Isolated NADH-CoQ reductase deficiency

General Information (adopted from Orphanet):

Synonyms, Signs: MITOCHONDRIAL NADH DEHYDROGENASE COMPONENT OF COMPLEX I, DEFICIENCY OF
NADH-COENZYME Q REDUCTASE DEFICIENCY
NADH:Q(1) OXIDOREDUCTASE DEFICIENCY
Isolated NADH-coenzyme Q reductase deficiency
Isolated mitochondrial respiratory chain complex I deficiency
Isolated NADH-ubiquinone reductase deficiency
Number of Symptoms 51
OrphanetNr: 2609
OMIM Id: 252010
ICD-10: G71.3
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Mitochondrial
X-linked
Autosomal recessive
X-linked dominant
[Omim]
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: Isolated oxidative phosphorylation complex disorder
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare neurologic disease
Mitochondrial myopathy
 -Rare genetic disease
 -Rare neurologic disease
Neurometabolic disease
 -Rare genetic disease
 -Rare neurologic disease
X-linked syndromic intellectual deficit
 -Rare genetic disease
 -Rare neurologic disease

Symptom Information: Sort by abundance 

1
(HPO:0001992) Organic aciduria Very frequent [Orphanet] 28 / 7739
2
(HPO:0004481) Progressive macrocephaly 8 / 7739
3
(HPO:0000508) Ptosis 459 / 7739
4
(HPO:0000639) Nystagmus 555 / 7739
5
(HPO:0000543) Optic disc pallor 67 / 7739
6
(HPO:0000618) Blindness 124 / 7739
7
(HPO:0000486) Strabismus 576 / 7739
8
(HPO:0000407) Sensorineural hearing impairment 524 / 7739
9
(HPO:0001257) Spasticity 251 / 7739
10
(HPO:0001265) Hyporeflexia 208 / 7739
11
(HPO:0001347) Hyperreflexia 363 / 7739
12
(HPO:0001263) Global developmental delay 853 / 7739
13
(HPO:0001250) Seizures 1245 / 7739
14
(HPO:0001298) Encephalopathy 72 / 7739
15
(HPO:0006965) Acute necrotizing encephalopathy 2 / 7739
16
(HPO:0001259) Coma 65 / 7739
17
(HPO:0002376) Developmental regression 74 / 7739
18
(HPO:0001254) Lethargy 104 / 7739
19
(HPO:0002490) Increased CSF lactate 28 / 7739
20
(HPO:0003487) Babinski sign 179 / 7739
21
(HPO:0001251) Ataxia 413 / 7739
22
(HPO:0001399) Hepatic failure 80 / 7739
23
(HPO:0011968) Feeding difficulties 240 / 7739
24
(HPO:0002013) Vomiting 191 / 7739
25
(HPO:0008872) Feeding difficulties in infancy 153 / 7739
26
(HPO:0001510) Growth delay 295 / 7739
27
(HPO:0001508) Failure to thrive 454 / 7739
28
(HPO:0001639) Hypertrophic cardiomyopathy 137 / 7739
29
(HPO:0001943) Hypoglycemia 131 / 7739
30
(HPO:0008316) Abnormal mitochondria in muscle tissue 5 / 7739
31
(HPO:0002181) Cerebral edema 19 / 7739
32
(HPO:0003128) Lactic acidosis 116 / 7739
33
(HPO:0002093) Respiratory insufficiency 410 / 7739
34
(HPO:0002878) Respiratory failure 57 / 7739
35
(HPO:0003546) Exercise intolerance 62 / 7739
36
(HPO:0003202) Skeletal muscle atrophy 281 / 7739
37
(HPO:0008947) Infantile muscular hypotonia 482 / 7739
38
(HPO:0001324) Muscle weakness 859 / 7739
39
(HPO:0001252) Muscular hypotonia 990 / 7739
40
(HPO:0010547) Muscle flaccidity 466 / 7739
41
(OMIM) Striatal lesions 1 / 7739
42
(OMIM) Thalamic lesions 2 / 7739
43
(OMIM) Cavitating leukoencephalopathy 7 / 7739
44
(OMIM) Muscle biopsy shows abnormal mitochondria 1 / 7739
45
(OMIM) Leigh syndrome 7 / 7739
46
(HPO:0001272) Cerebellar atrophy 197 / 7739
47
(OMIM) Cerebellar lesions 1 / 7739
48
(OMIM) Brainstem lesions, hyperintense on T2-weighted imaging 2 / 7739
49
(OMIM) Decreased activity of mitochondrial respiratory chain complex I 1 / 7739
50
(MedDRA:10054859) Myoclonic epilepsy 7 / 7739
51
(HPO:0002415) Leukodystrophy 30 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Isolated complex I deficiency is the most common enzymatic defect of the oxidative phosphorylation disorders (McFarland et al., 2004; Kirby et al., 2004). It causes a wide range of clinical disorders, ranging from lethal neonatal disease to adult-onset ...
Clinical Description OMIM - Patients with Unknown Mutations

Morgan-Hughes et al. (1979) presented the first report of isolated complex I deficiency. Two sisters had a mitochondrial myopathy characterized by weakness, marked exercise intolerance, and fluctuating lactic acidemia. Increased weakness ...

Genotype-Phenotype Correlations OMIM Mutations in the nuclear-encoded genes NDUFS1, NDUFS4, NDUFS7, NDUFS8, and NDUFV1 result in neurologic diseases, mostly Leigh syndrome or Leigh-like syndrome. Mutations in NDUFS2 and NDUFV2 have been associated with hypertrophic cardiomyopathy and encephalomyopathy. Mutations in the mitochondrial-encoded ...
Molecular genetics OMIM Smeitink and van den Heuvel (1999) reviewed the nuclear gene mutations that had been identified in patients with isolated complex I deficiency. These included a 5-bp duplication in the NDUFS4 gene (602694.0001), a double mutation in the NDUFS8 ...