Ethylmalonic encephalopathy

General Information (adopted from Orphanet):

Synonyms, Signs: EE
Number of Symptoms 29
OrphanetNr: 51188
OMIM Id: 602473
ICD-10: G31.8
UMLs: C1865349
MeSH: C535737
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 40 cases [Orphanet]
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: Neonatal
Infancy
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: AARSKOG SYNDROME, AUTOSOMAL DOMINANT
 -AARSKOG SYNDROME, AUTOSOMAL DOMINANT
Unspecified mitochondrial disorder
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare neurologic disease

Symptom Information: Sort by abundance 

1
 (HPO:0003219) Ethylmalonic aciduria 5 / 7739
2
 (HPO:0008046) Abnormality of the retinal vasculature 41 / 7739
3
 (HPO:0007256) Abnormal pyramidal signs 116 / 7739
4
 (HPO:0001251) Ataxia 413 / 7739
5
 (HPO:0001249) Intellectual disability 1089 / 7739
6
 (HPO:0001250) Seizures 1245 / 7739
7
 (HPO:0001298) Encephalopathy 72 / 7739
8
 (HPO:0002376) Developmental regression 74 / 7739
9
 (HPO:0002071) Abnormality of extrapyramidal motor function 76 / 7739
10
 (HPO:0001263) Global developmental delay 853 / 7739
11
 (HPO:0002028) Chronic diarrhea 51 / 7739
12
 (HPO:0001508) Failure to thrive 454 / 7739
13
 (HPO:0000967) Petechiae 26 / 7739
14
 (HPO:0003128) Lactic acidosis 116 / 7739
15
 (HPO:0001324) Muscle weakness 859 / 7739
16
 (HPO:0010547) Muscle flaccidity 466 / 7739
17
 (HPO:0001252) Muscular hypotonia 990 / 7739
18
 (HPO:0003688) Decreased activity of cytochrome C oxidase in muscle tissue 20 / 7739
19
 (HPO:0008947) Infantile muscular hypotonia 482 / 7739
20
 (OMIM) Increased urinary thiosulphate 1 / 7739
21
 (OMIM) Increased serum C4 and C5 acylcarnitine esters 1 / 7739
22
 (OMIM) Methylsuccinic aciduria 2 / 7739
23
 (OMIM) Cytochrome c oxidase deficiency in skeletal muscle and brain 1 / 7739
24
 (OMIM) Increased urinary isobutyryl glycine 1 / 7739
25
 (OMIM) Orthostatic acrocyanosis 1 / 7739
26
 (OMIM) Retinal lesions with tortuous vessels 1 / 7739
27
 (HPO:0007183) Focal T2 hyperintense basal ganglia lesion 6 / 7739
28
 (HPO:0000007) Autosomal recessive inheritance 2538 / 7739
29
 (OMIM) Increased urinary 2-methylbutyryl glycine 1 / 7739

Associated genes:

ETHE1;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Ethylmalonic encephalopathy is an autosomal recessive severe metabolic disorder of infancy affecting the brain, gastrointestinal tract, and peripheral vessels. The disorder is characterized by neurodevelopmental delay and regression, prominent pyramidal and extrapyramidal signs, recurrent petechiae, orthostatic acrocyanosis, and chronic ...
Clinical Description OMIM Burlina et al. (1991) first described ethylmalonic encephalopathy as a syndrome characterized by developmental delay, acrocyanosis, petechiae, and chronic diarrhea. Laboratory studies showed ethylmalonic and methylsuccinic aciduria and lactic acidemia. However, in vitro activities of short chain acyl-CoA dehydrogenase ...
Molecular genetics OMIM By a combination of homozygosity mapping, integration of physical and functional genomic datasets, and mutational screening, Tiranti et al. (2004) identified the ETHE1 gene (608451) as the site of mutations causing EE. They demonstrated that the ETHE1 protein is ...
Population genetics OMIM With few exceptions the patients with ethylmalonic encephalopathy have been of Mediterranean (Garcia-Silva et al., 1997; Grosso et al., 2002) or Arabic (Ozand et al., 1994) extraction.