Glycine Encephalopathy; Hyperglycinemia Nonketotic; Isolated Nonketotic Hyperglycinemia; NKH; Non-ketotic Hyperglycinemia

Nonketotic Hyperglycinemia (NKH) is a genetic disorder characterized by abnormally high levels of glycine, an amino acid that is one of the “building blocks” of proteins. Glycine also acts as a neurotransmitter, which is a chemical messenger that transmits signals in the brain. NKH is caused by mutations in the AMT and GLDC genes, resulting in shortages of an enzyme that normally breaks down glycine in the body. This enzyme deficiency allows excess glycine to build up in tissues and organs, particularly the brain. There are several forms of NKH, which are distinguished by age of onset and severity of symptoms.

Diagnostic testing: A diagnosis of NKH is confirmed by:

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  Enzyme or DNA analysis;

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  Laboratory findings of elevated plasma; and

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  Urine and CSF (cerebral spinal fluid) glycine concentrations.

Physical findings: Individuals with NKH have:

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  Seizures;

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  Brain malformations;

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  Movement disorders (ataxia);

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  Hypotonia (weak muscle tone);

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  Spastic diplegia (spasticity in the muscles of the legs, hips, and pelvis);

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  Optic atrophy (damage to the optic nerves causing progressive vision loss and problems with color vision);

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  Developmental delays; and

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  Intellectual disability.

ICD-9: 270.7

Symptoms of NKH are present at birth with infants showing progressive lack of energy; feeding difficulties; weak muscle tone; abnormal jerking movements; and life threatening problems with breathing. Most children who survive these early signs and symptoms develop profound intellectual disabilities and hard to treat seizures. Mortality is associated with intractable seizures.

Treatment of NKH is symptom specific. During the first two years of life, treatment sodium benzoate to reduce plasma concentration of glycine. Other treatment consisting of antiepileptic drugs for seizures; gastrostomy tube for feeding problems and gastroesophageal reflux; and physical and occupational therapies to improve activities of daily living.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation:

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  Clinical history and examination that describes the diagnostic features and physical findings; and

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  Abnormally elevated levels of glycine in the blood and CSF; and

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  Molecular genetic testing for mutations in the AMT and GLDC genes.

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