Glycine encephalopathy

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. 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 on 05-01-20

What is the chance my next child will have glycine encephalopathy if he has a different father?

In autosomal recessive conditions, the chance of the same parents having another affected child is 1 in 4 (25%) with each pregancy. If one of the parents has a child with a different partner, the chance of having another affected child depends on whether the partner is a carrier of the same condition.

We suggest that you consult with a genetics professional to learn more about your chance of having another child with glycine encephalopathy.

Last updated on 05-01-20

What is glycine encephalopathy?

Glycine encephalopathy is an inherited metabolic disease characterized by abnormally high levels of an amino acid called glycine. Glycine is a chemical messenger that transmits signals in the brain. According to the symptoms the disease onset, glycine encephalopathy may be divided in:

  • Classical neonatal form (most common): Symptoms start within a few days of life and may include poor feeding, lack of energy (lethargy), weak muscle tone (hypotonia), hiccups, breathing problems, seizures, hiccups, and coma.
  • Infantile form: Symptoms start only after 6 months of age, as intellectual disability, abnormal movements, and behavioral problems
  • Late onset: Symptoms include tightness or stiffness of the legs or arms (spastic diplegia), and vision loss due to a damage of the eye nerve (optic atrophy).
  • Transient form: Symptoms are similar to the classic form, but glycine levels decrease and the symptoms may improve within time.

Glycine encephalopathy is caused by changes (mutations) in the AMT ,GLDC _or GCSH_ genes which result in a deficiency of the enzyme that break-up the glycine. Diagnosis is based in the symptoms, the high glycine levels and the enzyme deficiency, as well as genetic testing. Inheritance is autosomal recessive. Treatment may include sodium benzoate to reduce the levels of glycine, N-methyl D-aspartate (NMDA) receptor site antagonists, anti-seizure drugs and ketogenic diet. About half of the babies with the classic form, die within a few weeks of life and the survivors may have motor delay, very small head, seizures and stiffness. In the transient form symptoms may improve with time.

Last updated on 05-01-20

Is protein restriction recommended for people with glycine encephalopathy?

Diet restriction alone has not been shown to be effective in improving symptoms of glycine encephalopathy. It is no longer used as a primary method of treatment. Glycine restricted diet in combination with sodium benzoate may be helpful for treating people with severe forms of the condition (who require the maximum or near maximum dose of sodium benzoate). If you have questions or concerns regarding treatment we strongly recommend that you discuss them with a healthcare provider.

Last updated on 05-01-20

What is the prognosis for individuals with glycine encephalopathy?

The prognosis and chance of survivial for an individual affected with glycine encephalopathy depend on the form of the condition the individual has as well as complications that may arise. Preliminary data suggest that the specific mutations that an individual has can somewhat be used to predict the outcome of the disease. Mutations associated with residual enzyme activity (some functioning enzyme present) seem to be associated with a mild outcome, and two known mutations with no residual enzyme activity (no working enzyme present) seem to be associated with a severe outcome. However, because many mutations are "private" (only present in a single family) and some affected individuals die before their outcome is known, it is difficult to predict the outcome for many individuals. The best outcome ever reported is normal intelligence, which has only been seen in individuals who do have some functioning enzyme activity and have had early and aggressive treatment in the first two years of life.

About 85% of individuals affected in the neonatal period (first hours to days of life) have a severe form, and 15% have a mild form. Of the individuals who begin to have signs and symptoms in infancy (the infantile form), about 50% have a severe form and 50% have a mild form. Overall, about 20% of all infants with the neonatal or infant form have a mild outcome. Occasionally, affected individuals have an intermediate outcome between mild and severe.

Individuals with a mild form of the disease can have variable degrees of developmental progress; they may learn to walk, interact with others and attend special education classes. One study found that up to 20% of surviving children learn to walk and say or sign words. These individuals may have little spasticity and they often develop a treatable seizure disorder.

Individuals with a severe form typically do not make developmental progress. At most, they may learn to sit and have very limited interaction with their environment. During the first year of life, they typically develop seizures that become increasingly difficult to treat, usually requiring multiple anticonvulsant medications. They typically have progressive spasticity early on, they have a tendency to develop scoliosis, and they often have swallowing dysfunction that requires tube feeding.

Last updated on 05-01-20

How might glycine encephalopathy be treated?

Currently there is not a cure for glycine encephalopathy. 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.

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. Drug dosage must be individually tailored and requires regular and careful monitoring. Studies regarding the effectiveness of these treatments are ongoing. Mildly affected individuals may receive the greatest benefit from treatment, particularly if treatment is started early.

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.

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 on 05-01-20

Name: Metabolic Support UK 5 Hilliards Court Sandpiper Way
Chester Business Park
Chester, CH4 9QP, United Kingdom
Phone: 0845 241 2173 Toll Free: 0800 652 3181 Email: https://www.metabolicsupportuk.org/contact-us Url: https://www.metabolicsupportuk.org
Name: Nonketotic Hyperglycinemia International Family Network 1401 Ridgefield Avenue
Ocoee, FL, 34761, United States
Phone: 407-484-8479 Email: wolfieworks@juno.com Url: http://www.nkh-network.org
Glycine encephalopathy Genetics Home Reference Website. April 2007; Reference Link Ada Hamosh, Gunter Scharer, Johan Van Hove. Glycine Encephalopathy GeneReviews. July 11, 2013; Reference Link

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