3-methylglutaconic aciduria type 1

General Information (adopted from Orphanet):

Synonyms, Signs: MGA, TYPE I
3-&#64
3-&#64
MGCA1
MGA1
METHYLGLUTACONYL-CoA HYDRATASE DEFICIENCY
3-methylglutaconyl-CoA hydratase deficiency
MGA type 1
3MG-CoA hydratase deficiency
MG-CoA-HYDRATASE DEFICIENCY
Number of Symptoms 41
OrphanetNr: 67046
OMIM Id: 250950
ICD-10: E71.1
UMLs: C0342727
C0342728
MeSH:
MedDRA:
Snomed: 237951008

Prevalence, inheritance and age of onset:

Prevalence: 20 cases [Orphanet]
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: Neonatal
Infancy
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: 3-methylglutaconic aciduria
 -Rare genetic disease

Symptom Information: Sort by abundance 

1
 (HPO:0000020) Urinary incontinence 75 / 7739
2
 (HPO:0000252) Microcephaly Occasional [Orphanet] 832 / 7739
3
 (HPO:0000648) Optic atrophy 238 / 7739
4
 (HPO:0001260) Dysarthria 329 / 7739
5
 (HPO:0100543) Cognitive impairment Frequent [Orphanet] 230 / 7739
6
 (HPO:0002121) Absence seizures Frequent [Orphanet] 62 / 7739
7
 (HPO:0001270) Motor delay Frequent [Orphanet] 322 / 7739
8
 (HPO:0002510) Spastic tetraplegia 54 / 7739
9
 (HPO:0001347) Hyperreflexia 363 / 7739
10
 (HPO:0002311) Incoordination 84 / 7739
11
 (HPO:0002373) Febrile seizures 37 / 7739
12
 (HPO:0001250) Seizures Frequent [Orphanet] 1245 / 7739
13
 (HPO:0001332) Dystonia 197 / 7739
14
 (HPO:0007034) Generalized hyperreflexia 33 / 7739
15
 (HPO:0002267) Exaggerated startle response 42 / 7739
16
 (HPO:0002133) Status epilepticus Frequent [Orphanet] 59 / 7739
17
 (HPO:0000736) Short attention span 16 / 7739
18
 (HPO:0001263) Global developmental delay Frequent [Orphanet] 853 / 7739
19
 (HPO:0011097) Epileptic spasms Frequent [Orphanet] 45 / 7739
20
 (HPO:0011147) Typical absence seizures Frequent [Orphanet] 33 / 7739
21
 (HPO:0002305) Athetosis 31 / 7739
22
 (HPO:0001269) Hemiparesis Occasional [Orphanet] occasional [HPO] 51 / 7739
23
 (HPO:0000750) Delayed speech and language development 197 / 7739
24
 (HPO:0001328) Specific learning disability Frequent [Orphanet] 114 / 7739
25
 (HPO:0001249) Intellectual disability Frequent [Orphanet] 1089 / 7739
26
 (HPO:0004374) Hemiplegia/hemiparesis Occasional [Orphanet] 158 / 7739
27
 (HPO:0002066) Gait ataxia 327 / 7739
28
 (HPO:0002301) Hemiplegia Occasional [Orphanet] occasional [HPO] 42 / 7739
29
 (HPO:0001251) Ataxia 413 / 7739
30
 (HPO:0002240) Hepatomegaly Occasional [Orphanet] 467 / 7739
31
 (HPO:0001508) Failure to thrive 454 / 7739
32
 (HPO:0001510) Growth delay 295 / 7739
33
 (HPO:0001942) Metabolic acidosis 81 / 7739
34
 (HPO:0001943) Hypoglycemia Frequent [Orphanet] 131 / 7739
35
 (OMIM) Increased urinary 3-methylglutaconic acid 2 / 7739
36
 (OMIM) Decreased activity of 3-methylglutaconyl-CoA hydratase 1 / 7739
37
 (OMIM) Basal ganglia atrophy, progressive 1 / 7739
38
 (OMIM) Increased urinary hydroxyisovaleric acid 1 / 7739
39
 (HPO:0002059) Cerebral atrophy 171 / 7739
40
 (OMIM) Cerebral atrophy, progressive 4 / 7739
41
 (HPO:0002352) Leukoencephalopathy 32 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Type I MGCA is a rare autosomal recessive disorder of leucine catabolism. The metabolic landmark is urinary excretion of 3-methylglutaconic acid (3-MGA) and its derivatives 3-methylglutaric acid (3-MG) and 3-hydroxyisovaleric acid (3-HIVA). Two main presentations have been described: ...
Clinical Description OMIM Greter et al. (1978) described brother and sister with choreoathetosis, spastic paraparesis, dementia, optic atrophy, and, in the urine, increased amounts of 3-methylglutaric and 3-methylglutaconic acids. The excretion was increased by leucine loading. 3-Methylglutaconic acid is known to ...
Molecular genetics OMIM By mutation analysis of the AUH gene in 2 patients with 3-methylglutaconyl aciduria type I, Ijlst et al. (2002) identified a nonsense mutation (600529.0001) and a splice site mutation (600529.0002).

In the patient reported by Shoji ...