ORPHA:2609

Isolated complex I deficiency

Synonyms: Isolated NADH-CoQ reductase deficiency · Isolated NADH-coenzyme Q reductase deficiency · Isolated NADH-ubiquinone reductase deficiency · Isolated mitochondrial respiratory chain complex I deficiency

Type: Disease
Group: Disorder
Inheritance: Autosomal recessive, Mitochondrial inheritance, X-linked dominant
Age of onset: All ages
Status: active

Isolated complex I deficiency is a rare inborn error of metabolism due to mutations in nuclear or mitochondrial genes encoding subunits or assembly factors of the human mitochondrial complex I (NADH: ubiquinone oxidoreductase) and is characterized by a wide range of manifestations including marked and often fatal lactic acidosis, cardiomyopathy, leukoencephalopathy, pure myopathy and hepatopathy with tubulopathy. Among the numerous clinical phenotypes observed are Leigh syndrome, Leber hereditary optic neuropathy and MELAS syndrome.

Names in Orphadata languages

12 of 12 languages

Lang	Name	Synonyms
en	Isolated complex I deficiency	Isolated NADH-CoQ reductase deficiency · Isolated NADH-coenzyme Q reductase deficiency · Isolated NADH-ubiquinone reductase deficiency · Isolated mitochondrial respiratory chain complex I deficiency
fr	Déficit isolé en complexe I	Déficit isolé en NADH-CoQ réductase · Déficit isolé en NADH-coenzyme Q réductase · Déficit isolé en NADH-ubiquinone réductase · Déficit isolé en complexe I de la chaîne respiratoire mitochondriale
de	Isolierter Atmungskettendefekt im Komplex I	NADH-CoQ-Reduktase Mangel, isolierter · NADH-Coenzym-Q-Reduktase-Mangel, isolierter · NADH-Ubiquinon-Reduktase-Mangel, isolierter
es	Deficiencia aislada del complejo I	Deficiencia aislada de NADH-CoQ reductasa · Deficiencia aislada de NADH-coenzima Q reductasa · Deficiencia aislada de NADH-ubiquinona reductasa · Deficiencia aislada del complejo I de la cadena respiratoria mitocondrial
it	Deficit isolato del complesso I	Deficit isolato del complesso I della catena respiratoria mitocondriale · Deficit isolato di NADH-CoQ reduttasi · Deficit isolato di NADH-Coenzima Q reduttasi · Deficit isolato di NADH-ubichinone reduttasi
nl	Geïsoleerde complex I-deficiëntie	Geïsoleerde NADH-CoQ-reductasedeficiëntie · Geïsoleerde NADH-co-enzym Q-reductasedeficiëntie · Geïsoleerde NADH-ubiquinonreductasedeficiëntie · Geïsoleerde mitochondriale ademhalingsketencomplex I-deficiëntie
pt	Deficiência de complexo I isolada	Deficiência de NADH-CoQ redutase · Deficiência de complexo 1 da cadeia respiratória mitocondrial
pl	Izolowany Niedobór reduktazy NADH-CoQ	Izolowany Niedobór kompleksu I mitochondrialnego łańcucha oddechowego · Izolowany Niedobór reduktazy NADH-koenzym Q · Izolowany Niedobór reduktazy NADH-ubikwinon
cs	Izolovaný deficit komplexu I	Izolovaný deficit NADH-CoQ reduktázy · Izolovaný deficit NADH-koenzym Q reduktázy · Izolovaný deficit NADH-ubichinon reduktázy · Izolovaný deficit mitochondriálního respiračního řetězce komplexu I
uk	Ізольований дефіцит комплексу I	Ізольований дефіцит комплексу I мітохондріального дихального ланцюга · Ізольований дефіцит NADH-коензиму Q-редуктази · Ізольований дефіцит NADH-CoQ-редуктази · Ізольований дефіцит НАДН-убіхінон-редуктази
zh	孤立型复合物I缺乏	孤立型线粒体呼吸链复合物I缺乏症
tr	İzole kompleks I eksikliği	İzole NADH-CoQ redüktaz eksikliği · İzole NADH-koenzim Q redüktaz eksikliği · İzole NADH-ubikinon redüktaz eksikliği · İzole mitokondriyal solunum zinciri kompleksi I eksikliği

Definition in:

Cross-references

qualifier = Orphanet mapping relation

Source	Code	Qualifier	ICD relation	Validation
OMIM	252010	E		validated
OMIM	301020	BTNT		validated
OMIM	301021	BTNT		validated
OMIM	618222	BTNT		validated
OMIM	618224	BTNT		validated
OMIM	618225	BTNT		validated
OMIM	618226	BTNT		validated
OMIM	618228	BTNT		validated
OMIM	618229	BTNT		validated
OMIM	618230	BTNT		validated
OMIM	618232	BTNT		validated
OMIM	618233	BTNT		validated
OMIM	618234	BTNT		validated
OMIM	618236	BTNT		validated
OMIM	618237	BTNT		validated
OMIM	618238	BTNT		validated
OMIM	618240	BTNT		validated
OMIM	618241	BTNT		validated
OMIM	618242	BTNT		validated
OMIM	618244	BTNT		validated
OMIM	618245	BTNT		validated
OMIM	618246	BTNT		validated
OMIM	618247	BTNT		validated
OMIM	618250	BTNT		validated
OMIM	618251	BTNT		validated
OMIM	618253	BTNT		validated
OMIM	618776	BTNT		validated
OMIM	619003	BTNT		validated
OMIM	619170	BTNT		validated
OMIM	619272	BTNT		validated
OMIM	620135	BTNT		validated
ICD-10	G71.3	NTBT	attributed	validated
ICD-11	5C53.2Y	NTBT	index	validated
MONDO	0100133	E		validated
MeSH	C537475	E		validated
UMLS	C1838979	E		validated
GARD	3908	E		validated

E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.

Classification

Preferential parent (Orphanet linearisation):

ORPHA:68367Rare inborn error of metabolism

Parents in the classifications (5):

ORPHA:254846Isolated oxidative phosphorylation complex disorder
rare inborn errors of metabolism; rare genetic diseases
ORPHA:225700Mitochondrial disease with epilepsy
rare genetic diseases; rare neurological diseases
ORPHA:206966Mitochondrial myopathy
rare genetic diseases; rare neurological diseases
ORPHA:68385Neurometabolic disease
rare genetic diseases; rare neurological diseases
ORPHA:611314Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome
rare genetic diseases; rare neurological diseases

No children.

Codes that Orphanet moved or referred to this one:

ORPHA:936Succinic acidemia moved to · inactive
ORPHA:289527OBSOLETE: Fatal infantile hypertrophic cardiomyopathy due to mitochondrial complex I deficiency referred to · inactive

Genes

30 direct

Gene	Association	Status	HGNC	Ensembl	OMIM	Locus	Name	Source of validation
NDUFB11	Candidate gene tested in	Not yet assessed	HGNC:20372	ENSG00000147123	300403	Xp11.3	NADH:ubiquinone oxidoreductase subunit B11	26741492[PMID]
TIMMDC1	Disease-causing germline mutation(s) (loss of function) in	Assessed	HGNC:1321	ENSG00000113845	615534	3q13.33	translocase of inner mitochondrial membrane domain containing 1	28604674[PMID]
TMEM126B	Disease-causing germline mutation(s) (loss of function) in	Assessed	HGNC:30883	ENSG00000171204	615533	11q14.1	transmembrane protein 126B	27374773[PMID]_27374774[PMID]
FOXRED1	Disease-causing germline mutation(s) in	Assessed	HGNC:26927	ENSG00000110074	613622	11q24.2	FAD dependent oxidoreductase domain containing 1	20858599[PMID]
MT-ND1	Disease-causing germline mutation(s) in	Assessed	HGNC:7455	ENSG00000198888	516000	mitochondria	mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1	10775530[PMID]_16492986[PMID]
MT-ND2	Disease-causing germline mutation(s) in	Assessed	HGNC:7456	ENSG00000198763	516001	mitochondria	mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 2	12192017[PMID]_15781840[PMID]
MT-ND3	Disease-causing germline mutation(s) in	Assessed	HGNC:7458	ENSG00000198840	516002	mitochondria	mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 3	14705112[PMID]
NDUFA1	Disease-causing germline mutation(s) in	Assessed	HGNC:7683	ENSG00000125356	300078	Xq24	NADH:ubiquinone oxidoreductase subunit A1	17262856[PMID]_19185523[PMID]_21596602[PMID]_22644603[PMID]
NDUFA11	Disease-causing germline mutation(s) in	Assessed	HGNC:20371	ENSG00000174886	612638	19p13.3	NADH:ubiquinone oxidoreductase subunit A11	18306244[PMID]_22644603[PMID]
NDUFA6	Disease-causing germline mutation(s) in	Assessed	HGNC:7690	ENSG00000184983	602138	22q13.2	NADH:ubiquinone oxidoreductase subunit A6	30245030[PMID]
NDUFA9	Disease-causing germline mutation(s) in	Assessed	HGNC:7693			1p36.13	NADH:ubiquinone oxidoreductase subunit A9	41069424[PMID]
NDUFAF1	Disease-causing germline mutation(s) in	Assessed	HGNC:18828	ENSG00000137806	606934	15q15.1	NADH:ubiquinone oxidoreductase complex assembly factor 1	17557076[PMID]
NDUFAF2	Disease-causing germline mutation(s) in	Assessed	HGNC:28086	ENSG00000164182	609653	5q12.1	NADH:ubiquinone oxidoreductase complex assembly factor 2	16200211[PMID]
NDUFAF3	Disease-causing germline mutation(s) in	Assessed	HGNC:29918	ENSG00000178057	612911	3p21.31	NADH:ubiquinone oxidoreductase complex assembly factor 3	19463981[PMID]_22644603[PMID]
NDUFAF4	Disease-causing germline mutation(s) in	Assessed	HGNC:21034	ENSG00000123545	611776	6q16.1	NADH:ubiquinone oxidoreductase complex assembly factor 4	18179882[PMID]_22644603[PMID]
NDUFAF5	Disease-causing germline mutation(s) in	Assessed	HGNC:15899	ENSG00000101247	612360	20p12.1	NADH:ubiquinone oxidoreductase complex assembly factor 5	18940309[PMID]_22644603[PMID]
NDUFAF8	Disease-causing germline mutation(s) in	Assessed	HGNC:33551	ENSG00000224877	618461	17q25.3	NADH:ubiquinone oxidoreductase complex assembly factor 8	31866046[PMID]
NDUFB10	Disease-causing germline mutation(s) in	Assessed	HGNC:7696	ENSG00000140990	603843	16p13.3	NADH:ubiquinone oxidoreductase subunit B10	28040730[PMID]
NDUFB3	Disease-causing germline mutation(s) in	Assessed	HGNC:7698	ENSG00000119013	603839	2q33.1	NADH:ubiquinone oxidoreductase subunit B3	22277967[PMID]_22499348[PMID]
NDUFB9	Disease-causing germline mutation(s) in	Assessed	HGNC:7704	ENSG00000147684	601445	8q24.13	NADH:ubiquinone oxidoreductase subunit B9	22200994[PMID]
NDUFS1	Disease-causing germline mutation(s) in	Assessed	HGNC:7707	ENSG00000023228	157655	2q33.3	NADH:ubiquinone oxidoreductase core subunit S1	20382551[PMID]_22644603[PMID]
NDUFS2	Disease-causing germline mutation(s) in	Assessed	HGNC:7708	ENSG00000158864	602985	1q23.3	NADH:ubiquinone oxidoreductase core subunit S2	15576045[PMID]_22644603[PMID]
NDUFS3	Disease-causing germline mutation(s) in	Assessed	HGNC:7710	ENSG00000213619	603846	11p11.2	NADH:ubiquinone oxidoreductase core subunit S3	22499348[PMID]
NDUFS4	Disease-causing germline mutation(s) in	Assessed	HGNC:7711	ENSG00000164258	602694	5q11.2	NADH:ubiquinone oxidoreductase subunit S4	9463323[PMID]_22644603[PMID]
NDUFS6	Disease-causing germline mutation(s) in	Assessed	HGNC:7713	ENSG00000145494	603848	5p15.33	NADH:ubiquinone oxidoreductase subunit S6	15372108[PMID]_19259137[PMID]_22644603[PMID]
NDUFS7	Disease-causing germline mutation(s) in	Assessed	HGNC:7714	ENSG00000115286	601825	19p13.3	NADH:ubiquinone oxidoreductase core subunit S7	22644603[PMID]
NDUFS8	Disease-causing germline mutation(s) in	Assessed	HGNC:7715	ENSG00000110717	602141	11q13.2	NADH:ubiquinone oxidoreductase core subunit S8	22499348[PMID]_22644603[PMID]
NDUFV1	Disease-causing germline mutation(s) in	Assessed	HGNC:7716	ENSG00000167792	161015	11q13.2	NADH:ubiquinone oxidoreductase core subunit V1	22644603[PMID]
NDUFV2	Disease-causing germline mutation(s) in	Assessed	HGNC:7717	ENSG00000178127	600532	18p11.22	NADH:ubiquinone oxidoreductase core subunit V2	12754703[PMID]_22644603[PMID]_26008862[PMID]
NUBPL	Disease-causing germline mutation(s) in	Assessed	HGNC:20278	ENSG00000151413	613621	14q12	NUBP iron-sulfur cluster assembly factor, mitochondrial	20818383[PMID]_22644603[PMID]_23553477[PMID]

Prevalence and incidence

1 record

Type	Class	Value	Area	Qualification	Validation	Source
Point prevalence	Unknown	—	Worldwide	Class only	Validated	ORPHANET_15190193[PMID]_20818732[PMID]

Value is Orphadata's ValMoy: the mean estimate per 100 000 for prevalence and incidence, the number of cases or families for case reports.

HPO phenotypes

37 annotations · validated 2017-07-01

HPO	Term (as annotated by Orphanet)	Diagnostic
Obligate (100%)
HP:0011923	Decreased activity of mitochondrial complex I
Very frequent (99-80%)
HP:0008316	Abnormal mitochondria in muscle tissue
HP:0001251	Ataxia
HP:0001298	Encephalopathy
HP:0001508	Failure to thrive
HP:0012748	Focal T2 hyperintense brainstem lesion
HP:0001263	Global developmental delay
HP:0002240	Hepatomegaly
HP:0001639	Hypertrophic cardiomyopathy
HP:0001943	Hypoglycemia
HP:0001252	Hypotonia
HP:0002490	Increased CSF lactate
HP:0003542	Increased circulating pyruvate concentration
HP:0001511	Intrauterine growth retardation
HP:0003128	Lactic acidosis
HP:0001254	Lethargy
HP:0002415	Leukodystrophy
HP:0002352	Leukoencephalopathy
HP:0003737	Mitochondrial myopathy
HP:0001324	Muscle weakness
HP:0000639	Nystagmus
HP:0000543	Optic disc pallor
HP:0001138	Optic neuropathy
HP:0007704	Paroxysmal involuntary eye movements
HP:0002421	Poor head control
HP:0000114	Proximal tubulopathy
HP:0000508	Ptosis
HP:0000817	Reduced eye contact
HP:0002093	Respiratory insufficiency
HP:0000407	Sensorineural hearing impairment
HP:0000486	Strabismus
HP:0002013	Vomiting
Occasional (29-5%)
HP:0000618	Blindness
HP:0000819	Diabetes mellitus
HP:0011968	Feeding difficulties
HP:0025116	Fetal distress
HP:0000252	Microcephaly

Run the differential on the 12 obligate / very frequent terms

Annotation source: 30095618[PMID]_9463323[PMID]

Sources for this card

Orphanet page: orpha.net/en/disease/detail/2609
This record as JSON: /data/d/2609.json