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.^[1][2]  According to the symptoms the disease onset, glycine encephalopathy may be divided in:^[3][2]

• 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.^[2][1] 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.^[1] 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.^[3]

 

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.

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.

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.