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glutaryl-CoA dehydrogenase deficiency (GA1) - Clinical Profile, Genes & Research | Kisho | Kisho

Features include always present findings: Elevated urine 3-hydroxyglutaric level, Reduced peroxisomal glutaryl-CoA oxidase activity, and Elevated circulating glutarylcarnitine concentration; and very common findings: Glutaric aciduria, Enlarged sylvian cistern, Abnormal basal ganglia morphology, and Abnormal circulating enzyme concentration or activity. 73 total HPO annotations.

Organ System	Phenotype Count	Example Features
Brain and nerves	29	Encephalopathy, Acute encephalopathy, Inability to walk
Muscles	4	Low muscle tone (hypotonia), Generalized hypotonia, Brain shrinkage (cerebral atrophy)
Digestive system	3	Enlarged liver (hepatomegaly), Difficulty swallowing (dysphagia), Feeding difficulties
Lab test results	2	Elevated circulating glutaric acid concentration, Elevated circulating glutarylcarnitine concentration
Head and neck	2	Macrocephaly, Progressive macrocephaly
Bones and joints	2	Severe backward arching of the body (opisthotonus), Joint dislocation
Growth and development	1	Failure to thrive
Metabolism	1	Metabolic acidosis
Skin	1	Subependymal nodules
Heart and blood vessels	1	Widened subarachnoid space
Eyes	1	Retinal hemorrhage
Lungs and breathing	1	Abnormality of the respiratory system
Ears	1	Vertigo
Arms and legs	1	Limb dystonia
Kidneys and urinary system	1	Chronic kidney disease

GeneReviews

Clinical Guidance

The phenotypic spectrum of untreated glutaric acidemia type 1 (GA-1) ranges from the more common form (infantile-onset disease) to the less common form (later-onset disease after age 6 years). Of note, the GA-1 phenotype can vary widely among untreated family members with the same genotype, primarily as a function of the age at which the first acute encephalopathic crisis occurred: three months to three years in infantile-onset GA-1 and after age six years in later-onset GA-1 . Characteristically these crises result in acute bilateral striatal injury and subsequent complex movement disorders. Patients may also develop insidious-onset basal ganglia injury in the absence of an identified acute encephalopathic crisis.

Source: GeneReviews — "Glutaric Acidemia Type 1"

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

Guidelines for diagnosis and management of glutaric acidemia type 1 (GA-1) due to deficiency or absence of functional glutaryl-CoA dehydrogenase were developed in 2007 and recently revised .

Suggestive Findings

Scenario 1: Positive Newborn Screening (NBS)

GA-1 should be suspected in infants with a positive NBS result. NBS for GA-1 primarily relies on measuring glutarylcarnitine (C5DC) in dried blood spots, which has been shown to have 96% sensitivity . Positive C5DC values (i.e., those above the cutoff reported by the screening laboratory) require follow-up biochemical testing with either urine organic analysis or quantitative glutaric and 3-hydroxyglutaric acid, with preference for quantitative studies if available.

Source: GeneReviews — "Glutaric Acidemia Type 1"

GeneReviews

Differential Diagnosis

Table 2. Other Genes of Interest in the Differential Diagnosis of Glutaric Acidemia Type 1 (GA-1)

Gene(s)	DiffDx Disorder	MOI	Clinical Features of DiffDx Disorder
Significantoverlappingfeatures	Other clinical features	Laboratory/Imaging findings ETFA ETFB	—
ETFDH	Glutaric acidemia type 2 (See Multiple Acyl-CoA Dehydrogenase Deficiency.)

Glutaryl-CoA dehydrogenase deficiency is included in newborn screening programs (Glutaric Acidemia Type I) in all 50 states and 3 territories.

Genetic testing for GCDH is available. Testing is considered confirmatory for diagnosis.

Biomarker and diagnostic research for glutaryl-CoA dehydrogenase deficiency has been reported in the published literature.

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 glutaryl-CoA dehydrogenase deficiency. An additional 1 compound holds orphan drug designation.

Orphan Drug Designations

While no drugs are FDA-approved specifically for glutaryl-CoA dehydrogenase deficiency, 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 glutaryl-CoA dehydrogenase deficiency. Orphan designation reflects regulatory interest and does not indicate approval for treatment.

Brand Name	Generic Name	Sponsor	Designated	Exclusivity End	Designation Status
adeno-associated viral vector 9 delivering human Glutaryl-CoA Dehydrogenase (GCDH) gene	adeno-associated viral vector 9 delivering human Glutaryl-CoA Dehydrogenase (GCDH) gene	Shanghai Vitalgen BioPharma Co., Ltd.	2022	—	Designated

Gene therapy approaches for glutaryl-CoA dehydrogenase deficiency have been reported in the published literature.

GeneReviews

Management Guidelines

When glutaric acidemia type 1 (GA-1) is suspected during the diagnostic evaluation (i.e., due to elevated concentration of 3-OH-GA in plasma or urine), metabolic treatment should be initiated immediately. Development and evaluation of treatment plans, training and education of affected individuals and their families, and avoidance of side effects of dietary treatment (i.e., malnutrition, growth failure) require a multidisciplinary approach to care including multiple subspecialists, with oversight and expertise from a specialized metabolic center. The second revision of consensus clinical practice guidelines for the treatment of individuals with GA-1 have recently been published .

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual following diagnosis of GA-1, the evaluations summarized (if not performed as part of the evaluation that led to diagnosis) are recommended.

Table 3.

Recommended Evaluations Following Initial Diagnosis of GA-1

Evaluation | Comment

Consultation w/metabolic physician / biochemical geneticist specialist metabolic dietician1 | • Transfer to specialist center w/experience in management of inherited metabolic diseases is strongly recommended.

Consider short hospitalization at center of expertise for inherited metabolic conditions to provide detailed education (natural history, maintenance emergency treatment, prognosis, risks for acute encephalopathic crises) for caregivers.

Source: GeneReviews — "Glutaric Acidemia Type 1"

GeneReviews

Clinical Guidance

Avoid the following:

Excessive dietary protein or protein malnutrition inducing catabolic state
Prolonged fasting
Catabolic illness (intercurrent infection; brief febrile illness post-vaccination)
Inadequate caloric provision during other stressors, especially when fasting is involved (surgery or procedure requiring fasting/anesthesia)

Although there are no data on which to base such a recommendation, given the increased risk of subdural hemorrhage in individuals with GA-1, avoidance or extreme caution with contact sports and physical activities that involve high risk for minor head injuries would appear to be a sensible precaution.

Source: GeneReviews — "Glutaric Acidemia Type 1"

Clinical Trials

3 trials found

Explore Trials

Prognosis

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

GeneReviews

Surveillance Guidelines

Regular evaluations by a metabolic specialist and metabolic dietician are appropriate. See for additional recommended surveillance. Table 9. Recommended Surveillance for Individuals with Glutaric Aciduria Type 1

Manifestation/Concern	Evaluation	Frequency/Comment
Poor growth	Measurement of growth, weight, head circumference	At each visit
Delayed acquisition of developmental milestones	Monitor developmental milestones.	At each visit Neuropsychological testing using age-appropriate standardized assessment batteries
Movement disorder	Assessment for clinical symptoms signs of movement disorders, severity, responses to treatment, physical therapy, pharmacologic interventions	At each visit
Abnormal amino acid levels (amino acid deficiencies lysine)	Quantitative analysis of plasma amino acids (ideally obtained after a 3-hr protein fast)1	1st year of life: at least every 3 mos; Ages 1-6 yrs: every 6 mos; 6 yrs of age: annually
Nutritional deficiencies2	Calcium, phosphorus, vitamin D, prealbumin, B12, zinc, ferritin	If clinically indicated3
Chronic renal insufficiency4	Plasma creatinine /or cystatin C level	Periodically in adolescents adults
Anemia	Complete blood count, ferritin level	If clinically indicated3
Abnormal liver function	ALT/AST , albumin	If clinically indicated3
Head injury5 /or rapid head growth6	Consider head MRI.	If clinically indicated7 ALT = alanine transaminase; AST = aspartate transaminase 1. Correlations between plasma lysine concentration and dietary lysine intake are often poor . 2.

Source: GeneReviews — "Glutaric Acidemia Type 1"

Phenotype severity distribution: 3 always present features, 4 very common features, 23 common features.

Estimated prevalence: Unknown (Unknown prevalence).

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.

3 clinical trials registered, 2 recruiting. Interventions under study include other interventions and biologic therapy. Pipeline includes 1 PHASE1. Research is sponsored by a mix of industry and academic institutions.

67 publications have been identified in PubMed for glutaryl-CoA dehydrogenase deficiency. Research spans Case Report / Case Series (27%), Basic Science / Preclinical (18%), and Epidemiology / Natural History (15%).

Research Type	Count	% of Total
Patient case studies	18	27%
Laboratory research	12	18%
Disease patterns and progression	10	15%
Testing and diagnosis research	9	13%
Research summaries	7	10%
Clinical study results	5	7%
New treatment approaches	5	7%
Other research	1	1%

Recent Publications

Veronelli L (2026). [PMID: 41779049](https://pubmed.ncbi.nlm.nih.gov/41779049/). *Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology*. [Review / Meta-Analysis]
Wang S (2026). [PMID: 42108166](https://pubmed.ncbi.nlm.nih.gov/42108166/). *Prenat Diagn*. [Diagnostic / Biomarker]
Beyzaei Z (2026). [PMID: 42074598](https://pubmed.ncbi.nlm.nih.gov/42074598/). *Genes (Basel)*. [Basic Science / Preclinical]
Selamioğlu A (2026). [PMID: 42210298](https://pubmed.ncbi.nlm.nih.gov/42210298/). *Ital J Pediatr*. [Basic Science / Preclinical]
Wah IYM (2026). [PMID: 41582531](https://pubmed.ncbi.nlm.nih.gov/41582531/). *Hong Kong medical journal = Xianggang yi xue za zhi*. [Case Report / Case Series]
Saad C (2026). [PMID: 41917075](https://pubmed.ncbi.nlm.nih.gov/41917075/). *Sci Rep*. [Gene Therapy / Novel Therapeutics]
Soliman Y (2026). [PMID: 42158588](https://pubmed.ncbi.nlm.nih.gov/42158588/). *BMJ Neurol Open*. [Review / Meta-Analysis]
Mujamammi AH (2026). [PMID: 41893363](https://pubmed.ncbi.nlm.nih.gov/41893363/). *Metabolites*. [Diagnostic / Biomarker]
Preisner F (2026). [PMID: 41485880](https://pubmed.ncbi.nlm.nih.gov/41485880/). *Journal of inherited metabolic disease*. [Basic Science / Preclinical]
Gala F (2026). [PMID: 41669735](https://pubmed.ncbi.nlm.nih.gov/41669735/). *Journal of the Korean Society of Radiology*. [Gene Therapy / Novel Therapeutics]

Kisho

glutaryl-CoA dehydrogenase deficiency

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Genetic Landscape

Diagnosis

Diagnostic Criteria

Scenario 1: Positive Newborn Screening (NBS)

Differential Diagnosis

Treatment

Orphan Drug Designations

Management Guidelines

Evaluations Following Initial Diagnosis

Clinical Guidance

Clinical Trials

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

glutaryl-CoA dehydrogenase deficiency

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Genetic Landscape

Diagnosis

Diagnostic Criteria

Scenario 1: Positive Newborn Screening (NBS)

Differential Diagnosis

Treatment

Orphan Drug Designations

Management Guidelines

Evaluations Following Initial Diagnosis

Clinical Guidance

Clinical Trials

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Orphanet

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team