MGCA3
MCID: 3MT016
MIFTS: 66

3-Methylglutaconic Aciduria, Type Iii (MGCA3)

Categories: Eye diseases, Genetic diseases, Metabolic diseases, Nephrological diseases, Neuronal diseases, Rare diseases
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Aliases & Classifications for 3-Methylglutaconic Aciduria, Type Iii

MalaCards integrated aliases for 3-Methylglutaconic Aciduria, Type Iii:

Name: 3-Methylglutaconic Aciduria, Type Iii 57 39 38
Optic Atrophy 11 75 28 53 5 43 14 71 31 33
3-Methylglutaconic Aciduria Type 3 11 24 42 58 28 5 14 71
Costeff Syndrome 57 11 24 19 42 58 73 75
Mga3 57 11 19 42 58 73
Costeff Optic Atrophy Syndrome 11 19 42 58 73
Infantile Optic Atrophy with Chorea and Spastic Paraplegia 11 19 42 58
Optic Atrophy Plus Syndrome 57 19 42 73
Autosomal Recessive Optic Atrophy Plus Syndrome 11 19 58
Autosomal Recessive Optic Atrophy Type 3 11 19 58
3-Methylglutaconic Aciduria Type Iii 11 19 42
Opa3 Defect 24 19 42
Iraqi Jewish Optic Atrophy Plus 19 42
Mga, Type Iii 57 42
Mga Type Iii 19 73
Mgca3 57 73
Optic Atrophy, Infantile, with Chorea and Spastic Paraplegia 57
Optic Atrophy Infantile with Chorea and Spastic Paraplegia 19
3-Alpha Methylglutaconic Aciduria Type Iii 19
Opa3-Related 3-Methylglutaconic Aciduria 39
3-Alpha-Methylglutaconic Aciduria Type 3 73
Optic Atrophy 3, Autosomal Recessive 57
Autosomal Recessive Optic Atrophy 3 42
Optic Atrophy 3 Autosomal Recessive 73
Iraqi-Jewish 'optic Atrophy Plus' 57
Iraqi-Jewish Optic Atrophy Plus 11
3-Methylglutaconic Aciduria 3 73
Atrophy, Optic, Plus Syndrome 38
Second Cranial Nerve Atrophy 33
Second Cranium Nerve Atrophy 33
Opa3, Autosomal Recessive 57
Autosomal Recessive Opa3 42
Primary Optic Atrophy 33
Atrophy of Optic Disc 11
Oa - [optic Atrophy] 33
Optic Nerve Atrophy 33
Optic Atrophy 3 19
Atrophy, Optic 38

Characteristics:


Inheritance:

3-Methylglutaconic Aciduria, Type Iii: Autosomal recessive 57
3-Methylglutaconic Aciduria Type 3: Autosomal recessive 58

Age Of Onset:

3-Methylglutaconic Aciduria Type 3: Childhood 58

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
onset of optic atrophy in infancy or early childhood
neurologic features occur later in childhood
increased prevalence in individuals of jewish-iraqi origin
allelic disorder to autosomal dominant optic atrophy and cataract


Classifications:

Orphanet: 58  
Rare eye diseases
Inborn errors of metabolism


External Ids:

Disease Ontology 11 DOID:0110004 DOID:5723
OMIM® 57 258501
OMIM Phenotypic Series 57 PS250950
ICD9CM 34 377.1
NCIt 49 C34863
SNOMED-CT 68 155188004
ICD10 31 H47.2 H48.0
MESH via Orphanet 44 C535311
ICD10 via Orphanet 32 E71.1
UMLS via Orphanet 72 C0574084
Orphanet 58 ORPHA67047
MedGen 40 C0574084
UMLS 71 C0029124 C0574084

Summaries for 3-Methylglutaconic Aciduria, Type Iii

MedlinePlus Genetics: 42 Costeff syndrome is an inherited condition characterized by vision loss, delayed development, and movement problems. Vision loss is primarily caused by degeneration (atrophy) of the optic nerves, which carry information from the eyes to the brain. This optic nerve atrophy often begins in infancy or early childhood and results in vision impairment that worsens over time. Some affected individuals have rapid and involuntary eye movements (nystagmus) or eyes that do not look in the same direction (strabismus).Development of motor skills, such as walking, is often delayed in people with Costeff syndrome. Affected individuals may also have speech difficulties (dysarthria). While some people with Costeff syndrome have mild to moderate intellectual disability, many have normal intelligence.Movement problems in people with Costeff syndrome develop in late childhood and include muscle stiffness (spasticity), impaired muscle coordination (ataxia), and involuntary jerking movements (choreiform movements). As a result of these movement difficulties, individuals with Costeff syndrome may require wheelchair assistance.Costeff syndrome is associated with increased levels of a substance called 3-methylglutaconic acid in the urine (3-methylglutaconic aciduria). The amount of this substance does not appear to influence the signs and symptoms of the condition. Costeff syndrome is one of a group of metabolic disorders that can be diagnosed by the presence of 3-methylglutaconic aciduria. People with Costeff syndrome also have high levels of another acid called 3-methylglutaric acid in their urine.

MalaCards based summary: 3-Methylglutaconic Aciduria, Type Iii, also known as optic atrophy, is related to leber hereditary optic neuropathy, modifier of and optic atrophy 7 with or without auditory neuropathy, and has symptoms including ataxia, abnormality of extrapyramidal motor function and muscle spasticity. An important gene associated with 3-Methylglutaconic Aciduria, Type Iii is OPA3 (Outer Mitochondrial Membrane Lipid Metabolism Regulator OPA3), and among its related pathways/superpathways are Glucose / Energy Metabolism and Miro GTPase Cycle. The drugs Iron and Acetylcysteine have been mentioned in the context of this disorder. Affiliated tissues include eye, retina and brain, and related phenotypes are visual impairment and choreoathetosis

OMIM®: 57 3-Methylglutaconic aciduria type III (MGCA3) is a neuroophthalmologic syndrome consisting of early-onset bilateral optic atrophy and later-onset spasticity, extrapyramidal dysfunction, and cognitive deficit. Urinary excretion of 3-methylglutaconic acid and of 3-methylglutaric acid is increased (Anikster et al., 2001). The phenotype is similar to Behr syndrome (210000) and may in some cases represent the same disorder (Sheffer et al., 1992; Lerman-Sagie, 1995). For a discussion of genetic heterogeneity of 3-methylglutaconic aciduria, see MGCA type I (250950). (258501) (Updated 08-Dec-2022)

UniProtKB/Swiss-Prot: 73 An autosomal recessive metabolic disorder that causes a neuro- ophthalmologic syndrome consisting of early-onset bilateral optic atrophy, spasticity, extrapyramidal dysfunction and cognitive deficit. Urinary excretion of 3-methylglutaconic acid and 3-methylglutaric acid is increased. MGCA3 can be distinguished from MGCA1 by the absence of increase of 3-hydroxyisovaleric acid levels.

Disease Ontology 11 3-methylglutaconic aciduria type 3: A 3-methylglutaconic aciduria that has material basis in mutation in the OPA3 gene.

Optic atrophy: An optic nerve disease that is characterized the death of the retinal ganglion cell axons that comprise the optic nerve.

GARD: 19 3-methylglutaconic aciduria type III (MGA III) is an organic aciduria characterised by the association of optic atrophy and choreoathetosis with 3-methylglutaconic aciduria.

Orphanet: 58 3-methylglutaconic aciduria type III (MGA III) is an organic aciduria characterised by the association of optic atrophy and choreoathetosis with 3-methylglutaconic aciduria.

Wikipedia 75 Costeff syndrome: Costeff syndrome, or 3-methylglutaconic aciduria type III, is a genetic disorder caused by mutations in... more...

Optic atrophy: Optic neuropathy is damage to the optic nerve from any cause. The optic nerve is a bundle of millions of... more...

GeneReviews: NBK1473

Related Diseases for 3-Methylglutaconic Aciduria, Type Iii

Diseases in the 3-Methylglutaconic Aciduria, Type Iii family:

3-Methylglutaconic Aciduria, Type I 3-Methylglutaconic Aciduria, Type Iv
3-Methylglutaconic Aciduria, Type V 3-Methylglutaconic Aciduria, Type Viib
3-Methylglutaconic Aciduria, Type Viii 3-Methylglutaconic Aciduria, Type Ix
3-Methylglutaconic Aciduria, Type Viia 3-Methylglutaconic Aciduria

Diseases related to 3-Methylglutaconic Aciduria, Type Iii via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 829)
# Related Disease Score Top Affiliating Genes
1 leber hereditary optic neuropathy, modifier of 33.9 WFS1 TMEM126A OPA3 OPA1 MTRFR MFN2
2 optic atrophy 7 with or without auditory neuropathy 33.5 WFS1 TMEM126A OPA3 OPA1 AFG3L2
3 optic atrophy 2 33.5 OPA2 MECR
4 autosomal dominant optic atrophy plus syndrome 33.5 OPA1 MFN2
5 optic atrophy 11 33.4 OPA1 MICOS13 MFN2 MFN1 AFG3L2
6 wolfram syndrome 33.4 WFS1 TMEM126A OPA3
7 optic atrophy 5 33.4 OPA1 AFG3L2
8 optic atrophy 6 33.4 WFS1 TMEM126A OPA6 OPA3
9 optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy 33.4 WFS1 OPA1 AFG3L2
10 optic atrophy 9 33.3 OPA3 OPA1 AFG3L2
11 optic atrophy 10 with or without ataxia, mental retardation, and seizures 33.3 OPA1 MFN2 AFG3L2
12 optic atrophy 4 33.1 OPA4 OPA3
13 behr syndrome 33.0 TMEM126A OPA3 OPA1 MTRFR MFN2 AFG3L2
14 optic atrophy 1 32.7 OPA6 OPA1
15 infantile cerebellar-retinal degeneration 32.5 WFS1 TMEM126A
16 pontocerebellar hypoplasia, type 1e 32.5 WFS1 TMEM126A OPA3 MFN2
17 leigh syndrome 32.4 OPA1 MTRFR MFN2 MFN1
18 spastic paraplegia 55, autosomal recessive 32.3 OPA3 MTRFR
19 charcot-marie-tooth disease type 2a2b 32.1 MFN2 MFN1
20 wolfram syndrome 2 32.0 WFS1 TMEM126A
21 neuropathy 31.9 WFS1 OPA1 MTRFR MFN2 AFG3L2
22 3-methylglutaconic aciduria 31.6 OPA3 MTRFR MICOS13
23 optic atrophy 3, autosomal dominant 31.6 TMEM126A OPA3 OPA1 MFN2 MFN1
24 peripheral nervous system disease 31.5 WFS1 OPA3 OPA1 MFN2 MFN1
25 kearns-sayre syndrome 31.5 OPA3 OPA1 MTRFR MFN2 AFG3L2
26 scotoma 31.5 TMEM126A OPA3 OPA1
27 hereditary spastic paraplegia 31.1 OPA3 OPA1 MTRFR MFN2 MFN1 AFG3L2
28 tritanopia 31.1 TMEM126A OPA3
29 mitochondrial myopathy 31.0 OPA1 MFN2 MFN1 AFG3L2
30 optic nerve disease 30.8 WFS1 TMEM126A OPA3 OPA1 MTRFR MFN2
31 neuropathy, hereditary motor and sensory, type via, with optic atrophy 30.7 TMEM126A OPA3 MTRFR MFN2
32 charcot-marie-tooth disease type 2a2a 30.6 MTRFR MFN2
33 spinocerebellar ataxia 28 30.5 OPA3 AFG3L2
34 toxic optic neuropathy 30.5 TMEM126A OPA3 MFN2
35 bosch-boonstra-schaaf optic atrophy syndrome 11.8
36 peho syndrome 11.7
37 gapo syndrome 11.7
38 spastic paraplegia, optic atrophy, and neuropathy 11.7
39 dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities 11.7
40 arts syndrome 11.6
41 optic atrophy 12 11.6
42 auditory neuropathy and optic atrophy 11.6
43 mitochondrial myopathy, episodic, with or without optic atrophy and reversible leukoencephalopathy 11.6
44 neuropathy, hereditary motor and sensory, type vic, with optic atrophy 11.6
45 leber optic atrophy and dystonia 11.6
46 optic atrophy 13 with retinal and foveal abnormalities 11.6
47 encephalopathy, progressive, with amyotrophy and optic atrophy 11.6
48 optic atrophy 8 11.6
49 spastic paraplegia 79, autosomal recessive 11.6
50 neurodegeneration with ataxia and late-onset optic atrophy 11.6

Graphical network of the top 20 diseases related to 3-Methylglutaconic Aciduria, Type Iii:



Diseases related to 3-Methylglutaconic Aciduria, Type Iii

Symptoms & Phenotypes for 3-Methylglutaconic Aciduria, Type Iii

Human phenotypes related to 3-Methylglutaconic Aciduria, Type Iii:

58 30 (show all 18)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 visual impairment 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000505
2 choreoathetosis 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0001266
3 3-methylglutaconic aciduria 58 30 Very rare (1%) Very frequent (99-80%)
HP:0003535
4 intellectual disability 58 30 Frequent (33%) Frequent (79-30%)
HP:0001249
5 nystagmus 58 30 Frequent (33%) Frequent (79-30%)
HP:0000639
6 ataxia 58 30 Frequent (33%) Frequent (79-30%)
HP:0001251
7 dysarthria 58 30 Frequent (33%) Frequent (79-30%)
HP:0001260
8 spastic paraparesis 58 30 Frequent (33%) Frequent (79-30%)
HP:0002313
9 gait disturbance 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001288
10 optic atrophy 30 Very rare (1%) HP:0000648
11 3-methylglutaric aciduria 30 Very rare (1%) HP:0003344
12 spasticity 30 HP:0001257
13 hyperreflexia 30 HP:0001347
14 chorea 30 HP:0002072
15 cognitive impairment 30 HP:0100543
16 reduced visual acuity 30 HP:0007663
17 abnormality of extrapyramidal motor function 30 HP:0002071
18 babinski sign 30 HP:0003487

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Neurologic Central Nervous System:
spasticity
hyperreflexia
ataxia
dysarthria
extrapyramidal signs
more
Laboratory Abnormalities:
increased urinary 3-methylglutaconic acid

Head And Neck Eyes:
optic atrophy
decreased visual acuity

Clinical features from OMIM®:

258501 (Updated 08-Dec-2022)

UMLS symptoms related to 3-Methylglutaconic Aciduria, Type Iii:


ataxia; abnormality of extrapyramidal motor function; muscle spasticity

Drugs & Therapeutics for 3-Methylglutaconic Aciduria, Type Iii

Drugs for 3-Methylglutaconic Aciduria, Type Iii (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 56)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Iron Approved Phase 2, Phase 3 7439-89-6 29936
2
Acetylcysteine Approved, Investigational Phase 2, Phase 3 616-91-1 581 12035
3
Metformin Approved Phase 2, Phase 3 1115-70-4, 657-24-9 4091
4
Deferiprone Approved Phase 2, Phase 3 30652-11-0 2972
5
Curcumin Approved, Investigational Phase 3 458-37-7, 84765-67-3 969516
6
Bezafibrate Approved, Investigational Phase 2, Phase 3 41859-67-0 39042
7 Antiviral Agents Phase 2, Phase 3
8 Anti-Infective Agents Phase 2, Phase 3
9 Iron Chelating Agents Phase 2, Phase 3
10 Hormones Phase 2, Phase 3
11
Sitagliptin Phosphate Phase 2, Phase 3 654671-77-9
12 Hormone Antagonists Phase 2, Phase 3
13 Expectorants Phase 2, Phase 3
14 HIV Protease Inhibitors Phase 2, Phase 3
15 Antidotes Phase 2, Phase 3
16 Hypoglycemic Agents Phase 2, Phase 3
17 N-monoacetylcystine Phase 2, Phase 3
18 Respiratory System Agents Phase 2, Phase 3
19 Dipeptidyl-Peptidase IV Inhibitors Phase 2, Phase 3
20 Incretins Phase 2, Phase 3
21
protease inhibitors Phase 2, Phase 3
22 Chelating Agents Phase 2, Phase 3
23 Antirheumatic Agents Phase 3
24 Anti-Inflammatory Agents, Non-Steroidal Phase 3
25 Anti-Inflammatory Agents Phase 3
26 Analgesics, Non-Narcotic Phase 3
27 Analgesics Phase 3
28 Anti-Infective Agents, Local Phase 3
29 Antimetabolites Phase 2, Phase 3
30 Hypolipidemic Agents Phase 2, Phase 3
31 Lipid Regulating Agents Phase 2, Phase 3
32 Pharmaceutical Solutions Phase 3
33 Anesthetics Phase 3
34
Miconazole Approved, Investigational, Vet_approved Phase 2 22916-47-8 4189
35
Clotrimazole Approved, Vet_approved Phase 2 23593-75-1 2812
36
Dantrolene Approved, Investigational Phase 1, Phase 2 7261-97-4 6914273
37 Calcineurin Inhibitors Phase 2
38 Cyclosporins Phase 2
39 Antifungal Agents Phase 2
40 Immunosuppressive Agents Phase 2
41 Dermatologic Agents Phase 2
42 Immunologic Factors Phase 2
43
Epoetin Alfa Phase 1, Phase 2
44 Hematinics Phase 1, Phase 2
45 Ophthalmic Solutions Phase 2
46 Neuroprotective Agents Phase 1
47
Triamcinolone Approved, Vet_approved 124-94-7 31307
48
Tocopherol Approved, Investigational 1406-66-2
49
DL-alpha-Tocopherol Approved, Experimental, Investigational, Nutraceutical, Vet_approved 59-02-9, 10191-41-0 2116 14985
50
Tocotrienol Investigational 6829-55-6 9929901

Interventional clinical trials:

(show all 45)
# Name Status NCT ID Phase Drugs
1 External Natural History Controlled, Open-Label Intervention Study to Assess the Efficacy and Safety of Long-Term Treatment With Raxone® in Leber's Hereditary Optic Neuropathy (LHON) Completed NCT02774005 Phase 4 Idebenone
2 Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone, and Incretin Based Therapy Unknown status NCT02882477 Phase 2, Phase 3 Deferiprone;Acetylcysteine;Sitagliptin and Metformin
3 A Randomized, Double-blind, Placebo-controlled Trial of Curcumin in Leber's Hereditary Optic Neuropathy (LHON) Completed NCT00528151 Phase 3 curcumin
4 A Randomized, Double-Masked, Sham-Controlled Clinical Trial to Evaluate the Efficacy of a Single Intravitreal Injection of GS010 in Subjects Affected for 6 Months or Less by LHON Due to the G11778A Mutation in the Mitochondrial ND4 Gene Completed NCT02652767 Phase 3
5 Randomized, Double-Masked, Sham-Controlled Clinical Trial to Evaluate the Efficacy of a Single Intravitreal Injection of GS010 in Subjects Affected for More Than 6 Months and To 12 Months by LHON Due to the G11778A Mutation in the ND4 Gene Completed NCT02652780 Phase 3
6 Long-term Follow-up of ND4 LHON Subjects Treated With GS010 Ocular Gene Therapy in the RESCUE or REVERSE Phase III Clinical Trials (RESTORE) Completed NCT03406104 Phase 3
7 Study of Efficacy of Befizal® 200 mg for the Treatment of Leber Hereditary Optic Neuropathy Recruiting NCT04561466 Phase 2, Phase 3 Béfizal
8 A Phase 1/2/3, Multi-center, Two-part Clinical Trial to Evaluate the Safety and Efficacy of Gene Therapy for Leber's Hereditary Optic Neuropathy (LHON) Associated With ND4 Mutation Recruiting NCT04912843 Phase 2, Phase 3 NR082 injection
9 Efficacy and Safety of Bilateral Intravitreal Injection of GS010: A Randomized, Double-Masked, Placebo-Controlled Trial in Subjects Affected With G11778A ND4 Leber Hereditary Optic Neuropathy for Up to One Year Active, not recruiting NCT03293524 Phase 3 Placebo
10 A Single Intravitreal Injection of rAAV2-ND4 for the Treatment of Leber's Hereditary Optic Neuropathy Active, not recruiting NCT03153293 Phase 2, Phase 3 rAAV2-ND4
11 Study With Idebenone in Patients With Chronic Vision Loss Due to Leber's Hereditary Optic Neuropathy (LHON) Withdrawn NCT01495715 Phase 3 Idebenone;Placebo
12 Study the Safety and Efficacy of Bone Marrow Derived Autologous Cells for the Treatment of Optic Nerve Disease. It is Self Funded (Patients' Own Funding) Clinical Trial Unknown status NCT01834079 Phase 1, Phase 2
13 Trial of Cyclosporine in the Acute Phase of Leber Hereditary Optic Neuropathy Unknown status NCT02176733 Phase 2 cyclosporine
14 Systemic Erythropoietin Injection in Patients Having Optic Atrophy Completed NCT04680143 Phase 1, Phase 2 Systemic erythropoietin injection
15 An Open Label Dose Escalation Clinical Trial to Evaluate the Safety and the Tolerability of GS010 (rAAV2/2-ND4) in Patients With Leber Hereditary Optic Neuropathy Due to Mutations in the Mitochondrial NADH Dehydrogenase 4 Gene Completed NCT02064569 Phase 1, Phase 2
16 A Double-Blind, Randomised, Placebo-Controlled Study of the Efficacy, Safety and Tolerability of Idebenone in the Treatment of Patients With Leber's Hereditary Optic Neuropathy Completed NCT00747487 Phase 2 Idebenone;Placebo
17 A Prospective, Randomized, Double-Masked, Vehicle Controlled, Phase 2 Clinical Study to Evaluate the Safety, Tolerability and Efficacy of Elamipretide Topical Ophthalmic Solution in Subjects With Leber's Hereditary Optic Neuropathy (LHON) Completed NCT02693119 Phase 2 elamipretide (MTP-131) 1% topical ophthalmic solution;Vehicle topical ophthalmic solution
18 A Phase 1b/2a Trial of Dantrolene Sodium in Pediatric and Adult Patients With Wolfram Syndrome Active, not recruiting NCT02829268 Phase 1, Phase 2 dantrolene sodium
19 Near-infrared Light-emitting Diode (NIR-LED) Therapy for Leber's Hereditary Optic Neuropathy (LHON) Terminated NCT01389817 Phase 1, Phase 2
20 A Phase I Open-Label, Dose Escalation Trial of QPI-1007 Delivered by a Single Intravitreal Injection to Patients With Optic Nerve Atrophy (Stratum I) and Acute Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) (Stratum II) Completed NCT01064505 Phase 1 QPI-1007 at various doses
21 Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for the Treatment of Eye Diseases Recruiting NCT05147701 Phase 1
22 An Open-label Dose Escalation Study of an Adeno-associated Virus Vector (scAAV2-P1ND4v2) for Gene Therapy of Leber's Hereditary Optic Neuropathy (LHON) Caused by the G11778A Mutation in Mitochondrial DNA Active, not recruiting NCT02161380 Phase 1 injection of scAAV2-P1ND4v2 1.18x10e9 vg (Low),;injection of scAAV2-P1ND4v2 5.81 X10e9 vg (Med);injection of scAAV2-P1ND4v2 2.4 X10e10vg (High);injection of scAAV2-P1ND4v2 1.0 X10e11vg (Higher)
23 Cross Sectional Study of Autosomal Dominant Opticus Atrophy Unknown status NCT01522638
24 Expression of Optic Atrophy Type 1 (OPA1) Protein in Lung Adenocarcinoma Unknown status NCT01249053
25 Efficacy Study of Gene Therapy for The Treatment of Acute LHON Onset Within Three Months Unknown status NCT03428178 rAAV2-ND4
26 Transcorneal Electrical Stimulation Therapy for Retinal Disease - A Randomized, Single-blind Pilot Study Completed NCT00804102
27 A Prospective, Multicenter, Blinded Reading, Self Controlled, Superiority Priority Clinical Trial of Assisted Fundus Image Diagnosis Software for the Diagnosis of Multiple Eye Fundus Diseases Completed NCT04723160
28 Observational Registry Study of Leber Hereditary Optic Neuropathy (LHON) Affected Patients Completed NCT03295071
29 Leber Hereditary Optic Neuropathy (LHON) Historical Case Record Survey Completed NCT01892943
30 Historical Case Record Survey of Visual Acuity Data From Patients With Leber's Hereditary Optic Neuropathy (LHON) Completed NCT02796274
31 A Non-interventional Study of Clinical Experience in Patients Prescribed Raxone® for the Treatment of Leber's Hereditary Optic Neuropathy (LHON) Completed NCT02771379 Idebenone
32 New Methods of Dynamic Pupillometrics in Subjects With Visual and Color Vision Pathologies for the Detection, Functional Diagnosis and Follow-up of These Pathologies Completed NCT04909398
33 Safety and Efficacy Study of a Single Intravitreal Injection of rAAV2-ND4 Treatment of Leber Hereditary Optic Neuropathy Completed NCT01267422 rAAV2-ND4
34 A Single Visit, Observational, Follow-up Study of Patients With Leber's Hereditary Optic Neuropathy Following Participation in SNT-II-003 Trial Completed NCT01421381
35 Coordination of Rare Diseases at Sanford Recruiting NCT01793168
36 Bone Marrow Derived Stem Cell Ophthalmology Treatment Study II Recruiting NCT03011541
37 A Natural History Study of Neurodegeneration and Optic Atrophy Caused by SLC25A46 Mutations in Pediatric and Adult Patients Recruiting NCT04594590
38 A Natural History Study of Neurodegeneration and Optic Atrophy Caused by Ferredoxin Reductase Mutations in Pediatric and Adult Patients Recruiting NCT04580979
39 Evaluation of Impact of Disease and Visual Disability on Quality of Life and Loss of Independence of Patients Living in France With Leber's Hereditary Optic Neuropathy (LHON) Through Qualitative and Quantitative Data Collection Recruiting NCT05555784
40 Phenotypes, Biomarkers and Pathophysiology in Spastic Ataxias Recruiting NCT04297891
41 Wolfram Syndrome and WFS1-related Disorders International Registry and Clinical Study Recruiting NCT02841553
42 New Non-invasive Modalities for Assessing Retinal Structure and Function:Preliminary Investigation Recruiting NCT03475173
43 EAP Single Patient: Safety of Bilateral Intravitreal Injection of GS010 in a Single Subject Affected With G11778A ND4 Leber Hereditary Optic Neuropathy Available NCT03672968
44 Expanded Access Program for Idebenone in Patients With Leber's Hereditary Optic Neuropathy Who Completed the LEROS Study Available NCT04381091 Idebenone 150 MG Oral Tablet
45 Emergency Administration of EPI-743 to a Single Patient With Leber's Hereditary Optic Neuropathy [LHON] No longer available NCT02300753 EPI-743

Search NIH Clinical Center for 3-Methylglutaconic Aciduria, Type Iii

Cochrane evidence based reviews: optic atrophy

Genetic Tests for 3-Methylglutaconic Aciduria, Type Iii

Genetic tests related to 3-Methylglutaconic Aciduria, Type Iii:

# Genetic test Affiliating Genes
1 Optic Atrophy 28
2 3-Methylglutaconic Aciduria Type 3 28 OPA3

Anatomical Context for 3-Methylglutaconic Aciduria, Type Iii

Organs/tissues related to 3-Methylglutaconic Aciduria, Type Iii:

MalaCards : Eye, Retina, Brain, Bone Marrow, Bone, Skeletal Muscle, Lung

Publications for 3-Methylglutaconic Aciduria, Type Iii

Articles related to 3-Methylglutaconic Aciduria, Type Iii:

(show top 50) (show all 5586)
# Title Authors PMID Year
1
Type III 3-methylglutaconic aciduria (optic atrophy plus syndrome, or Costeff optic atrophy syndrome): identification of the OPA3 gene and its founder mutation in Iraqi Jews. 53 62 24 57 5
11668429 2001
2
Atypical presentation of Costeff syndrome-severe psychomotor involvement and electrical status epilepticus during slow wave sleep. 62 24 57 5
26190011 2015
3
Costeff syndrome: clinical features and natural history. 62 24 57 5
25201222 2014
4
Costeff optic atrophy syndrome: new clinical case and novel molecular findings. 62 24 57 5
18985435 2008
5
3-Methylglutaconic aciduria type III in a non-Iraqi-Jewish kindred: clinical and molecular findings. 62 24 57 5
12126933 2002
6
A novel OPA3 mutation revealed by exome sequencing: an example of reverse phenotyping. 62 57 5
23700088 2013
7
3-Methylglutaconic aciduria in the Iraqi-Jewish 'optic atrophy plus' (Costeff) syndrome. 62 24 57
7510656 1994
8
OPA3, mutated in 3-methylglutaconic aciduria type III, encodes two transcripts targeted primarily to mitochondria. 53 62 5
20350831 2010
9
OPA3 mutation screening in patients with unexplained 3-methylglutaconic aciduria. 53 62 5
15902555 2005
10
Iraqi-Jewish kindreds with optic atrophy plus (3-methylglutaconic aciduria type 3) demonstrate linkage disequilibrium with the CTG repeat in the 3' untranslated region of the myotonic dystrophy protein kinase gene. 53 62 57
9097959 1997
11
ATPase Domain AFG3L2 Mutations Alter OPA1 Processing and Cause Optic Neuropathy. 62 5
32219868 2020
12
MECR Mutations Cause Childhood-Onset Dystonia and Optic Atrophy, a Mitochondrial Fatty Acid Synthesis Disorder. 62 5
27817865 2016
13
Clinical and molecular genetic findings in autosomal dominant OPA3-related optic neuropathy. 62 5
25159689 2015
14
A novel heterozygous OPA3 mutation located in the mitochondrial target sequence results in altered steady-state levels and fragmented mitochondrial network. 62 5
24136862 2013
15
OPA3 gene mutations responsible for autosomal dominant optic atrophy and cataract. 62 5
15342707 2004
16
Behr's syndrome and 3-methylglutaconic aciduria. 62 57
1384336 1992
17
3-Methylglutaconic aciduria: a marker for as yet unspecified disorders and the relevance of prenatal diagnosis in a 'new' type ('type 4'). 62 57
1382150 1992
18
A familial syndrome of infantile optic atrophy, movement disorder, and spastic paraplegia. 62 57
2494568 1989
19
Whole-genome sequencing of patients with rare diseases in a national health system. 5
32581362 2020
20
Novel homozygous OPA3 mutation in an Afghani family with 3-methylglutaconic aciduria type III and optic atrophy. 62 24
31928268 2019
21
HTRA2 Defect: A Recognizable Inborn Error of Metabolism with 3-Methylglutaconic Aciduria as Discriminating Feature Characterized by Neonatal Movement Disorder and Epilepsy-Report of 11 Patients. 62 24
30114719 2018
22
Optic atrophy, cataracts, lipodystrophy/lipoatrophy, and peripheral neuropathy caused by a de novo OPA3 mutation. 62 24
28050599 2017
23
The neuropsychological profile of patients with 3-methylglutaconic aciduria type III, Costeff syndrome. 62 24
25657044 2015
24
Two novel compound heterozygous mutations in OPA3 in two siblings with OPA3-related 3-methylglutaconic aciduria. 62 24
24749080 2014
25
Inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature: proper classification and nomenclature. 62 24
23296368 2013
26
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. 5
17576681 2007
27
Musculoskeletal deformities in Behr syndrome. 62 24
11433166 2001
28
Statistical features of human exons and their flanking regions. 5
9536098 1998
29
Behr syndrome. 57
7538304 1995
30
The Human Gene Mutation Database (HGMD®): optimizing its use in a clinical diagnostic or research setting. 24
32596782 2020
31
Genetic etiologies of the electrical status epilepticus during slow wave sleep: systematic review. 24
29976148 2018
32
Parental influence on human germline de novo mutations in 1,548 trios from Iceland. 24
28959963 2017
33
3-Methylglutaconic aciduria--lessons from 50 genes and 977 patients. 24
23355087 2013
34
Phenotypic spectrum of MFN2 mutations in the Spanish population. 53 62
19889647 2010
35
OPA1-associated disorders: phenotypes and pathophysiology. 53 62
19389487 2009
36
OPA1-related dominant optic atrophy is not strongly influenced by mitochondrial DNA background. 53 62
19619285 2009
37
Acute and late-onset optic atrophy due to a novel OPA1 mutation leading to a mitochondrial coupling defect. 53 62
19325939 2009
38
Sporadic bilateral optic neuropathy in children: the role of mitochondrial abnormalities. 53 62
18676632 2008
39
Two Spanish families with Charcot-Marie-Tooth type 2A: clinical, electrophysiological and molecular findings. 53 62
18996695 2008
40
Mutated mitofusin 2 presents with intrafamilial variability and brain mitochondrial dysfunction. 53 62
18946002 2008
41
A novel deletion in the GTPase domain of OPA1 causes defects in mitochondrial morphology and distribution, but not in function. 53 62
18678599 2008
42
Association study of the effect of WFS1 polymorphisms on risk of type 2 diabetes in Japanese population. 53 62
19258739 2008
43
Autoimmune disease in a DFNA6/14/38 family carrying a novel missense mutation in WFS1. 53 62
18688868 2008
44
Autosomal dominant transmission of diabetes and congenital hearing impairment secondary to a missense mutation in the WFS1 gene. 53 62
18544103 2008
45
Testing of diabetes-associated WFS1 polymorphisms in the Diabetes Prevention Program. 53 62
18060660 2008
46
OPA1 mutations induce mitochondrial DNA instability and optic atrophy 'plus' phenotypes. 53 62
18158317 2008
47
A missense mutation in the murine Opa3 gene models human Costeff syndrome. 53 62
18222992 2008
48
The molecular mechanisms of OPA1-mediated optic atrophy in Drosophila model and prospects for antioxidant treatment. 53 62
18193945 2008
49
Sodium-potassium ATPase 1 subunit is a molecular partner of Wolframin, an endoplasmic reticulum protein involved in ER stress. 53 62
17947299 2008
50
A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. 53 62
17846994 2007

Variations for 3-Methylglutaconic Aciduria, Type Iii

ClinVar genetic disease variations for 3-Methylglutaconic Aciduria, Type Iii:

5 (show top 50) (show all 428)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PMPCA NM_015160.3(PMPCA):c.1066G>A (p.Gly356Ser) SNV Pathogenic
221553 rs768643552 GRCh37: 9:139313082-139313082
GRCh38: 9:136418630-136418630
2 PMPCA NM_015160.3(PMPCA):c.1129G>A (p.Ala377Thr) SNV Pathogenic
221552 rs753611141 GRCh37: 9:139313299-139313299
GRCh38: 9:136418847-136418847
3 overlap with 8 genes GRCh37/hg19 1q21.1-21.2(chr1:146618988-147824207) CN GAIN Pathogenic
523244 GRCh37: 1:146618988-147824207
GRCh38:
4 AFG3L2 NM_006796.3(AFG3L2):c.1541C>T (p.Pro514Leu) SNV Pathogenic
973106 rs1908300748 GRCh37: 18:12351095-12351095
GRCh38: 18:12351096-12351096
5 AFG3L2 NM_006796.3(AFG3L2):c.1289C>T (p.Thr430Ile) SNV Pathogenic
973108 rs1908369114 GRCh37: 18:12353033-12353033
GRCh38: 18:12353034-12353034
6 AFG3L2 NM_006796.3(AFG3L2):c.1036C>T (p.Leu346Phe) SNV Pathogenic
973109 rs755893615 GRCh37: 18:12356821-12356821
GRCh38: 18:12356822-12356822
7 AFG3L2 NM_006796.3(AFG3L2):c.1130T>C (p.Phe377Ser) SNV Pathogenic
973110 rs1908507433 GRCh37: 18:12356727-12356727
GRCh38: 18:12356728-12356728
8 AFG3L2 NM_006796.3(AFG3L2):c.1901_1902del (p.Val633_Ser634insTer) MICROSAT Pathogenic
973111 rs1907906060 GRCh37: 18:12340278-12340279
GRCh38: 18:12340279-12340280
9 AFG3L2 NM_006796.3(AFG3L2):c.1402C>T (p.Arg468Cys) SNV Pathogenic
565275 rs1020764190 GRCh37: 18:12351329-12351329
GRCh38: 18:12351330-12351330
10 OPA3 NM_025136.4(OPA3):c.32T>A (p.Leu11Gln) SNV Pathogenic
918005 rs1969907819 GRCh37: 19:46087991-46087991
GRCh38: 19:45584733-45584733
11 OPA3 NM_025136.4(OPA3):c.52C>T (p.Gln18Ter) SNV Pathogenic
Likely Pathogenic
620409 rs1568413644 GRCh37: 19:46087971-46087971
GRCh38: 19:45584713-45584713
12 OPA1 NM_130837.3(OPA1):c.2362C>T (p.Arg788Ter) SNV Pathogenic
431941 rs1553784985 GRCh37: 3:193376706-193376706
GRCh38: 3:193658917-193658917
13 OPA3 NC_000019.10:g.(?_45584613)_(45584774_?)del DEL Pathogenic
831267 GRCh37: 19:46087871-46088032
GRCh38:
14 AFG3L2 NM_006796.3(AFG3L2):c.1220A>G (p.Asp407Gly) SNV Pathogenic
973105 rs1908371616 GRCh37: 18:12353102-12353102
GRCh38: 18:12353103-12353103
15 OPA3 NM_025136.4(OPA3):c.143-2_143-1delinsCC INDEL Pathogenic
952107 rs1969382362 GRCh37: 19:46057170-46057171
GRCh38: 19:45553912-45553913
16 OPA3 NM_025136.4(OPA3):c.322_339del (p.Gln108_Glu113del) DEL Pathogenic
4242 rs80356526 GRCh37: 19:46056973-46056990
GRCh38: 19:45553715-45553732
17 AFG3L2 NM_006796.3(AFG3L2):c.1385C>T (p.Ala462Val) SNV Pathogenic
546814 rs912546325 GRCh37: 18:12351346-12351346
GRCh38: 18:12351347-12351347
18 AFG3L2 NM_006796.3(AFG3L2):c.1385C>T (p.Ala462Val) SNV Pathogenic
973107 rs912546325 GRCh37: 18:12351346-12351346
GRCh38: 18:12351347-12351347
19 AFG3L2 NM_006796.3(AFG3L2):c.1064C>T (p.Thr355Met) SNV Pathogenic
385335 rs1057522195 GRCh37: 18:12356793-12356793
GRCh38: 18:12356794-12356794
20 OPA3 NM_025136.4(OPA3):c.143-1G>C SNV Pathogenic
Pathogenic
4239 rs80356523 GRCh37: 19:46057170-46057170
GRCh38: 19:45553912-45553912
21 OPA3 NM_025136.4(OPA3):c.313C>G (p.Gln105Glu) SNV Pathogenic
4241 rs80356525 GRCh37: 19:46056999-46056999
GRCh38: 19:45553741-45553741
22 AFG3L2 NM_006796.3(AFG3L2):c.1394G>A (p.Arg465Lys) SNV Pathogenic
973104 rs1908309088 GRCh37: 18:12351337-12351337
GRCh38: 18:12351338-12351338
23 AFG3L2, TUBB6 NM_006796.3(AFG3L2):c.2375dup (p.Gly792_Glu793insTer) DUP Pathogenic
973112 rs1907449398 GRCh37: 18:12329582-12329583
GRCh38: 18:12329583-12329584
24 OPA3 NM_025136.4(OPA3):c.143-1G>A SNV Pathogenic
1727235 GRCh37: 19:46057170-46057170
GRCh38: 19:45553912-45553912
25 OPA3 NC_000019.9:g.(46057170_46087880)_(46088123_?)del DEL Likely Pathogenic
1723421 GRCh37: 19:46057170-46088123
GRCh38:
26 ISCA2 NM_194279.4(ISCA2):c.229G>A (p.Gly77Ser) SNV Likely Pathogenic
183353 rs730882246 GRCh37: 14:74961032-74961032
GRCh38: 14:74494329-74494329
27 OPA3 NM_025136.4(OPA3):c.415C>T (p.Gln139Ter) SNV Likely Pathogenic
21710 rs28937899 GRCh37: 19:46056897-46056897
GRCh38: 19:45553639-45553639
28 OPA3 NC_000019.10:g.(?_45553504)_(45553921_?)del DEL Likely Pathogenic
830708 GRCh37: 19:46056762-46057179
GRCh38:
29 OPA3 NM_025136.4(OPA3):c.142+5G>C SNV Likely Pathogenic
Uncertain Significance
553096 rs1250409781 GRCh37: 19:46087876-46087876
GRCh38: 19:45584618-45584618
30 MECR NM_016011.5(MECR):c.855T>G (p.Tyr285Ter) SNV Likely Pathogenic
374879 rs1057519286 GRCh37: 1:29522746-29522746
GRCh38: 1:29196234-29196234
31 MECR NM_016011.5(MECR):c.830+2dup DUP Likely Pathogenic
449055 rs756421370 GRCh37: 1:29527026-29527026
GRCh38: 1:29200513-29200514
32 overlap with 4 genes NC_000002.11:g.15744252_17675820del DEL Likely Pathogenic
812922 GRCh37: 2:15744252-17675820
GRCh38:
33 MECR NM_016011.5(MECR):c.695G>A (p.Gly232Glu) SNV Likely Pathogenic
374878 rs762913101 GRCh37: 1:29528516-29528516
GRCh38: 1:29202004-29202004
34 OPA1 NM_130837.3(OPA1):c.2051C>G (p.Ser684Ter) SNV Likely Pathogenic
1691850 GRCh37: 3:193372689-193372689
GRCh38: 3:193654900-193654900
35 OPA3 NM_025136.4(OPA3):c.206_258del (p.Lys69fs) DEL Likely Pathogenic
1066277 GRCh37: 19:46057054-46057106
GRCh38: 19:45553796-45553848
36 OPA3 NM_025136.4(OPA3):c.1A>G (p.Met1Val) SNV Likely Pathogenic
1067581 GRCh37: 19:46088022-46088022
GRCh38: 19:45584764-45584764
37 OPA3 NM_025136.4(OPA3):c.217dup (p.Glu73fs) DUP Likely Pathogenic
554806 rs1555732963 GRCh37: 19:46057094-46057095
GRCh38: 19:45553836-45553837
38 OPA3 NM_025136.4(OPA3):c.61A>T (p.Lys21Ter) SNV Likely Pathogenic
555674 rs1555736814 GRCh37: 19:46087962-46087962
GRCh38: 19:45584704-45584704
39 OPA3 NM_025136.4(OPA3):c.142+1G>A SNV Likely Pathogenic
552448 rs1555736793 GRCh37: 19:46087880-46087880
GRCh38: 19:45584622-45584622
40 OPA3 NM_025136.4(OPA3):c.100dup (p.Ser34fs) DUP Likely Pathogenic
557484 rs1555736803 GRCh37: 19:46087922-46087923
GRCh38: 19:45584664-45584665
41 OPA3 NM_025136.4(OPA3):c.539A>G (p.Ter180Trp) SNV Likely Pathogenic
370448 rs1057516497 GRCh37: 19:46056773-46056773
GRCh38: 19:45553515-45553515
42 OAT NM_000274.4(OAT):c.875A>G (p.Lys292Arg) SNV Likely Pathogenic
374146 rs1057518927 GRCh37: 10:126091521-126091521
GRCh38: 10:124402952-124402952
43 PIGQ NM_004204.5(PIGQ):c.619C>T (p.Arg207Ter) SNV Likely Pathogenic
183339 rs730882240 GRCh37: 16:624693-624693
GRCh38: 16:574693-574693
44 MECR NM_016011.5(MECR):c.854A>G (p.Tyr285Cys) SNV Likely Pathogenic
374881 rs759218713 GRCh37: 1:29522747-29522747
GRCh38: 1:29196235-29196235
45 MECR NM_016011.4(MECR):c.772C>T (p.Arg258Trp) SNV Likely Pathogenic
374882 rs145192716 GRCh37: 1:29527086-29527086
GRCh38: 1:29200574-29200574
46 MECR NM_016011.5(MECR):c.247_250del (p.Asn83fs) DEL Likely Pathogenic
374883 rs1057519287 GRCh37: 1:29543124-29543127
GRCh38: 1:29216612-29216615
47 OPA3 NM_025136.4(OPA3):c.254G>A (p.Gly85Asp) SNV Likely Pathogenic
807645 rs1599964721 GRCh37: 19:46057058-46057058
GRCh38: 19:45553800-45553800
48 OPA3 NM_025136.4(OPA3):c.*4696ATAA[8] MICROSAT Conflicting Interpretations Of Pathogenicity
329598 rs58537694 GRCh37: 19:46052048-46052049
GRCh38: 19:45548790-45548791
49 OPA3 NM_025136.4(OPA3):c.*80G>T SNV Uncertain Significance
329683 rs540023428 GRCh37: 19:46056692-46056692
GRCh38: 19:45553434-45553434
50 OPA3 NM_025136.4(OPA3):c.*398G>T SNV Uncertain Significance
329676 rs183851663 GRCh37: 19:46056374-46056374
GRCh38: 19:45553116-45553116

Copy number variations for 3-Methylglutaconic Aciduria, Type Iii from CNVD:

6
# CNVD ID Chromosome Start End Type Gene Symbol CNVD Disease
1 173060 3 189400000 193800000 Deletion OPA1 Optic atrophy

Expression for 3-Methylglutaconic Aciduria, Type Iii

Search GEO for disease gene expression data for 3-Methylglutaconic Aciduria, Type Iii.

Pathways for 3-Methylglutaconic Aciduria, Type Iii

Pathways related to 3-Methylglutaconic Aciduria, Type Iii according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.41 WFS1 OPA1 MFN2 MFN1
2
Show member pathways
10.26 MFN2 MFN1

GO Terms for 3-Methylglutaconic Aciduria, Type Iii

Cellular components related to 3-Methylglutaconic Aciduria, Type Iii according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial matrix GO:0005759 9.81 PMPCA OAT MECR ISCA2 BTD
2 mitochondrion GO:0005739 9.7 TMEM126A PMPCA OPA3 OPA1 OAT MTRFR
3 obsolete intrinsic component of mitochondrial outer membrane GO:0031306 8.96 MFN2 MFN1

Biological processes related to 3-Methylglutaconic Aciduria, Type Iii according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 visual perception GO:0007601 9.92 WFS1 OPA3 OPA1 OAT
2 cristae formation GO:0042407 9.67 MICOS13 AFG3L2
3 GTP metabolic process GO:0046039 9.56 OPA1 MFN1
4 mitochondrion localization GO:0051646 9.46 MFN2 MFN1
5 mitochondrion organization GO:0007005 9.35 OPA1 MFN2 MFN1 AFG3L2
6 mitochondrial fusion GO:0008053 9.23 OPA1 MFN2 MFN1 AFG3L2

Sources for 3-Methylglutaconic Aciduria, Type Iii

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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