Kisho

Kisho is an information platform, not a medical provider. Nothing on this site constitutes medical advice, diagnosis, or treatment recommendations. All content is aggregated from publicly available sources (including ClinicalTrials.gov, PubMed, FDA.gov, and Orphanet) and is provided for informational purposes only. Clinical trial eligibility, treatment decisions, and any health-related actions should always be discussed with a qualified healthcare professional. Kisho does not endorse any specific therapy, organization, or clinical trial. Terms of use · Privacy policy

3-methylglutaconic aciduria - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

3-methylglutaconic aciduria

MONDO:0017359

Overview

A group of five inherited disorders caused by mutations in the AUH, DNAJC19, OPA3, and TAZ genes. The disorders are characterized by impairment in the function of mitochondria, resulting in the accumulation and excretion of 3-methylglutaconic acid, and the presence of 3-methylglutaric acid in the urine.

OnsetNEONATAL, ADULT

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, adulthood.

GeneReviews

Clinical Guidance

Barth syndrome is characterized by cardiomyopathy (almost always present before age five years and typically dilated cardiomyopathy with or without endocardial fibroelastosis or left ventricular noncompaction); neutropenia (most often associated with bacterial infections and aphthous ulcers); myopathy (predominantly affecting the proximal muscles); developmental delay; and prepubertal growth delay. Not all features may be present in a given individual. The vast majority of individuals with Barth syndrome are male; rarely, heterozygous females manifest findings of Barth syndrome. Affected Males To date, approximately 230-250 individuals with Barth syndrome have been identified . The vast majority of affected individuals are male (see also ). The following description of the phenotypic features associated with this condition is based on these reports . Table 3. Barth Syndrome: Select Features

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

For the purposes of this GeneReview, the terms "male" and "female" are narrowly defined as the individual's biological sex at birth as it determines clinical care . No consensus clinical diagnostic criteria for Barth syndrome have been published.

Suggestive Findings

Barth syndrome should be suspected in probands with the following clinical and supportive laboratory findings and family history. Clinical findings in infancy (age 0-12 months)

Source: GeneReviews — "Barth Syndrome"

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 3-methylglutaconic aciduria. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

No clinical practice guidelines for Barth syndrome have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with Barth syndrome, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 5. Barth Syndrome: Recommended Evaluations Following Initial Diagnosis

Prognosis

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

GeneReviews

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Table 9. Barth Syndrome: Recommended Surveillance

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 3-methylglutaconic aciduria.

19 publications have been identified in PubMed for 3-methylglutaconic aciduria. Research spans Case Report / Case Series (65%), Basic Science / Preclinical (18%), and Diagnostic / Biomarker (6%).

Research Type	Count	% of Total
Patient case studies	11	65%

Data assembled from 4 of 12 sources · Last updated Sep 18, 2026, 7:13 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

Orphanet

European rare disease database

Orphanet:289902

GARD

Genetic and Rare Diseases Info Center

GARD:12966

Questions for Your Care Team

→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

Feature	% of Persons w/Feature1	Comment
Cardiomyopathy	91%-95%	Findings may be undulating.
Neutropenia	70%-86%	Neutropenia may be intermittent.
Myopathy	72%-100%	Proximal myopathy is common.
Developmental delay	66%-72%	—
Growth delay	58%	Based on Most individuals with Barth syndrome present in infancy or early childhood with symptomatic dilated cardiomyopathy. Manifestations often include tachypnea, tachycardia, and difficulty with feeding and weight gain.

GeneReviews

Differential Diagnosis

Increased urinary excretion of the branched-chain organic acid 3-methylglutaconate (3-MGC) is a relatively common finding in children investigated for suspected inborn errors of metabolism. 3-MGC is an intermediate of leucine degradation and the mevalonate shunt pathway that links sterol synthesis with mitochondrial acetyl-coenzyme A metabolism. A classification of inborn errors of metabolism with 3-methylglutaconic aciduria (3-MGCA) as the discriminative feature was published by and . Clinical features and biochemical findings of syndromes associated with 3-MGCA vary. Tissues with higher requirements for oxidative metabolism, such as the central nervous system and cardiac and skeletal muscle, are predominantly affected. Cardiomyopathy. Left ventricular noncompaction (LVNC) is seen in other genetic syndromes as an isolated finding or associated with other congenital cardiac malformations. Other genes in which pathogenic variants can lead to isolated cardiomyopathy with left ventricular noncompaction include those listed in . Neutropenia. The differential diagnosis for isolated neutropenia is wide and includes several notable genetic conditions . Table 4. Barth Syndrome: Genetic Disorders of Interest in the Differential Diagnosis

Discriminating Feature	Gene	Disorder	MOI	Key Clinical Characteristics (In Addition to Discriminating Feature)/ Comment
AGK	Sengers syndrome (See Mitochondrial DNA Maintenance Defects Overview.)	AR	Myopathy, hypotonia, hypertrophic cardiomyopathy, cataracts, DD2	—
ATAD3A	Harel-Yoon syndrome (OMIM 617183)	ADAR	DD, hypotonia, optic atrophy, axonal neuropathy, hypertrophic cardiomyopathy3	—
AUH	3-methylglutaconic aciduria type I (AUH defect) (OMIM 250950)	AR	Adult-onset progressive spasticity dementia w/characteristic slowly developing radiologic picture of extensive leukoencephalopathy4,5 CLPB	—
CLPB deficiency	ARAD	Severe CLPB deficiency: death usually occurs at a few mos of age due to significant neonatal neurologic involvement severe neutropenia assoc w/life-threatening infections.	—	—
DNAJC19	3-methylglutaconic aciduria type V (DNAJC19 defect) (OMIM 610198)	AR	Characteristic combination of childhood-onset dilated cardiomyopathy, nonprogressive cerebellar ataxia, testicular dysgenesis, poor growth	—
HTRA2	HTRA2 deficiency (See Nuclear Gene-Encoded Leigh Syndrome Spectrum Overview.)	AR	Cataracts, central hypopnea, DD ID, epilepsy, movement disorder, neutropenia	—
MICOS13	Combined oxidative phosphorylation deficiency 37 (OMIM 618329)	AR	Hypotonia, poor weight gain, neurodegenera...	—

Source: GeneReviews — "Barth Syndrome"

System/Concern	Evaluation	Comment
Constitutional	Measurement of growth parameters	Consider plotting on Barth syndrome-specific growth charts.1
Cardiac	Electrocardiography	To evaluate for hypertrophy, QTc, arrythmia Echocardiography
Neutropenia	Complete blood count w/differential	To evaluate for neutropenia
Gastrointestinal	Gastroenterology/ nutrition/ feeding team eval	To incl eval of weight gain nutritional status; Consider eval for gastrostomy tube placement in those w/poor weight gain.
Neuromuscular	Neurologic exam	For signs of muscle weakness hypotonia
Development	Developmental assessment	To incl motor, adaptive, cognitive assessments; Eval based on age for early intervention/ IEP /or 504 plan Genetic
counseling	By genetics professionals2	To obtain a pedigree inform affected persons their families re nature, MOI, implications of Barth syndrome to facilitate medical personal decision making Family support
resources	By clinicians, wider care team, family support organizations	Assessment of family social structure to determine need for:; Community or such as Parent to Parent; Social work involvement for parental support; Home nursing referral IEP = individual education plan; MOI = mode of inheritance 1.
Barth Syndrome: Targeted Therapy Treatment	Dosage	Indication
Elamipretide	40 mg subcutaneously daily1	Improvement of muscle strength2
Barth Syndrome: Treatment of Manifestations Manifestation/Concern	Treatment	Considerations/Other
Heart failure	Standard treatment1 incl careful fluid volume mgmt avoidance of overdiuresis dehydration	Standard HF medications are used to improve symptoms, effect reverse remodeling of ventricle, improve ventricular function as measured by EF.2
arrhythmia	Consideration of antiarrhythmic medications or ICD	Use of these therapies prophylactically for prevention of primary arrhythmia has not been clarified.

Kisho

3-methylglutaconic aciduria

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications

Latest News & Developments

Gene therapy for children with sickle cell disease approved by FDA

3-methylglutaconic aciduria

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

Orphanet

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications

Latest News & Developments

Gene therapy for children with sickle cell disease approved by FDA