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glycine encephalopathy 1 - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

glycine encephalopathy 1

MONDO:0958179

Overview

GeneticsAutosomal recessive · GLDC (chr 9)

ResearchLimited published research (4 articles)

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.

Features include: Lethargy, Encephalopathy, Hyporeflexia, and Seizure and 14 more.

Organ System	Phenotype Count	Example Features
Brain and nerves	8	Encephalopathy, Hyporeflexia, Seizure
Muscles

Genetic Landscape

Assembled from HGNC gene records, ClinGen gene-disease validity evidence, and ClinVar pathogenic variant data. Validity classifications reflect the strength of published evidence linking each gene to this disease.

GLDC encodes glycine decarboxylase (1,020 aa). The glycine cleavage system catalyzes the degradation of glycine. Highest expression in Liver (39.5 TPM) and Cells EBV-transformed lymphocytes (30.1 TPM).

Glycine encephalopathy 1 is associated with mutations in the GLDC gene on chromosome 9.

The GLDC protein participates in Glycine degradation pathway.

GLDC is classified as a druggable target (Enzyme category) with score 8.7.

GeneReviews

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 1. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with nonketotic hyperglycinemia (NKH), the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Source: GeneReviews — "Nonketotic Hyperglycinemia"

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.

No clinical trials have been registered for glycine encephalopathy 1.

4 publications have been identified in PubMed for glycine encephalopathy 1. Research spans Case Report / Case Series (50%), Basic Science / Preclinical (25%), and Epidemiology / Natural History (25%).

Recent Publications

Gowda VK (2025). [PMID: 40840123](https://pubmed.ncbi.nlm.nih.gov/40840123/). *Brain & development*. [Epidemiology / Natural History]
Haddad L (2025). [PMID: 40611912](https://pubmed.ncbi.nlm.nih.gov/40611912/). *Epilepsy Behav Rep*. [Case Report / Case Series]
Yuan F (2025). [PMID: 40225406](https://pubmed.ncbi.nlm.nih.gov/40225406/). *Mol Genet Metab Rep*. [Basic Science / Preclinical]
Ma E (2025). [PMID: 40458115](https://pubmed.ncbi.nlm.nih.gov/40458115/). *AJP Rep*. [Case Report / Case Series]

Data assembled from 6 of 12 sources · Last updated Sep 19, 2026, 4:30 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:605899

Questions for Your Care Team

→Should my partner and I meet with a genetic counselor to discuss carrier status and family planning?
→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 1

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Evaluations Following Initial Diagnosis

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Questions for Your Care Team

Questions for Your Care Team

Clinical Guidance

Explore clinical features

Clinical Guidance

Differential Diagnosis

Clinical Guidance

Therapies Under Investigation

Clinical Trials

glycine encephalopathy 1

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Evaluations Following Initial Diagnosis

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Clinical Guidance

Explore clinical features

Clinical Guidance

Differential Diagnosis

Clinical Guidance

Therapies Under Investigation

Clinical Trials