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Glycine encephalopathy


Other Names for this Disease

  • Glycine synthase deficiency
  • Hyperglycinemia nonketotic
  • Nonketotic hyperglycinemia
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.

Overview

What is glycine encephalopathy?

What are the signs and symptoms of glycine encephalopathy?

How is glycine encephalopathy inherited?

How might glycine encephalopathy be treated?

What is glycine encephalopathy?

Glycine encephalopathy is an inherited condition characterized by abnormally high levels of an amino acid called glycine. Glycine acts as a chemical messenger that transmits signals in the brain. Glycine encephalopathy is caused by the shortage of an enzyme that normally breaks down glycine in the body, thus allowing excess glycine to build up in tissues and organs, particularly the brain. Symptoms typically appear during infancy or early childhood and include a lack of energy (lethargy), feeding difficulties, weak muscle tone (hypotonia), abnormal jerking movements, breathing problems, seizures, and intellectual disability. It is caused by mutations in the AMT, GLDC or GCSH genes and is inherited in an autosomal recessive manner.[1][2]
Last updated: 11/10/2011

What are the signs and symptoms of glycine encephalopathy?

Most individuals with glycine encephalopathy begin to show signs and symptoms in the first hours or first days of life (the neonatal period). Of these affected individuals, approximately 85% have a neonatal severe form, and 15% have a neonatal mild form. The signs and symptoms often include progressive lack of energy (lethargy), feeding difficulties, poor muscle tone (hypotonia), abnormal jerking movements (myoclonic jerking) and life-threatening breathing problems such as apnea.[3][1] Infants that survive this period typically have severe intellectual disability and seizures that are difficult to control.[3] Affected males are more likely to survive and tend to have more mild developmental problems than affected females, although the reason for this is unclear.[1] In rare instances, the main features of the condition improve with time; in these cases, the condition is known as transient glycine encephalopathy because glycine decreases to normal or near-normal levels after being very high at birth. Many children with the transient form will develop normally and experience few long-term medical problems, but some individuals may continue to have intellectual disability or seizures even after glycine levels decrease.[1]

There have been affected individuals with "atypical" forms of the condition with variable signs and symptoms; these forms have ranged from milder disease with onset from late infancy to adulthood, to rapidly progressing and severe disease with late onset.[1][3] The most common "atypical" form is known as the infantile form and is characterized by hypotonia, developmental delay and seizures. Individuals with this form may develop normally until signs and symptoms begin at approximately 6 months of age. As they age, many of these individuals develop intellectual disability, abnormal movements and behavioral problems. Other atypical forms of glycine encephalopathy can appear later in childhood or adulthood and cause a variety of medical problems that primarily affect the nervous system.[1]
Last updated: 10/31/2011

How is glycine encephalopathy inherited?

Glycine encephalopathy is inherited in an autosomal recessive pattern, which means in an affected individual, both copies of the gene that cause this condition have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene and are referred to as carriers. Carriers typically do not show signs and symptoms of the condition.[4] When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% chance to not have the condition and not be a carrier.
Last updated: 10/28/2011

How might glycine encephalopathy be treated?

Currently there is not a cure for glycine encephalopathy.[2][5] All but very mildly or atypically affected individuals develop intellectual disability and seizures, even with treatment. Treatment options for people with glycine encephalopathy may vary depending on the severity of their condition. Tests, such as MRI and EEG, as well as evaluations of development and neurological function can help determine the severity of the condition in an infant, child, or adult.[2]

The goal of treatment is to reduce the amount of glycine in the plasma (blood). Treatment may involve a medication called sodium benzoate, which binds with glycine allowing it to be passed out in the urine, and dextromethorphan, ketamine, or felbamate, which block some of the harmful effects of excessive glycine. These treatments may help control seizures, increase alertness, and in mildly affected individuals, improve behavior.[2]  Drug dosage must be individually tailored and requires regular and careful monitoring.[2][5] Studies regarding the effectiveness of these treatments are ongoing.[2] Mildly affected individuals may receive the greatest benefit from treatment, particularly if treatment is started early.[2]

Other treatments include drugs to control seizures (anti-epileptic drugs); assistive devices or surgeries to aid with feeding and swallowing (e.g., gastrostomy tube); physical therapy; and scoliosis management. Parents and family members may benefit from genetic counseling. Click here to learn more about genetic consultations.[2]

For further details on treatment, please visit the following link to GeneReviews. GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions. Because of the complexity of the information in the article, we recommend that you review it with a health care provider.
http://www.ncbi.nlm.nih.gov/books/NBK1357/#nkh.Management

Last updated: 11/10/2011

References
  1. Glycine encephalopathy. Genetics Home Reference. April 2007; http://ghr.nlm.nih.gov/condition/glycine-encephalopathy. Accessed 10/28/2011.
  2. Hamosh A, Scharer G, Van Hove J. Glycine encephalopathy. GeneReviews. November 2009. ; http://www.ncbi.nlm.nih.gov/books/NBK1357/. Accessed 11/10/2011.
  3. Ada Hamosh, Gunter Scharer, Johan Van Hove. Glycine Encephalopathy. GeneReviews. November 24, 2009; http://www.ncbi.nlm.nih.gov/books/NBK1357/. Accessed 10/28/2011.
  4. Glycine encephalopathy. Genetics Home Reference Website. April 2007; http://ghr.nlm.nih.gov/condition=glycineencephalopathy. Accessed 10/7/2008.
  5. Van Hove JL, Vande Kerckhove K, Hennermann JB, Mahieu V, Declercq P, Mertens S, De Becker M, Kishnani PS, Jaeken J. Benzoate treatment and the glycine index in nonketotic hyperglycinaemia. J Inherit Metab Dis. 2005;28(5):651-63; http://www.ncbi.nlm.nih.gov/pubmed/16151895. Accessed 8/26/2011.


Other Names for this Disease
  • Glycine synthase deficiency
  • Hyperglycinemia nonketotic
  • Nonketotic hyperglycinemia
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.