LS
MCID: LGH007
MIFTS: 69

Leigh Syndrome (LS)

Categories: Endocrine diseases, Eye diseases, Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases
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Aliases & Classifications for Leigh Syndrome

MalaCards integrated aliases for Leigh Syndrome:

Name: Leigh Syndrome 57 11 19 42 58 73 28 28 28 53 5 38 75 33
Leigh Disease 11 19 42 58 75 73 43 14 71 33
Leigh Syndrome Due to Mitochondrial Complex Iv Deficiency 73 28 5 16
Infantile Subacute Necrotizing Encephalopathy 19 42 58 33
Leigh Syndrome Due to Mitochondrial Complex I Deficiency 73 28 5
Leigh's Disease 19 42 52
Sne 57 19 73
Ls 57 19 73
Leigh Syndrome Due to Mitochondrial Complex Iii Deficiency 73 28
Necrotizing Encephalopathy, Infantile Subacute, of Leigh 57 71
Necrotizing Encephalopathy Infantile Subacute of Leigh 19 73
Subacute Necrotizing Encephalomyelopathy 11 42
Leigh Syndrome Due to Mitochondrial Complex Ii Deficiency 73
Leigh Syndrome Due to Mitochondrial Complex V Deficiency 73
Juvenile Subacute Necrotizing Encephalomyelopathy 11
Encephalopathy, Subacute Necrotizing, Infantile 71
Encephalopathy, Subacute Necrotizing, Juvenile 71
Juvenile Subacute Necrotizing Encephalopathy 42
Infantile Necrotizing Encephalomyelopathy 11
Subacute Necrotising Encephalomyelopathy 33
Subacute Necrotizing Encephalopathy 19
Maternally Inherited Leigh Syndrome 71
Subacute Necrotising Encephalopathy 33
Leigh's Necrotizing Encephalopathy 19

Characteristics:


Inheritance:

Autosomal recessive,Mitochondrial inheritance,X-linked recessive 58 , Autosomal recessive 57

Prevelance:

1-9/100000 (Europe, Australia, Europe) 58

Age Of Onset:

All ages 58

Age Of Death:

any age 58

OMIM®:

57 (Updated 24-Oct-2022)
Miscellaneous:
clinical heterogeneity
onset usually in infancy or early childhood
progressive disorder, usually with rapid, relentless course
genetic heterogeneity (may be caused by mutation in nuclear-encoded or mitochondrial-encoded genes)
subset of patients have cytochrome c oxidase deficiency (see )
see also x-linked leigh syndrome
see also french-canadian type of leigh syndrome


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Inborn errors of metabolism


Summaries for Leigh Syndrome

MedlinePlus Genetics: 42 Leigh syndrome is a severe neurological disorder that usually becomes apparent in the first year of life. This condition is characterized by progressive loss of mental and movement abilities (psychomotor regression) and typically results in death within two to three years, usually due to respiratory failure. A small number of individuals do not develop symptoms until adulthood or have symptoms that worsen more slowly.The first signs of Leigh syndrome seen in infancy are usually vomiting, diarrhea, and difficulty swallowing (dysphagia), which disrupts eating. These problems often result in an inability to grow and gain weight at the expected rate (failure to thrive). Severe muscle and movement problems are common in Leigh syndrome. Affected individuals may develop weak muscle tone (hypotonia), involuntary muscle contractions (dystonia), and problems with movement and balance (ataxia). Loss of sensation and weakness in the limbs (peripheral neuropathy), common in people with Leigh syndrome, may also make movement difficult.Several other features may occur in people with Leigh syndrome. Many individuals with this condition develop weakness or paralysis of the muscles that move the eyes (ophthalmoparesis); rapid, involuntary eye movements (nystagmus); or degeneration of the nerves that carry information from the eyes to the brain (optic atrophy). Severe breathing problems are common, and these problems can worsen until they cause acute respiratory failure. Some affected individuals develop hypertrophic cardiomyopathy, which is a thickening of the heart muscle that forces the heart to work harder to pump blood. In addition, a substance called lactate can build up in the body, and excessive amounts are often found in the blood, urine, or the fluid that surrounds and protects the brain and spinal cord (cerebrospinal fluid) of people with Leigh syndrome.The signs and symptoms of Leigh syndrome are caused in part by patches of damaged tissue (lesions) that develop in the brains of people with this condition. A medical procedure called magnetic resonance imaging (MRI) reveals characteristic lesions in certain regions of the brain. These regions include the basal ganglia, which help control movement; the cerebellum, which controls the ability to balance and coordinates movement; and the brainstem, which connects the brain to the spinal cord and controls functions such as swallowing and breathing. The brain lesions are often accompanied by loss of the myelin coating around nerves (demyelination), which reduces the ability of the nerves to activate muscles used for movement or relay sensory information from the rest of the body back to the brain.

MalaCards based summary: Leigh Syndrome, also known as leigh disease, is related to mitochondrial dna-associated leigh syndrome and mitochondrial complex iv deficiency, nuclear type 5, and has symptoms including ataxia, muscle spasticity and ophthalmoplegia. An important gene associated with Leigh Syndrome is SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A), and among its related pathways/superpathways are Metabolism and "Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.". The drugs Cysteamine and Ubidecarenone have been mentioned in the context of this disorder. Affiliated tissues include spinal cord, eye and brain, and related phenotypes are increased serum lactate and increased csf lactate

NINDS: 52 Leigh's disease is a rare inherited neurometabolic disorder that affects the central nervous system. This progressive disorder begins in infants between the ages of three months and two years. Rarely, it occurs in teenagers and adults. Leigh's disease can be caused by mutations in mitochondrial DNA or by deficiencies of an enzyme called pyruvate dehydrogenase. Symptoms of Leigh's disease usually progress rapidly. The earliest signs may be poor sucking ability,and the loss of head control and motor skills.These symptoms may be accompanied by loss of appetite, vomiting, irritability, continuous crying, and seizures. As the disorder progresses, symptoms may also include generalized weakness, lack of muscle tone, and episodes of lactic acidosis, which can lead to impairment of respiratory and kidney function.   In Leigh’s disease, genetic mutations in mitochondrial DNA interfere with the energy sources that run cells in an area of the brain that plays a role in motor movements. The primary function of mitochondria is to convert the energy in glucose and fatty acids into a substance called adenosine triphosphate ( ATP). The energy in ATP drives virtually all of a cell's metabolic functions. Genetic mutations in mitochondrial DNA, therefore, result in a chronic lack of energy in these cells, which in turn affects the central nervous system and causes progressive degeneration of motor functions. There is also a form of Leigh’s disease (called X-linked Leigh's disease) which is the result of mutations in a gene that produces another group of substances that are important for cell metabolism. This gene is only found on the X chromosome.

GARD: 19 Leigh syndrome is a rare, inherited neurodegenerative condition. It usually becomes apparent in infancy, often after a viral infection. Signs and symptoms usually progress rapidly. Early symptoms may include poor sucking ability; loss of head control and motor skills; loss of appetite; vomiting; and seizures. As the condition progresses, symptoms may include weakness and lack of muscle tone; spasticity; movement disorders; cerebellar ataxia; and peripheral neuropathy. Complications can lead to impairment of respiratory, heart and kidney function. The term "Leigh-like syndrome" is often used for people with features that are strongly suggestive of Leigh syndrome but who do not meet the diagnostic criteria. The inheritance of Leigh syndrome depends on where the responsible gene is located in each case. This is because it can be due to genetic changes in either mitochondrial DNA or nuclear DNA: Mitochondrial DNA-associated Leigh syndrome follows a mitochondrial inheritance pattern (also called maternal inheritance). Nuclear gene-encoded Leigh syndrome may be inherited in an autosomal recessive or X-linked manner.

OMIM®: 57 Leigh syndrome is a clinically and genetically heterogeneous disorder resulting from defective mitochondrial energy generation. It most commonly presents as a progressive and severe neurodegenerative disorder with onset within the first months or years of life, and may result in early death. Affected individuals usually show global developmental delay or developmental regression, hypotonia, ataxia, dystonia, and ophthalmologic abnormalities, such as nystagmus or optic atrophy. The neurologic features are associated with the classic findings of T2-weighted hyperintensities in the basal ganglia and/or brainstem on brain imaging. Leigh syndrome can also have detrimental multisystemic affects on the cardiac, hepatic, gastrointestinal, and renal organs. Biochemical studies in patients with Leigh syndrome tend to show increased lactate and abnormalities of mitochondrial oxidative phosphorylation (summary by Lake et al., 2015). (256000) (Updated 24-Oct-2022)

UniProtKB/Swiss-Prot: 73 An early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions in one or more areas of the central nervous system including the brainstem, thalamus, basal ganglia, cerebellum and spinal cord. Clinical features depend on which areas of the central nervous system are involved and include subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, and dysphagia.

Disease Ontology: 11 A mitochondrial metabolism disease characterized by progressive loss of mental and movement abilities. Symptoms usually begin between ages of three months and two years and include loss of appetite, vomiting, irritability and seizure activity.

Orphanet: 58 A progressive neurological disease defined by specific neuropathological features associating brainstem and basal ganglia lesions.

Wikipedia: 75 Leigh syndrome (also called Leigh disease and subacute necrotizing encephalomyelopathy) is an inherited... more...

Related Diseases for Leigh Syndrome

Diseases related to Leigh Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 429)
# Related Disease Score Top Affiliating Genes
1 mitochondrial dna-associated leigh syndrome 33.6 MT-TW MT-ND6 MT-ND5 MT-ND3 MT-ND2 MT-ND1
2 mitochondrial complex iv deficiency, nuclear type 5 33.5 SURF1 MT-ND6 MT-ATP6 BCS1L
3 mitochondrial complex i deficiency, nuclear type 1 33.5 SURF1 SDHA NDUFV1 NDUFS4 NDUFAF6 NDUFAF5
4 mitochondrial complex iv deficiency, nuclear type 1 33.1 SURF1 NDUFV1 NDUFAF6 COX15 BCS1L
5 mitochondrial dna-associated leigh syndrome and narp 33.0 MT-ND3 MT-ATP6
6 leigh syndrome with leukodystrophy 32.8 SURF1 SDHA NDUFV1 NDUFS4 NDUFAF6 NDUFAF5
7 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes 32.7 SURF1 NDUFS4 MT-TW MT-ND6 MT-ND5 MT-ND3
8 mitochondrial complex i deficiency, nuclear type 16 32.4 NDUFAF5 MT-ND6 MT-ND3 MT-ND1 MT-ATP6
9 mitochondrial disease 32.3 SURF1 NDUFS4 MT-ND6 MT-ND5 MT-ND3 MT-ND1
10 lactic acidosis 32.1 SURF1 NDUFV1 NDUFS4 MT-ND6 MT-ND5 MT-ND3
11 leber hereditary optic neuropathy, modifier of 31.8 SURF1 SDHA NDUFV1 NDUFS4 NDUFAF5 NDUFAF2
12 kearns-sayre syndrome 31.8 SURF1 SDHA NDUFV1 NDUFS4 MT-ND6 MT-ND5
13 3-methylglutaconic aciduria, type iii 31.7 SDHA MT-ND6 MT-ND2 MT-ND1 MT-ATP6 COX15
14 neuropathy 31.7 MT-ND6 MT-ND5 MT-ND3 MT-ND2 MT-ND1 MT-ATP6
15 mitochondrial encephalomyopathy 31.6 SURF1 NDUFV1 NDUFS4 MT-TW MT-ND6 MT-ND5
16 optic nerve disease 31.6 SURF1 NDUFS4 MT-ND6 MT-ND5 MT-ND3 MT-ND2
17 retinitis pigmentosa 31.6 SURF1 MT-TW MT-ND6 MT-ND3 MT-ND2 MT-ND1
18 myopathy 31.6 SDHA NDUFV1 NDUFS4 NDUFAF6 NDUFAF5 NDUFAF2
19 neuropathy, ataxia, and retinitis pigmentosa 31.6 SURF1 NDUFS4 MT-ND6 MT-ATP6 COX15
20 leukodystrophy 31.5 SURF1 SDHA NDUFV1 NDUFS4 NDUFAF6 NDUFAF5
21 mitochondrial myopathy 31.5 SURF1 SDHA NDUFS4 MT-TW MT-ND6 MT-ND5
22 hereditary optic neuropathy 31.4 MT-ND6 MT-ND5 MT-ND3 MT-ND2 MT-ATP6
23 myoclonic epilepsy associated with ragged-red fibers 31.4 SURF1 MT-ND6 MT-ND5 MT-ND3 MT-ND2 MT-ND1
24 early myoclonic encephalopathy 31.4 NDUFV1 NDUFS4 MT-ND6 MT-ND5 MT-ND3 MT-ND2
25 leber plus disease 31.0 NDUFS4 NDUFAF5 MT-ND6 MT-ND5 MT-ND3 MT-ND2
26 cortical blindness 31.0 MT-ND6 MT-ND5 MT-ND1
27 charcot-marie-tooth disease, type 4k 30.9 SURF1 NDUFAF6 NDUFAF5 FOXRED1 COX15
28 cardiomyopathy, infantile hypertrophic 30.7 SURF1 MTFMT MT-ND6 MT-ATP6 COX15
29 chronic progressive external ophthalmoplegia 30.7 SURF1 MT-ND6 MT-ND3 MT-ND1 MT-ATP6
30 leber optic atrophy and dystonia 30.6 MT-ND6 MT-ND5 MT-ND3 MT-ND1
31 scotoma 30.3 MT-ND6 MT-ND1
32 congenital lactic acidosis, saguenay-lac-saint-jean type 11.4
33 pyruvate carboxylase deficiency 11.4
34 3-methylglutaconic aciduria with deafness, encephalopathy, and leigh-like syndrome 11.2
35 mitochondrial complex v deficiency, nuclear type 5 11.2
36 mitochondrial complex ii deficiency, nuclear type 2 11.2
37 nuclear gene-encoded leigh syndrome spectrum 11.2
38 mitochondrial complex ii deficiency, nuclear type 1 11.1
39 mitochondrial complex iii deficiency, nuclear type 2 11.1
40 combined oxidative phosphorylation deficiency 24 11.1
41 mitochondrial complex i deficiency, nuclear type 36 11.1
42 isolated cytochrome c oxidase deficiency 11.1
43 mitochondrial complex iv deficiency, nuclear type 2 11.1
44 coenzyme q10 deficiency, primary, 1 11.1
45 combined oxidative phosphorylation deficiency 15 11.1
46 mitochondrial complex v deficiency, nuclear type 6 11.1
47 sulfide:quinone oxidoreductase deficiency 11.1
48 nuclear gene-encoded leigh syndrome 11.1
49 necrotizing encephalomyelopathy, subacute, of leigh, adult 11.1
50 leigh syndrome with nephrotic syndrome 11.0

Graphical network of the top 20 diseases related to Leigh Syndrome:



Diseases related to Leigh Syndrome

Symptoms & Phenotypes for Leigh Syndrome

Human phenotypes related to Leigh Syndrome:

58 30 (show top 50) (show all 114)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 increased serum lactate 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0002151
2 increased csf lactate 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0002490
3 lactic acidosis 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0003128
4 infantile muscular hypotonia 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0008947
5 lacticaciduria 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0003648
6 failure to thrive 58 30 Frequent (33%) Frequent (79-30%)
HP:0001508
7 developmental regression 58 30 Frequent (33%) Frequent (79-30%)
HP:0002376
8 sensorineural hearing impairment 58 30 Frequent (33%) Frequent (79-30%)
HP:0000407
9 optic atrophy 58 30 Frequent (33%) Frequent (79-30%)
HP:0000648
10 hypertrophic cardiomyopathy 58 30 Frequent (33%) Frequent (79-30%)
HP:0001639
11 ophthalmoplegia 58 30 Frequent (33%) Frequent (79-30%)
HP:0000602
12 decreased activity of mitochondrial complex i 58 30 Frequent (33%) Frequent (79-30%)
HP:0011923
13 leukodystrophy 58 30 Frequent (33%) Frequent (79-30%)
HP:0002415
14 focal t2 hyperintense brainstem lesion 58 30 Frequent (33%) Frequent (79-30%)
HP:0012748
15 feeding difficulties 58 30 Frequent (33%) Frequent (79-30%)
HP:0011968
16 progressive neurologic deterioration 58 30 Frequent (33%) Frequent (79-30%)
HP:0002344
17 hypertrichosis 58 30 Frequent (33%) Frequent (79-30%)
HP:0000998
18 abnormal thalamic mri signal intensity 58 30 Frequent (33%) Frequent (79-30%)
HP:0012696
19 severe viral infection 58 30 Frequent (33%) Frequent (79-30%)
HP:0031691
20 gliosis 58 30 Frequent (33%) Frequent (79-30%)
HP:0002171
21 diffuse spongiform leukoencephalopathy 58 30 Frequent (33%) Frequent (79-30%)
HP:0006943
22 focal t2 hyperintense basal ganglia lesion 58 30 Frequent (33%) Frequent (79-30%)
HP:0007183
23 decreased activity of the pyruvate dehydrogenase complex 58 30 Frequent (33%) Frequent (79-30%)
HP:0002928
24 elevated brain lactate level by mrs 58 30 Frequent (33%) Frequent (79-30%)
HP:0012707
25 complex organic aciduria 58 30 Frequent (33%) Frequent (79-30%)
HP:0008336
26 global developmental delay 30 Frequent (33%) HP:0001263
27 abnormal dentate nucleus morphology 30 Frequent (33%) HP:0100321
28 agenesis of corpus callosum 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001274
29 ptosis 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000508
30 nystagmus 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000639
31 ataxia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001251
32 dysphagia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002015
33 myopathy 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0003198
34 hypoglycemia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001943
35 anemia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001903
36 skeletal muscle atrophy 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0003202
37 congestive heart failure 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001635
38 multiple joint contractures 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002828
39 abnormality of extrapyramidal motor function 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002071
40 dystonia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001332
41 hepatic failure 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001399
42 respiratory failure 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002878
43 distal muscle weakness 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002460
44 abnormal pattern of respiration 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002793
45 choreoathetosis 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001266
46 methylmalonic aciduria 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0012120
47 spastic diplegia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001264
48 hypoplasia of the corpus callosum 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002079
49 hyperalaninemia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0003348
50 ketoacidosis 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001993

Symptoms via clinical synopsis from OMIM®:

57 (Updated 24-Oct-2022)
Neurologic Central Nervous System:
seizures
spasticity
hyperreflexia
ataxia
dysarthria
more
Head And Neck Eyes:
ptosis
nystagmus
optic atrophy
strabismus
ophthalmoplegia
more
Laboratory Abnormalities:
increased serum lactate
increased csf lactate

Metabolic Features:
lactic acidosis

Muscle Soft Tissue:
hypotonia

Growth Other:
failure to thrive

Neurologic Behavioral Psychiatric Manifestations:
emotional lability

Respiratory:
respiratory failure
abnormal respiratory patterns

Skin Nails Hair Hair:
hypertrichosis

Clinical features from OMIM®:

256000 (Updated 24-Oct-2022)

UMLS symptoms related to Leigh Syndrome:


ataxia; muscle spasticity; ophthalmoplegia; seizures

Drugs & Therapeutics for Leigh Syndrome

Drugs for Leigh Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 9)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Cysteamine Approved, Investigational Phase 2 60-23-1 6058
2
Ubidecarenone Approved, Investigational, Nutraceutical Phase 2 303-98-0 5281915
3 Ubiquinone Phase 2
4 Micronutrients Phase 2
5 Trace Elements Phase 2
6 Pharmaceutical Solutions Phase 2
7 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid Phase 1
8 Protective Agents Phase 1
9 Antioxidants Phase 1

Interventional clinical trials:

(show all 13)
# Name Status NCT ID Phase Drugs
1 Efficacy and Safety Study of Vatiquinone for the Treatment of Mitochondrial Disease Subjects With Refractory Epilepsy Recruiting NCT04378075 Phase 2, Phase 3 Vatiquinone
2 A Phase 2B Randomized, Placebo Controlled, Double Blind Clinical Trial of EPI-743 in Children With Leigh Syndrome Completed NCT01721733 Phase 2 Placebo;EPI-743 15 mg/kg;EPI-743 5 mg/kg
3 An Open-Label, Dose-Escalating Study to Assess the Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of Cysteamine Bitartrate Delayed-release Capsules (RP103) for Treatment of Children With Inherited Mitochondrial Disease Completed NCT02023866 Phase 2 Cysteamine Bitartrate
4 A Randomized Placebo Controlled, Double-blind Phase II Study to Explore the Safety, Efficacy and Pharmacokinetics of Sonlicromanol in Children With Genetically Confirmed Mitochondrial Disease Recruiting NCT04846036 Phase 2 Sonlicromanol;Placebo
5 Long-Term Safety and Efficacy Evaluation of Vatiquinone (EPI-743) in Children With Leigh Syndrome Active, not recruiting NCT02352896 Phase 2 EPI-743
6 A Phase 2a, Open-label Study to Evaluate the Safety, Tolerability, and Clinical Activity of ABI-009 (Nab-sirolimus) in Patients With Genetically-confirmed Leigh or Leigh-like Syndrome Withdrawn NCT03747328 Phase 2 ABI-009
7 A Phase I, Randomized, Double Blind, Placebo-controlled, Dose-escalating Clinical Trial With KH176 Completed NCT02544217 Phase 1 KH176;placebo
8 Coordination of Rare Diseases at Sanford Recruiting NCT01793168
9 The International Registry for Leigh Syndrome Recruiting NCT03137355
10 Global Mitochondrial Registry to Define Natural History and Outcome Measures to Achieve Definite Trial Readiness for Mitochondrial Disorders Recruiting NCT05554835
11 The NIH Mini Study: Metabolism, INfection and Immunity in Inborn Errors of Mitochondrial Metabolism Recruiting NCT01780168
12 Tissue Study for Mitochondrial Disorders Enrolling by invitation NCT01803906
13 A Natural History Study of Surfeit Locus Protein 1 (SURF1)-Associated Leigh Syndrome Withdrawn NCT05277363

Search NIH Clinical Center for Leigh Syndrome

Cochrane evidence based reviews: leigh disease

Genetic Tests for Leigh Syndrome

Genetic tests related to Leigh Syndrome:

# Genetic test Affiliating Genes
1 Leigh Syndrome (nuclear Dna Mutation) 28
2 Leigh Syndrome 28
3 Leigh Syndrome Due to Mitochondrial Complex I Deficiency 28
4 Leigh Syndrome (mtdna Mutation) 28
5 Leigh Syndrome Due to Mitochondrial Complex Iii Deficiency 28
6 Leigh Syndrome Due to Mitochondrial Complex Iv Deficiency 28

Anatomical Context for Leigh Syndrome

Organs/tissues related to Leigh Syndrome:

MalaCards : Spinal Cord, Eye, Brain, Thalamus, Cerebellum, Heart, Kidney

Publications for Leigh Syndrome

Articles related to Leigh Syndrome:

(show top 50) (show all 1649)
# Title Authors PMID Year
1
Leigh disease associated with a novel mitochondrial DNA ND5 mutation. 53 62 57 5
11938446 2002
2
Leigh syndrome caused by mitochondrial DNA G13513A mutation: frequency and clinical features in Japan. 62 57 5
14730434 2004
3
Leigh syndrome: clinical features and biochemical and DNA abnormalities. 62 57 5
8602753 1996
4
NDUFS4 mutations cause Leigh syndrome with predominant brainstem involvement. 53 62 5
19364667 2009
5
Light and electron microscopy characteristics of the muscle of patients with SURF1 gene mutations associated with Leigh disease. 53 62 5
17908801 2008
6
The G13513A mutation in the ND5 gene of mitochondrial DNA as a common cause of MELAS or Leigh syndrome: evidence from 12 cases. 53 62 5
18332249 2008
7
Variable phenotype including Leigh syndrome with a 9185T>C mutation in the MTATP6 gene. 53 62 5
18461509 2007
8
A novel mutation of the NDUFS7 gene leads to activation of a cryptic exon and impaired assembly of mitochondrial complex I in a patient with Leigh syndrome. 53 62 5
17604671 2007
9
A novel recurrent mitochondrial DNA mutation in ND3 gene is associated with isolated complex I deficiency causing Leigh syndrome and dystonia. 53 62 5
17152068 2007
10
Maternal segmental disomy in Leigh syndrome with cytochrome c oxidase deficiency caused by homozygous SURF1 mutation. 53 62 5
16773507 2006
11
Clinical and laboratory survey of 65 Chinese patients with Leigh syndrome. 53 62 5
16542579 2006
12
Retrospective, multicentric study of 180 children with cytochrome C oxidase deficiency. 53 62 5
16326995 2006
13
Two new mutations in the MTATP6 gene associated with Leigh syndrome. 53 62 5
16217706 2005
14
Unusual clinical presentations in four cases of Leigh disease, cytochrome C oxidase deficiency, and SURF1 gene mutations. 53 62 5
16225813 2005
15
Novel mutations in COX15 in a long surviving Leigh syndrome patient with cytochrome c oxidase deficiency. 53 62 5
15863660 2005
16
A new mitochondrial DNA mutation in ND3 gene causing severe Leigh syndrome with early lethality. 53 62 5
14764913 2004
17
Impaired complex I assembly in a Leigh syndrome patient with a novel missense mutation in the ND6 gene. 53 62 5
14595656 2003
18
SURF1 gene mutations in three cases with Leigh syndrome and cytochrome c oxidase deficiency. 53 62 5
14557577 2003
19
Leigh Syndrome with COX deficiency and SURF1 gene mutations: MR imaging findings. 53 62 5
12812953 2003
20
Genotyping microsatellite DNA markers at putative disease loci in inbred/multiplex families with respiratory chain complex I deficiency allows rapid identification of a novel nonsense mutation (IVS1nt -1) in the NDUFS4 gene in Leigh syndrome. 53 62 5
12616398 2003
21
Leigh syndrome with cytochrome-c oxidase deficiency and a single T insertion nt 5537 in the mitochondrial tRNATrp gene. 53 62 5
12776230 2003
22
A novel mutation in the SURF1 gene in a child with Leigh disease, peripheral neuropathy, and cytochrome-c oxidase deficiency. 53 62 5
12026244 2002
23
Missense mutations in SURF1 associated with deficient cytochrome c oxidase assembly in Leigh syndrome patients. 53 62 5
10746561 2000
24
Characterization of SURF-1 expression and Surf-1p function in normal and disease conditions. 53 62 5
10556302 1999
25
SURFEIT-1 gene analysis and two-dimensional blue native gel electrophoresis in cytochrome c oxidase deficiency. 53 62 5
10558868 1999
26
Loss-of-function mutations of SURF-1 are specifically associated with Leigh syndrome with cytochrome c oxidase deficiency. 53 62 5
10443880 1999
27
Mutations of SURF-1 in Leigh disease associated with cytochrome c oxidase deficiency. 53 62 5
9837813 1998
28
Clinical Diagnosis and Treatment of Leigh Syndrome Based on SURF1: Genotype and Phenotype. 62 5
34943053 2021
29
Pediatric Leigh Syndrome: Neuroimaging Features and Genetic Correlations. 62 5
32445240 2020
30
Mortality of Japanese patients with Leigh syndrome: Effects of age at onset and genetic diagnosis. 62 5
31967322 2020
31
Phenotypic variability and mutation hotspot in COX15-related Leigh syndrome. 62 5
32232962 2020
32
Novel mutations in the mitochondrial complex I assembly gene NDUFAF5 reveal heterogeneous phenotypes. 62 5
30473481 2019
33
Genetic diversity of NDUFV1-dependent mitochondrial complex I deficiency. 62 5
29976978 2018
34
SURF1 mutations in Chinese patients with Leigh syndrome: Novel mutations, mutation spectrum, and the functional consequences. 62 5
29933018 2018
35
Clinical validity of biochemical and molecular analysis in diagnosing Leigh syndrome: a study of 106 Japanese patients. 62 5
28429146 2017
36
The clinical and genetic characteristics in children with mitochondrial disease in China. 62 5
28639102 2017
37
Whole Exome Sequencing Identifies the Genetic Basis of Late-Onset Leigh Syndrome in a Patient with MRI but Little Biochemical Evidence of a Mitochondrial Disorder. 62 5
27344648 2017
38
Identification of a novel deletion in SURF1 gene: Heterogeneity in Leigh syndrome with COX deficiency. 62 5
27756633 2016
39
Leigh syndrome associated with a novel mutation in the COX15 gene. 62 5
26959537 2016
40
Ndufs4 related Leigh syndrome: A case report and review of the literature. 62 5
27079373 2016
41
Leigh syndrome: One disorder, more than 75 monogenic causes. 62 57
26506407 2016
42
Metabolic rescue in pluripotent cells from patients with mtDNA disease. 62 57
26176921 2015
43
Mutation in the nuclear-encoded mitochondrial isoleucyl-tRNA synthetase IARS2 in patients with cataracts, growth hormone deficiency with short stature, partial sensorineural deafness, and peripheral neuropathy or with Leigh syndrome. 62 5
25130867 2014
44
Clinical and magnetic resonance imaging findings in patients with Leigh syndrome and SURF1 mutations. 62 5
24262866 2014
45
A founder mutation in PET100 causes isolated complex IV deficiency in Lebanese individuals with Leigh syndrome. 62 5
24462369 2014
46
Rapid identification of a novel complex I MT-ND3 m.10134C>A mutation in a Leigh syndrome patient. 62 5
25118196 2014
47
Non-invasive screening of cytochrome c oxidase deficiency in children using a dipstick immunocapture assay. 62 5
25629267 2014
48
Diagnosis of mitochondrial disorders by concomitant next-generation sequencing of the exome and mitochondrial genome. 62 5
23631824 2013
49
SURF1 deficiency: a multi-centre natural history study. 62 5
23829769 2013
50
Different laboratory and muscle biopsy findings in a family with an m.8851T>C mutation in the mitochondrial MTATP6 gene. 62 5
23206802 2013

Variations for Leigh Syndrome

ClinVar genetic disease variations for Leigh Syndrome:

5 (show top 50) (show all 2890)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SURF1 NM_003172.4(SURF1):c.586C>T (p.Gln196Ter) SNV Pathogenic
243077 rs147816470 GRCh37: 9:136219551-136219551
GRCh38: 9:133352696-133352696
2 IARS2 NM_018060.4(IARS2):c.1821G>A (p.Trp607Ter) SNV Pathogenic
156551 rs373436822 GRCh37: 1:220300169-220300169
GRCh38: 1:220126827-220126827
3 NDUFAF6 NM_152416.4(NDUFAF6):c.611C>T (p.Ala204Val) SNV Pathogenic
430872 rs1131692157 GRCh37: 8:96059252-96059252
GRCh38: 8:95047024-95047024
4 NDUFS4 NM_002495.4(NDUFS4):c.470_471del (p.Lys156_Ser157insTer) DEL Pathogenic
488560 rs1554062427 GRCh37: 5:52978993-52978994
GRCh38: 5:53683163-53683164
5 NDUFS4 NM_002495.4(NDUFS4):c.178-2A>G SNV Pathogenic
488559 rs1554059248 GRCh37: 5:52942061-52942061
GRCh38: 5:53646231-53646231
6 MRPS34 NM_023936.1(MRPS34):c.321+1G>T SNV Pathogenic
430586 rs1161932777 GRCh37: 16:1822799-1822799
GRCh38: 16:1772798-1772798
7 NDUFS4 NM_002495.4(NDUFS4):c.462del (p.Lys154fs) DEL Pathogenic
40257 rs587776949 GRCh37: 5:52978982-52978982
GRCh38: 5:53683152-53683152
8 NDUFS4 NM_002495.4(NDUFS4):c.99-1G>A SNV Pathogenic
496165 rs376281345 GRCh37: 5:52899281-52899281
GRCh38: 5:53603451-53603451
9 SURF1 NM_003172.4(SURF1):c.751C>T (p.Gln251Ter) SNV Pathogenic
12762 rs121918657 GRCh37: 9:136219301-136219301
GRCh38: 9:133352446-133352446
10 SURF1 NM_003172.4(SURF1):c.465_466del (p.Thr156fs) DEL Pathogenic
520391 rs1564349176 GRCh37: 9:136220653-136220654
GRCh38: 9:133353798-133353799
11 SURF1 NM_003172.4(SURF1):c.772C>T (p.Pro258Ser) SNV Pathogenic
520388 rs1053850536 GRCh37: 9:136218977-136218977
GRCh38: 9:133352122-133352122
12 FASTKD2 NM_001136193.2(FASTKD2):c.1861del (p.Ser621fs) DEL Pathogenic
800306 rs1574675683 GRCh37: 2:207653588-207653588
GRCh38: 2:206788864-206788864
13 FASTKD2 NM_001136193.2(FASTKD2):c.810_820dup (p.Ser274fs) DUP Pathogenic
800307 rs1574663066 GRCh37: 2:207634845-207634846
GRCh38: 2:206770121-206770122
14 FASTKD2 NM_001136193.2(FASTKD2):c.868C>T (p.Arg290Ter) SNV Pathogenic
800308 rs778120270 GRCh37: 2:207634905-207634905
GRCh38: 2:206770181-206770181
15 NDUFV1 NM_007103.4(NDUFV1):c.1207dup (p.Asp403fs) DUP Pathogenic
802694 rs766830864 GRCh37: 11:67379629-67379630
GRCh38: 11:67612158-67612159
16 SURF1 NM_003172.4(SURF1):c.236G>A (p.Trp79Ter) SNV Pathogenic
802529 rs1244071473 GRCh37: 9:136221683-136221683
GRCh38: 9:133354828-133354828
17 SURF1 NM_003172.4(SURF1):c.11_27dup (p.Gly10fs) DUP Pathogenic
802530 rs1588693841 GRCh37: 9:136223302-136223303
GRCh38: 9:133356426-133356427
18 SURF1 NM_003172.4(SURF1):c.834G>A (p.Trp278Ter) SNV Pathogenic
928763 rs782601312 GRCh37: 9:136218837-136218837
GRCh38: 9:133351982-133351982
19 FOXRED1 NM_017547.4(FOXRED1):c.694C>T (p.Gln232Ter) SNV Pathogenic
5 rs267606829 GRCh37: 11:126145284-126145284
GRCh38: 11:126275389-126275389
20 NDUFS4 NM_002495.4(NDUFS4):c.466_470dup (p.Lys158fs) DUP Pathogenic
6887 rs1445075330 GRCh37: 5:52978987-52978988
GRCh38: 5:53683157-53683158
21 NDUFA13 NM_015965.7(NDUFA13):c.194del (p.Phe65fs) DEL Pathogenic
983476 rs2061105702 GRCh37: 19:19638109-19638109
GRCh38: 19:19527300-19527300
22 NDUFA13 NM_015965.7(NDUFA13):c.107T>C (p.Leu36Pro) SNV Pathogenic
983478 rs2061098856 GRCh37: 19:19637003-19637003
GRCh38: 19:19526194-19526194
23 SURF1 NM_003172.4(SURF1):c.532_535del (p.Asn178fs) DEL Pathogenic
372719 rs1057517942 GRCh37: 9:136219602-136219605
GRCh38: 9:133352747-133352750
24 FOXRED1 NM_017547.4(FOXRED1):c.608_609del (p.Glu203fs) MICROSAT Pathogenic
972926 rs1189650128 GRCh37: 11:126144891-126144892
GRCh38: 11:126274996-126274997
25 SURF1 NM_003172.4(SURF1):c.240+1G>T SNV Pathogenic
379506 rs781948238 GRCh37: 9:136221678-136221678
GRCh38: 9:133354823-133354823
26 SURF1 NM_003172.4(SURF1):c.808_812del (p.Glu270fs) DEL Pathogenic
872973 rs1836430953 GRCh37: 9:136218937-136218941
GRCh38: 9:133352082-133352086
27 NDUFV1 NM_007103.4(NDUFV1):c.175C>T (p.Arg59Ter) SNV Pathogenic
14057 rs768050261 GRCh37: 11:67376042-67376042
GRCh38: 11:67608571-67608571
28 SURF1 NM_003172.4(SURF1):c.367_368del (p.Arg123fs) DEL Pathogenic
1182215 GRCh37: 9:136220751-136220752
GRCh38: 9:133353896-133353897
29 SURF1 NM_003172.4(SURF1):c.595_598del (p.Gly199fs) DEL Pathogenic
1320126 GRCh37: 9:136219454-136219457
GRCh38: 9:133352599-133352602
30 SURF1 NM_003172.4(SURF1):c.283del (p.Glu95fs) DEL Pathogenic
1320241 GRCh37: 9:136221554-136221554
GRCh38: 9:133354699-133354699
31 NDUFAF6 NM_152416.4(NDUFAF6):c.337C>T (p.Arg113Ter) SNV Pathogenic
972921 rs753873681 GRCh37: 8:96047721-96047721
GRCh38: 8:95035493-95035493
32 SURF1 NM_003172.4(SURF1):c.867G>A (p.Trp289Ter) SNV Pathogenic
1321366 GRCh37: 9:136218804-136218804
GRCh38: 9:133351949-133351949
33 SURF1 NM_003172.4(SURF1):c.273del (p.Ile91fs) DEL Pathogenic
1388760 GRCh37: 9:136221564-136221564
GRCh38: 9:133354709-133354709
34 SURF1 NM_003172.4(SURF1):c.58_59dup (p.Ala21fs) DUP Pathogenic
1397724 GRCh37: 9:136223170-136223171
GRCh38: 9:133356315-133356316
35 SURF1 NM_003172.4(SURF1):c.577C>T (p.Gln193Ter) SNV Pathogenic
1363063 GRCh37: 9:136219560-136219560
GRCh38: 9:133352705-133352705
36 SURF1 NM_003172.4(SURF1):c.632_642del (p.Glu211fs) DEL Pathogenic
1413577 GRCh37: 9:136219410-136219420
GRCh38: 9:133352555-133352565
37 SURF1 NM_003172.4(SURF1):c.552del (p.Lys185fs) DEL Pathogenic
1416074 GRCh37: 9:136219585-136219585
GRCh38: 9:133352730-133352730
38 SURF1 NM_003172.4(SURF1):c.773_784del (p.Pro258_Gly261del) DEL Pathogenic
1459173 GRCh37: 9:136218965-136218976
GRCh38: 9:133352110-133352121
39 SURF1 NM_003172.4(SURF1):c.485_486del (p.Val162fs) MICROSAT Pathogenic
1451209 GRCh37: 9:136220633-136220634
GRCh38: 9:133353778-133353779
40 NDUFAF5 NM_024120.5(NDUFAF5):c.836T>G (p.Met279Arg) SNV Pathogenic
225036 rs761389904 GRCh37: 20:13797166-13797166
GRCh38: 20:13816520-13816520
41 SURF1 NM_003172.4(SURF1):c.32_38dup (p.Leu16fs) DUP Pathogenic
456665 rs1410388157 GRCh37: 9:136223291-136223292
GRCh38: 9:133356415-133356416
42 MT-ND5 m.13045A>C SNV Pathogenic
9700 rs267606895 GRCh37: MT:13045-13045
GRCh38: MT:13045-13045
43 MT-ND5 m.13084A>T SNV Pathogenic
9701 rs267606896 GRCh37: MT:13084-13084
GRCh38: MT:13084-13084
44 MT-ND3 NC_012920.1:m.10134C>A SNV Pathogenic
156375 rs587780529 GRCh37: MT:10134-10134
GRCh38: MT:10134-10134
45 SURF1 NM_003172.4(SURF1):c.-11_13del (p.Met1_Ala5del) DEL Pathogenic
215241 rs863224229 GRCh37: 9:136223317-136223340
GRCh38: 9:133356441-133356464
46 SURF1 NM_003172.4(SURF1):c.688C>T (p.Arg230Ter) SNV Pathogenic
280010 rs782623477 GRCh37: 9:136219364-136219364
GRCh38: 9:133352509-133352509
47 MT-ND2 NC_012920.1(MT-ND2):m.5001dup DUP Pathogenic
692533 rs1603219713 GRCh37: MT:4997-4998
GRCh38: MT:4997-4998
48 MT-CYB m.15242G>A SNV Pathogenic
9680 rs207459999 GRCh37: MT:15242-15242
GRCh38: MT:15242-15242
49 SURF1 NM_003172.4(SURF1):c.312_321delinsAT (p.Pro104_Leu105insTer) INDEL Pathogenic
Pathogenic
215237 rs863224228 GRCh37: 9:136221516-136221525
GRCh38: 9:133354661-133354670
50 MT-ND1 m.3946G>A SNV Pathogenic
9734 rs199476123 GRCh37: MT:3946-3946
GRCh38: MT:3946-3946

UniProtKB/Swiss-Prot genetic disease variations for Leigh Syndrome:

73 (show all 13)
# Symbol AA change Variation ID SNP ID
1 MT-ATP6 p.Leu156Arg VAR_000793 rs199476133
2 MT-ATP6 p.Leu156Pro VAR_000794 rs199476133
3 MT-ATP6 p.Leu217Pro VAR_000797 rs199476135
4 MT-ATP6 p.Leu220Pro VAR_073700 rs199476138
5 MT-ND3 p.Ala47Thr VAR_035092 rs267606891
6 MT-ND5 p.Phe124Leu VAR_035424 rs267606893
7 MT-ND5 p.Ser250Cys VAR_035429 rs267606896
8 MT-ND6 p.Met63Val VAR_064568 rs199476109
9 POLG p.Gly848Ser VAR_023675 rs113994098
10 POLG p.Arg232His VAR_058871 rs113994093
11 SDHA p.Arg554Trp VAR_002449 rs9809219
12 SDHA p.Ala524Val VAR_016878 rs137852767
13 SDHA p.Cys189Gly VAR_074022

Expression for Leigh Syndrome

Search GEO for disease gene expression data for Leigh Syndrome.

Pathways for Leigh Syndrome

GO Terms for Leigh Syndrome

Cellular components related to Leigh Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 10.17 SURF1 SDHA NDUFV1 NDUFS4 NDUFAF6 NDUFAF5
2 mitochondrial respiratory chain complex I GO:0005747 10.16 FOXRED1 MT-ND1 MT-ND2 MT-ND3 MT-ND5 MT-ND6
3 mitochondrial inner membrane GO:0005743 9.84 BCS1L COX15 FOXRED1 MRPS34 MT-ATP6 MT-ND1
4 respirasome GO:0070469 9.76 NDUFV1 NDUFS4 MT-ND6 MT-ND5 MT-ND3 MT-ND2
5 mitochondrial membrane GO:0031966 9.72 MT-ND6 MT-ND3 MT-ND1 COX15
6 mitochondrial respirasome GO:0005746 9.67 SURF1 COX15

Biological processes related to Leigh Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial electron transport, NADH to ubiquinone GO:0006120 10.1 NDUFV1 NDUFS4 MT-ND6 MT-ND5 MT-ND3 MT-ND2
2 aerobic respiration GO:0009060 10.06 MT-ND1 MT-ND2 MT-ND3 MT-ND5 MT-ND6 NDUFS4
3 proton motive force-driven mitochondrial ATP synthesis GO:0042776 9.91 MT-ATP6 MT-ND1 MT-ND2 MT-ND3 MT-ND5 MT-ND6
4 electron transport chain GO:0022900 9.87 SURF1 SDHA NDUFV1 NDUFS4 MT-ND3 MT-ND1
5 respiratory chain complex IV assembly GO:0008535 9.67 SURF1 COX15
6 mitochondrial respiratory chain complex I assembly GO:0032981 9.62 NDUFS4 NDUFAF6 NDUFAF5 NDUFAF2 MT-ND6 MT-ND5

Molecular functions related to Leigh Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.7 SDHA NDUFV1 NDUFAF5 MT-ND2 FOXRED1
2 cytochrome-c oxidase activity GO:0004129 9.62 SURF1 COX15
3 NADH dehydrogenase (ubiquinone) activity GO:0008137 9.47 NDUFV1 NDUFS4 MT-ND6 MT-ND5 MT-ND3 MT-ND2
4 oxidoreductase activity, acting on the CH-CH group of donors GO:0016627 9.43 SDHA COX15
5 NADH dehydrogenase activity GO:0003954 9.26 MT-ND5 MT-ND1

Sources for Leigh Syndrome

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 24-Oct-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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