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glycine encephalopathy (NKA) - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

glycine encephalopathy

MONDO:0011612

Also known as:NKANonketotic Hyperglycinemianon-ketotic hyperglycinemia

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Overview

Glycine encephalopathy (GE) is an inborn error of glycine metabolism characterized by accumulation of glycine in body fluids and tissues, including the brain, resulting in neurometabolic symptoms of variable severity.

OnsetNEONATAL

TreatmentsNo approved treatments · 1 in pipeline

Clinical Trials1 registered · 1 recruiting

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

No HPO annotations are available for this condition.

Age of onset: newborn period.

GeneReviews

Clinical Guidance

Nonketotic hyperglycinemia (NKH) is the inborn error of glycine metabolism defined by deficient activity of the glycine cleavage enzyme system (GCS), which results in accumulation of large quantities of glycine in all body tissues including the brain. NKH is categorized into severe NKH and attenuated NKH based on ultimate outcome :

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

Suggestive Findings

Nonketotic hyperglycinemia (NKH) due to biallelic pathogenic variants in one of the two genes (GLDC and AMT) known to encode the components of the glycine cleavage enzyme system or possibly in a third gene (GCSH) should be suspected in individuals with the following clinical, laboratory, and neuroimaging findings.

Clinical findings

Source: GeneReviews — "Nonketotic Hyperglycinemia"

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for glycine encephalopathy. An additional 1 compound holds orphan drug designation.

Orphan Drug Designations

While no drugs are FDA-approved specifically for glycine encephalopathy, some of the following designated compounds may be used off-label in clinical practice. Treatment decisions should be made in consultation with a specialist familiar with this condition.

The following drugs have received orphan drug designation from the FDA for glycine encephalopathy. Orphan designation reflects regulatory interest and does not indicate approval for treatment.

Brand Name	Generic Name	Sponsor

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

Surveillance Guidelines

Developmental assessment should be performed throughout the first years of life. Neurologic assessments in the first year can identify early development of spasticity in severely affected individuals and early development of chorea in more mildly affected individuals. Severely affected individuals should be monitored for scoliosis and hip dysplasia. Pulmonary function should be assessed, particularly in children who develop recurrent respiratory infections.

Source: GeneReviews — "Nonketotic Hyperglycinemia"

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

1 clinical trial registered, 1 recruiting. Interventions under study include other interventions. Research is primarily sponsored by academic and government institutions.

40 publications have been identified in PubMed for glycine encephalopathy. Research spans Basic Science / Preclinical (35%), Case Report / Case Series (28%), and Epidemiology / Natural History (13%).

Research Type	Count	% of Total
Laboratory research	14	35%

Data assembled from 6 of 12 sources · Last updated Sep 19, 2026, 9:38 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

Orphanet

European rare disease database

Orphanet:407

GARD

Genetic and Rare Diseases Info Center

GARD:7219

Questions for Your Care Team

→Are any of the 1 active clinical trial a good fit for my situation?
→What is the current development status of glyceryl tribenzoate, and when might it become available?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

← Back to All Diseases

GeneReviews

Differential Diagnosis

Inherited disorders in the differential diagnosis of nonketotic hyperglycinemia (NKH) caused by deficient activity of the glycine cleavage enzyme system (GCS) are outlined in . Table 3. Inherited Disorders in the Differential Diagnosis of NKH

Disorder	Gene(s)	MOI	Clinical Findings	Laboratory Findings
GCS cofactor deficiency1	Lipoate deficiency2	LIAS LIPT2 BOLA3 GLRX5 IBA57	—	—
NFU1	AR	DD, seizures, spasticity, ataxia, optic atrophy, pulmonary hypertension, cardiomyopathy	plasma CSF glycine levels; Deficient GCS activity; Deficient pyruvate dehydrogenase enzyme activity Pyridoxine-dependent epilepsy3	—
ALDH7A1	AR	Neonatal epileptic encephalopathy responsive to pyridoxine treatment	plasma CSF glycine levels; Deficient GCS activity PNPO deficiency3	—
PNPO	AR	Severe neonatal seizures coma; ± apnea; seizures respond to pyridoxal 5'-phosphate treatment.4	CSF glycine levels; Low CSF pyridoxal phosphate PLPBP deficiency3	—
PLPBP	AR	Presentation similar to PNPO deficiency	—	—
Abnormal regulation of GCS	cblX (cobalamin X)5 (See Disorders of Intracellular Cobalamin Metabolism.)	—	—	—
HCFC1	XL	Males: neonatal seizures	plasma CSF glycine levels; Combined methylmalonic aciduria hyperhomocysteinemia	—
Glycine transport defect	GLYT1 encephalopathy (OMIM 617301)	—	—	—
SLC6A9	AR	Neonatal encephalopathy, impaired consciousness, often poor respiratory drive, death usually age 1 yr	CSF glycine (range: 21-33 mol/L); Normal plasma glycine CSF:plasma glycine ratio	—
Inhibition of GCS activity	Organic acidurias6 (e.g., MMA, PA, IVA)	Multiple genes (e.g., PCCA, PCCB, IVD, MMUT [MUT])	Typically AR	Neonatal encephalopathy, metabolic acidosis, hyperammonemia, ketones

Source: GeneReviews — "Nonketotic Hyperglycinemia"

Kisho

glycine encephalopathy

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Orphan Drug Designations

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Management Guidelines

Evaluations Following Initial Diagnosis

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications

glycine encephalopathy

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Orphan Drug Designations

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

Orphanet

GARD

Subtypes

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Management Guidelines

Evaluations Following Initial Diagnosis

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications