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mitochondrial disease - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

mitochondrial disease

MONDO:0044970

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Overview

OnsetNEONATAL

TreatmentsNo approved treatments · 3 in pipeline

Clinical Trials35 registered · 20 recruiting

Patient Orgs3 organizations · MitoAction, Children’s Mitochondrial Disease Network + 1 more

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

Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency (ECHS1D) has been reported in 40 individuals representing 31 families [, , , , , , , , , , , , ]. ECHS1D represents a clinical spectrum in which several phenotypes have been described. The most common phenotype is presentation in the neonatal period with severe encephalopathy and lactic acidosis and later-onset Leigh-like signs and symptoms. A small number of affected individuals have normal development, exercise-induced dystonia, and basal ganglia abnormalities on MRI . Age of onset is soon after birth in a majority of reported individuals (median age of onset: 1 day; range 1 day – 8 years, n=40); only five reported individuals have presented after the first year of life. In five affected individuals, prenatal signs (intrauterine growth restriction and/or oligohydramnios) were identified; two of those individuals were born prematurely . Common clinical manifestations are summarized in and discussed below. Table 2. Common Clinical Manifestations of ECHS1 Deficiency Clinical Manifestation | Frequency Neurologic1

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

No consensus clinical diagnostic criteria for ECHS1 deficiency (ECHS1D) have been published.

Suggestive Findings

Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency (ECHS1D) should be suspected in individuals with clinical features of Leigh syndrome and/or exercise-induced dystonia who have supportive brain MRI and biochemical findings, including early-onset lactic acidosis.

Clinical features

• Neurologic

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 mitochondrial disease. An additional 3 compounds hold orphan drug designation.

Orphan Drug Designations

While no drugs are FDA-approved specifically for mitochondrial disease, 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 mitochondrial disease. 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

Table 6. Recommended Surveillance for Individuals with ECHS1 Deficiency

Evaluation

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.

35 clinical trials registered, 20 recruiting. Interventions under study include other interventions, drug therapy, medical devices, and gene therapy. Pipeline includes 1 PHASE3, 4 PHASE2, 5 PHASE1. Research is sponsored by a mix of industry and academic institutions.

NCT ID	Title	Phase	Sponsor	Status
[NCT04113447](https://clinicaltrials.gov/study/NCT04113447)

Data assembled from 5 of 12 sources · Last updated Sep 19, 2026, 11:53 AM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Patient Support

Patient Advocacy Groups

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MitoActionPrimary Focus

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Children’s Mitochondrial Disease NetworkPrimary Focus

USWebsite ↗

United Mitochondrial Disease FoundationPrimary Focus

USWebsite ↗

Patient Registry

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Medical References

Questions for Your Care Team

→Are any of the 35 active clinical trials a good fit for my situation?
→With 3 compounds in the orphan drug pipeline, which are furthest along in development and which clinical trials should I be aware of?
→Are there specialists or centers of excellence for this condition in my area?
→How can I connect with MitoAction and other patient organizations for support?

← Back to All Diseases

GeneReviews

Differential Diagnosis

Table 3. Disorders to Consider in the Differential Diagnosis of ECHS1 Deficiency (ECHS1D)

Disorder	Gene(s)	MOI	Clinical Features of Disorder
PDP1	ARXL	Pyruvate dehydrogenase complex deficiency; Lactic acidosis; pyruvate; Nl lactate to pyruvate ratio; Long philtrum; Corpus callosum hypoplasia	May be a complete phenocopy1; Persons w/ECHS1D may have abnl acylcarnitine profile or urine organic acids not typically seen in primary PDCD. 3-hydroxyisobutyryl-CoA hydrolase deficiency (HIBCHD)
HIBCH	AR	Lactic acidosis; Basal gangliar lesions; 2-methyl-2,3-dihydroxybutyrate	Organic acid abnormalities typically more pronounced in HIBCHD FBXL4-related encephalomyopathic mitochondrial DNA depletion syndrome
FBXL4	AR	Neonatal/primary lactic acidosis; Variable cardiomyopathy	FBXL4 deficiency typically has more striking hyperammonemia.; ECHS1D may be suspected (rather than FBXL4 or TMEM70 deficiency) if 2-methyl-2,3-dihydroxybutyrate is present or lactate-to-pyruvate ratio is nl. Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2 (OMIM 614052)
ACAD9 Other Leigh syndromes(See Nuclear Gene-Encoded Leigh Syndrome Overview Mitochondrial DNA-Associated Leigh Syndrome and NARP.)	60 genes	ARmtXL	T2 hyperintensity of the basal ganglia; Dystonia; Developmental regression; Lactic acidosis
SLC2A1	ADAR2	Paroxysmal exercise-induced dystonia	Nl brain MRI Paroxysmal kinesogenic dyskinesia(See PRRT2-Associated Paroxysmal Movement Disorders.)
PRRT2	ADAR2	Paroxysmal dystonia (may be exercise induced)	Nl brain MRI Familial paroxysmal nonkinesigenic dyskinesia
PC	AR	lactate, pyruvate, ammonia	More striking hyperammonemia; Ketonuria AD = autosomal dominant; AR = autosomal recessive; DiffDx = differential diagnosis; MOI = mode of inheritance; mt = mitochondrial; nl = normal; XL = X-linked 1. , 2. Autosomal recessive inheritance is rare.

Source: GeneReviews — "Mitochondrial Short-Chain Enoyl-CoA Hydratase 1 Deficiency"

GeneReviews

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with mitochondrial short-chain enoyl-CoA hydratase 1 deficiency (ECHS1D), the evaluations summarized (if they have not already been completed) are recommended. Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with ECHS1 Deficiency

System/Concern	Evaluation	Comment
Neurologic	Brain MRI/MRS to evaluate for basal ganglia involvement structural brain anomalies	Electroencephalogram to evaluate for epileptic encephalopathy
Cardiovascular	Echocardiogram to evaluate for cardiomyopathy in those w/neonatal form	Measurement of pulmonary artery pressure is important to evaluate for pulmonary hypertension.
Ophthalmologic	Dilated eye exam to evaluate for optic atrophy other findings	In all affected persons
Audiologic	Audiologic eval for sensorineural hearing loss	In all affected persons
Biochemical	Lactate blood gas to evaluate acid/base status	In all affected persons; Blood glucose level; Urine organic acids
Other	Developmental eval	In all affected persons Physical exam consideration of imaging for possible structural anomalies
Treatment of Manifestations in Individuals with ECHS1 Deficiency Manifestation/Concern	Treatment	Comments
Dystonia (paroxysmal)	Benzodiazepines	Levodopa has been tried w/out success in 1 affected person;1 nonetheless, trial of this low-risk, noninvasive therapy is probably reasonable. Dystonia (chronic)
Seizures	Standard anti-seizure therapy	—
Inadequate nutrition	Nasogastric tube or gastrostomy tube; feeding therapy w/speech therapist	Cardiomyopathy or
pulmonary hypertension	Standard treatment per cardiologist	—
Optic atrophy	Low-vision support for educational settings	N-acetylcysteine vitamin C use may be considered, but evidence for benefit is limited.
Sensorineural hearing loss	Hearing aids	See Genetic Hearing Loss Overview
Acidosis	Bicarbonate therapy for correction	Sodium citrate acetate are unlikely to provide sufficient buffering capacity in these children w/secondary impairment of the tricarboxylic acid cycle.
Hyperammonemia2	Correction of metabolic acidosis	High-concentration dextrose would result in lacticemia should be used w/caution if at all. Consideration of hemodialysis

Source: GeneReviews — "Mitochondrial Short-Chain Enoyl-CoA Hydratase 1 Deficiency"

Research Type	Count	% of Total
Laboratory research	176	47%
Research summaries	95	25%
Patient case studies	58	16%
Disease patterns and progression	11	3%
New treatment approaches	11	3%
Clinical study results	9	2%
Testing and diagnosis research	7	2%
Other research	6	2%

Signal abnormalities in the basal ganglia	28/32 (88%)
Growth	Failure to thrive
Cardiovascular	Cardiomyopathy
Ophthalmologic	Nystagmus
Other	Sensorineural hearing loss
Enzymatic	Lactic acidemia

Kisho

mitochondrial disease

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Orphan Drug Designations

Prognosis

Surveillance Guidelines

Research Landscape

Patient Support

Patient Advocacy Groups

Medical References

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Management Guidelines

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications

Latest News & Developments

Comprehensive functional testing in fibroblasts has strong utility to diagnose mitochondrial disease.

Endothelial-mitochondrial coupling in mitochondrial disease: A systematic review and quantitative synthesis of vascular, biochemical, and oxidative bioenergetic dysfunction.

From Single Cells to Diagnosis: Proteomics Technologies in the Multi-Omics Landscape of Rare and Mitochondrial Diseases.

mitochondrial disease

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Orphan Drug Designations

Prognosis

Surveillance Guidelines

Research Landscape

Patient Support

Patient Advocacy Groups

Medical References

Subtypes

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Management Guidelines

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications

Latest News & Developments

Comprehensive functional testing in fibroblasts has strong utility to diagnose mitochondrial disease.

Endothelial-mitochondrial coupling in mitochondrial disease: A systematic review and quantitative synthesis of vascular, biochemical, and oxidative bioenergetic dysfunction.

From Single Cells to Diagnosis: Proteomics Technologies in the Multi-Omics Landscape of Rare and Mitochondrial Diseases.