[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Conditions](https://durgical.com/en/conditions/) › Glycine encephalopathy (nonketotic hyperglycinaemia) [Conditions](https://durgical.com/en/conditions/) · [Metabolism (biochemistry)](https://durgical.com/en/conditions/) # Glycine encephalopathy (nonketotic hyperglycinaemia) The brain cannot break down glycine, which builds up and overstimulates nerve receptors: newborns are floppy, stop breathing and have seizures. Updated 2026-11-01 ## Structures involved Tap one to see what it is and open it in 3D. - [Corpus callosum](https://durgical.com/en/anatomy/corpus-callosum/) - [White matter](https://durgical.com/en/anatomy/white-matter-of-telencephalon/) - [Medulla oblongata](https://durgical.com/en/anatomy/medulla-oblongata/) - [Pons](https://durgical.com/en/anatomy/pons/) - [Spinal cord](https://durgical.com/en/anatomy/spinal-cord/) ## What it is An inherited defect of the mitochondrial glycine cleavage system that causes glycine to accumulate in the brain and other tissues. ## Who gets it At least 1 in 76,000 people worldwide (about 1 in 55,000 newborns in Finland). About 80 % of cases are due to GLDC and 20 % to AMT. No Colombian figures are published. ## Causes - Autosomal recessive variants in GLDC (P protein) or AMT (T protein) of the glycine cleavage system ## Risk factors - Carrier parents; consanguinity - Affected sibling ## Pathophysiology The glycine cleavage system (P, T, H and L proteins; needs pyridoxal phosphate, tetrahydrofolate, lipoic acid and NAD⁺) splits glycine into CO₂, NH₃ and a one-carbon unit on tetrahydrofolate. When it fails, glycine rises in plasma and even more in cerebrospinal fluid. In the brainstem and [spinal cord](https://durgical.com/en/anatomy/spinal-cord/) glycine is an inhibitory transmitter, causing hypotonia, apnoea and hiccups; in the cortex it is a co-agonist of NMDA receptors, so excess glycine drives seizures and excitotoxic brain damage. No ketoacidosis occurs, which distinguishes it from the organic acidaemias. ## Classification - Severe neonatal form: lethargy, apnoea, intractable seizures, profound disability - Attenuated form: later onset, developmental delay, milder seizures, behaviour problems - Transient neonatal form (rare), which resolves ## Symptoms and signs - Lethargy and poor feeding in the first days of life - Very low muscle tone - Apnoea needing breathing support - Persistent hiccups - Myoclonic seizures ## Red flags - Newborn with apnoea, hypotonia and myoclonic jerks without acidosis or high ammonia ## Diagnosis **Clinical** Neonatal encephalopathy with hypotonia, apnoea, hiccups and myoclonic seizures; EEG with a burst-suppression pattern. **Tests** Simultaneous plasma and CSF glycine with a raised CSF-to-plasma glycine ratio; normal organic acids (no ketoacidosis); GLDC and AMT gene testing. Valproate must be avoided before testing because it raises glycine. **Imaging** Brain MRI: thin or short [corpus callosum](https://durgical.com/en/anatomy/corpus-callosum/) and restricted diffusion in myelinated tracts. ## Treatment **Acute** Breathing support and seizure control in neonatal intensive care **Medical** Sodium benzoate, which binds glycine and removes it in urine as hippurate, adjusted to plasma glycine levels **Medical** NMDA receptor blockers (dextromethorphan; ketamine in some centres) to reduce excitotoxicity **Rehabilitation** Physiotherapy and developmental support **Follow-up** Monitoring of plasma glycine, seizures, feeding and growth ## Complications - Profound intellectual disability - Drug-resistant epilepsy - Spasticity and feeding difficulties - Death in infancy in severe forms ## Prognosis Poor in the severe form; better in the attenuated form, depending on the gene variants. ## Test yourself Think of the answer, then tap the question to see it. ## Which enzyme system is defective in glycine encephalopathy? The mitochondrial glycine cleavage system, usually its P protein (GLDC) or T protein (AMT). ## Which laboratory ratio supports the diagnosis? A raised CSF-to-plasma glycine ratio in simultaneously taken samples. ## Why is the disease called 'nonketotic'? To separate it from ketotic hyperglycinaemia of propionic and methylmalonic acidaemia, which cause ketoacidosis. ## How does sodium benzoate lower glycine? It is conjugated with glycine to form hippurate, which is excreted in urine. ## Why does excess glycine cause both apnoea and seizures? It is inhibitory in the brainstem and spinal cord (apnoea, hypotonia) but co-activates NMDA receptors in the cortex (seizures). [Add to my cards (5)](https://durgical.app/estudiar/?add=/en/conditions/glycine-encephalopathy/) ## Related conditions - [Propionic acidaemia](https://durgical.com/en/conditions/propionic-acidaemia/) - [Methylmalonic acidaemia](https://durgical.com/en/conditions/methylmalonic-acidaemia/) - [Epilepsy and seizures](https://durgical.com/en/conditions/epilepsy-and-seizures/) Educational information, not medical advice. For any symptom, see a health professional. Sources: [Nonketotic hyperglycinemia: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/nonketotic-hyperglycinemia/) (MedlinePlus, US National Library of Medicine, 2026); [GLDC gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/gldc/) (MedlinePlus, US National Library of Medicine, 2026); [AMT gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/amt/) (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011). [← All conditions](https://durgical.com/en/conditions/) ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/conditions/glycine-encephalopathy/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/glycine-encephalopathy/