Non-Ketotic Hyperglycinemia Details

Expanded Description

Non-Ketotic Hyperglycinemia is a rare autosomal recessive metabolic disorder characterized by abnormally high levels of the amino acid glycine. Glycine acts as a neurotransmitter, which is a chemical messenger that transmits signals in the brain. NKH is caused by the shortage of an enzyme that normally breaks down glycine in the body. A lack of this enzyme allows excess glycine to build up in tissues and organs, particularly the brain, leading to serious medical problems.

Prevalence

0.2 ( Per 100,000 Population ) [Source]

Causes

Non-Ketotic Hyperglycinemia is caused by a shortage of the enzyme that normally breaks down glycine in the body. An autosomal recessive metabolic disorder caused by deficiencies in the mitochondrial GLYCINE cleavage system; an enzyme system with four components: P-, T-, H-, and L-proteins. Deficiency of the P-protein is the most prevalent form. Neonatal and juvenile presentations have been reported. Neonatal onset is more common and may be fatal. Both parents are carriers of the gene.

Disorder Symptoms

There are several symptoms that affect people with Non-Ketotic Hyperglycinemia.

Name	Description
Listlessness	Listlessness
Spasticity	Spasticity
Seizures	Seizures
Involuntary muscle contractions	Involuntary muscle contractions
Opisthotonos	Opisthotonos
Hiccups	Hiccups
Apnea	Apnea
Failure to thrive	Failure to thrive
Mental retardation	Moderate to Severe mental retardation
Progressive spastic diplegia	Progressive spastic diplegia in late onset form
Optic atrophy	Optic atrophy in late onset form
Convulsions	Convulsions
Poor feeding	Poor feeding
Vomiting	Vomiting
High level of glycine	High level of glycine in urine, in plasma, and in cerebrospinal fluid.
Reduced muscle tone	Reduced muscle tone

Diagnosis

1.Diagnostic
elevated levels of glycine in the plasma, cerebral spinal fluid (CSF), and urine
high CSF/plasma glycine ratio
deficiency of the hepatic glycine cleavage enzyme system activity on samples collected by liver biopsy
prenatal
deficiency of the enzyme system activity in cultured chorionic villi
2. Serum
some organic acidemias can cause hyperglycinemia (i.e., propionic and methylmalonic acidemias) and should be ruled out by serum and urine amino acid and organic acid determinations
normal serum pH with no ketoacidosis
3. EEG
diffusely abnormal
hypsarrhythmia and/or burst-suppression pattern may be present
4. CT/MRI
cerebral atrophy
delayed myelination

Diagnostic Tests

No diagnostic test information has been added yet.

We don't have any tests yet.

Disorder Treatments

1. Supportive:
multidisciplinary approach
Pediatrics, Neurology, PT
genetic counseling, P/T, O/T, speech therapy

2. Medical:
Convert Glycine to an Excretable Compound
a. Sodium Benzoate
conjugates with glycine and excreted as hippuric acid
reduces both plasma and CSF glycine concentrations
clinical benefit more apparent in milder form of the disease
b. Dextromethorphan (DM)
glycine accumulation in the CNS may stimulate N-methyl-D-asparate (NMDA) receptors leading to increased excitatory activity with subsequent impairment of neuronal functions and synaptic development
DM is a NMDA receptor antagonist and may diminish certain neurological manifestations
c. Anticonvulsant Therapy
indicated

3. Diet:
protein restriction may be indicated

We don't have any treatments yet.

Prognosis

Patients usually die in the newborn period. Those that survive the newborn period are usually severely mentally impaired with seizures and spasticity if not treated medically. Some patients can learn to hold their head up, sit, walk, communicate, and eat orally. All children are affected to varying degrees of disabilities and abilities.

Tips for Living with the Disorder

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