Renal tubulopathy - encephalopathy - liver failure

General Information (adopted from Orphanet):

Synonyms, Signs: MC3DN1
Number of Symptoms 46
OrphanetNr: 254902
OMIM Id: 124000
ICD-10:
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: Neonatal
Infancy
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Mitochondrial disorder due to a defect in assembly or maturation of the respiratory chain complexes
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare neurologic disease

Symptom Information: Sort by abundance 

1
 (HPO:0001970) Tubulointerstitial nephritis 27 / 7739
2
 (HPO:0003355) Aminoaciduria 65 / 7739
3
 (HPO:0010697) Anterior pyramidal cataract 22 / 7739
4
 (HPO:0000518) Cataract 454 / 7739
5
 (HPO:0000365) Hearing impairment 539 / 7739
6
 (HPO:0001250) Seizures 1245 / 7739
7
 (HPO:0001257) Spasticity 251 / 7739
8
 (HPO:0002353) EEG abnormality 188 / 7739
9
 (HPO:0001249) Intellectual disability 1089 / 7739
10
 (HPO:0001347) Hyperreflexia 363 / 7739
11
 (HPO:0006789) Mitochondrial encephalopathy 5 / 7739
12
 (HPO:0001263) Global developmental delay 853 / 7739
13
 (HPO:0002910) Elevated hepatic transaminases 158 / 7739
14
 (HPO:0001410) Decreased liver function 59 / 7739
15
 (HPO:0011968) Feeding difficulties 240 / 7739
16
 (HPO:0001396) Cholestasis 136 / 7739
17
 (HPO:0001414) Microvesicular hepatic steatosis 9 / 7739
18
 (HPO:0001508) Failure to thrive 454 / 7739
19
 (HPO:0002299) Brittle hair 52 / 7739
20
 (HPO:0001808) Fragile nails 21 / 7739
21
 (HPO:0004779) Brittle scalp hair 4 / 7739
22
 (HPO:0009886) Trichorrhexis nodosa 12 / 7739
23
 (HPO:0001942) Metabolic acidosis 81 / 7739
24
 (HPO:0002151) Increased serum lactate 92 / 7739
25
 (HPO:0001943) Hypoglycemia 131 / 7739
26
 (HPO:0003128) Lactic acidosis 116 / 7739
27
 (HPO:0010547) Muscle flaccidity 466 / 7739
28
 (HPO:0008947) Infantile muscular hypotonia 482 / 7739
29
 (HPO:0001252) Muscular hypotonia 990 / 7739
30
 (HPO:0001324) Muscle weakness 859 / 7739
31
 (MedDRA:10061296) Motor dysfunction 4 / 7739
32
 (OMIM) [DEL]Ragged red fibers seen on muscle biopsy 10 / 7739
33
 (OMIM) Biopsy shows fibrosis 1 / 7739
34
 (OMIM) White matter lesions may occur in the thalami, basal ganglia, and periventricular white matter (see Leigh syndrome, 256000) 1 / 7739
35
 (OMIM) Decreased mitochondrial complex III activity 3 / 7739
36
 (OMIM) Renal tubulopathy 4 / 7739
37
 (HPO:0001272) Cerebellar atrophy 197 / 7739
38
 (OMIM) Decreased respiratory chain complex III activity in multiple tissues 1 / 7739
39
 (OMIM) Hepatosiderosis 2 / 7739
40
 (OMIM) Other mitochondrial complex enzyme activities may also be decreased 1 / 7739
41
 (OMIM) Coagulation defect due to decreased liver function 1 / 7739
42
 (OMIM) Decreased complex III activity in liver tissue 1 / 7739
43
 (OMIM) Poor growth, postnatal 8 / 7739
44
 (HPO:0002059) Cerebral atrophy 171 / 7739
45
 (MedDRA:10008604) Cholangitis 6 / 7739
46
 (OMIM) Poor prenatal growth 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Autosomal recessive mitochondrial complex III deficiency is a severe multisystem disorder with onset at birth of lactic acidosis, hypotonia, hypoglycemia, failure to thrive, encephalopathy, and delayed psychomotor development. Visceral involvement, including hepatopathy and renal tubulopathy, may also occur. ...
Clinical Description OMIM De Lonlay et al. (2001) reported 6 patients from 4 unrelated Turkish families with complex III deficiency who presented with neonatal proximal tubulopathy, hepatic involvement, and encephalopathy. The first patient was a girl born to consanguineous parents after ...
Molecular genetics OMIM In 6 patients with complex III deficiency, de Lonlay et al. (2001) identified biallelic mutations in the BCS1L gene (603647.0001-603647.0004). Complementation studies in yeast confirmed the deleterious effect of the mutations in these patients. De Lonlay et al. ...