AMT-related glycine encephalopathy

What is AMT-related Glycine Encephalopathy?

AMT-related glycine encephalopathy (AMT-related GE) is a disease that impairs the body's ability to metabolize glycine, an amino acid found in proteins. Glycine accumulates in all body tissues, including the brain, and can lead to lethargy, seizures, low muscle tone, breathing difficulties, coma, and often death. Patients who survive with AMT-related GE have intellectual disability and seizures. The majority of patients with AMT-related encephalopathy present in the neonatal period, but there are multiple forms of the condition described.

The neonatal form of this disease presents in the first hours to days of life with rapid progression of symptoms. The infantile onset form is characterized by developmental delays and infantile-onset seizures at approximately 6 months of age. Other atypical types of AMT-related GE appear later in childhood or adulthood and cause a variety of medical problems that primarily affect the nervous system.

How common is AMT-related Glycine Encephalopathy?

Glycine encephalopathy affects approximately 1 in 250,000 live births in the United States. The incidence of glycine encephalopathy is higher in certain populations such as British Columbia (1 in 63,000) and in Finland (1 in 55,000). Approximately 15-20% of individuals with glycine encephalopathy have mutations in the AMT gene.

How is AMT-related Glycine Encephalopathy treated?

There is no cure for glycine encephalopathy. Disease management is aimed at trying to reduce the accumulation of glycine in the body. Glycine plasma concentrations can be reduced by sodium benzoate and low protein diet. Seizures are addressed with anticonvulsant medications, but may not be completely effective for all individuals.

What is the prognosis for a person with AMT-related Glycine Encephalopathy?

About 85% of those with neonatal onset and 50% of those with the infantile onset will have severe symptoms. These infants typically will have profound intellectual disability and will have seizures that are difficult to treat. Death in the first year is common in these individuals.

Approximately 20% of all children affected with glycine encephalopathy will have less severe symptoms. These individuals will have moderate intellectual disability. They are often able to communicate (most often non-verbally), and typically have seizures that respond to treatment. These children may develop movement disorders and behavioral problems.

Rarely, affected individuals present with late-onset glycine encephalopathy, in which symptoms appear usually after one year of age. These individuals typically have some intellectual disability, and seizures are uncommon.