one mutation each. There is a one-in-four chance carriers will have a child affected by NKH.
How is Nonketotic Hyperglycinemia (NKH) diagnosed?
Clinical diagnosis happens by detecting elevated glycine levels in both blood/plasma levels and cerebrospinal fluid (CSF), with an abnormally high CSF-to-plasma glycine ratio. The diagnosis is confirmed by identifying mutations in the glycine-cleavage system genes with genetic testing.
How is Nonketotic Hyperglycinemia (NKH) treated?
Unfortunately, there is no cure for NKH. Treatment includes Sodium Benzoate (to help reduce glycine levels in plasma/blood), and dextromethorphan (to help preserve neurone function in the brain), but while these medications help, they do not prevent NKH symptoms. Management involves a variety of medical, educational and social support. Individuals will need to be managed by a multidisciplinary team of specialists who can help support their medical, educational and social care needs.
Inheritance patterns and prenatal diagnosis of Nonketotic Hyperglycinemia (NKH)
Prenatal diagnosis
For a naturally conceived pregnancy, there are two tests that can be done to check if the baby has NKH:
- A CVS (Chorionic villus sampling) test can be carried out between the 11th and 14th weeks of pregnancy, where a small sample of cells will be removed from the placenta These cells are tested for NKH genetic mutations.
- An amniocentesis test can be carried out between the 15th and 20th weeks of pregnancy, where a small sample of amniotic fluid (fluid that surrounds your baby) is removed for analysis. The cells found in this sample are tested for NKH genetic mutations.
For an assisted conception via IVF, once the embryos have been fertilised and matured, a small number of cells are taken from the embryo and genetically tested for NKH. Embryos that are unaffected or carriers are able to be transferred to mature into pregnancy.
Support for people affected by Nonketotic Hyperglycinemia (NKH) and their families
If your child is affected by a medical condition or disability, we can help. Call our freephone helpline on 0808 808 3555 to get information, support and advice. We also offer emotional support for parents via our Listening Ear service.
We have a range of parent guides on aspects of caring for a disabled child in our resource library. You may also find our Early Years Support useful, which contains links to parent carer workshops and help for families going through the diagnosis process.
We’ve listed a support group below and you can also meet other parents online in our closed Facebook group.
The Mikaere Foundation
Helpline: 0330 088 7313
Email: [email protected]
Website: http://www.mikaerefoundation.org
The Mikaere Foundation is a national organisation supporting children and families impacted by Nonketotic Hyperglycinemia (NKH).
Group details added May 2026.
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Credits
Medical text written by The Mikaere Foundation March 2026 and reviewed by their medical advisors Prof Nick Greene (Director of Research at Great Ormond Street Institute of Child Health, and Professor of Developmental Neurobiology, at UCL, lead of the NKH Research Team), and Dr James Davison (Consultant in Paediatric Metabolic Medicine at GOSH, and Chair of the British Inherited Metabolic Diseases Group)
Although great care has been taken in the compilation and preparation of all entries to ensure accuracy, we cannot accept responsibility for any errors or omissions. Any medical information provided is for education/information purposes and is not designed to replace medical advice by a qualified medical professional.