HIBCHD
MCID: 3HY010
MIFTS: 33

3-Hydroxyisobutyryl-Coa Hydrolase Deficiency (HIBCHD)

Categories: Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency

MalaCards integrated aliases for 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency:

Name: 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency 57 20
Methacrylic Aciduria 57 20 58 72 36
Beta-Hydroxyisobutyryl-Coa Deacylase Deficiency 20 29 6 39
Valine Metabolic Defect 57 20 58 72
Hibch Deficiency 57 20 58 72
Beta-Hydroxyisobutyryl Coa Deacylase Deficiency 57 72 70
3-Hydroxyisobutryl-Coa Hydrolase Deficiency 57 72 13
Methacrylic Acid Toxicity 57 20 72
Neurodegeneration Due to 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency 20 58
Hibchd 57 72
Deficiency of Beta-Hydroxyisobutyryl Coa Deacylase 72

Characteristics:

Orphanet epidemiological data:

58
neurodegeneration due to 3-hydroxyisobutyryl-coa hydrolase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide);

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
variable features


HPO:

31
3-hydroxyisobutyryl-coa hydrolase deficiency:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency

GARD : 20 HIBCH deficiency is a rare metabolic disease. Early symptoms include poor muscle tone, poor feeding, seizures, and a gradual loss of skills. HIBCH deficiency can cause signs and symptoms similar to another disease, called Leigh syndrome. Diagnosis is aided by blood tests which show high levels of lactic acid, and imaging studies which show changes in the "globi pallidi" structure of the brain. HIBCH deficiency occurs when a person inherits a mutation in both copies of their HIBCH gene. This pattern of inheritance is called " autosomal recessive." The HIBCH gene tells the body how to make an enzyme called 3-hyroxyisobutyryl-CoA hydrolase. When the body does not have enough working enzyme, it can not break down the amino acid valine. As a result, toxic valine metabolites build up in the body. More specifically, these toxic metabolites build up within the mitochondria of the body's cells. Currently, there is not a cure for HIBCH deficiency. Children with HIBCH deficiency require a multidisciplinary team of doctors who can assess how the deficiency is affecting each body system and recommend appropriate treatments.

MalaCards based summary : 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency, also known as methacrylic aciduria, is related to dystonia and organic acidemia, and has symptoms including seizures, ataxia and myoclonus. An important gene associated with 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency is HIBCH (3-Hydroxyisobutyryl-CoA Hydrolase), and among its related pathways/superpathways is Valine, leucine and isoleucine degradation. Related phenotypes are vomiting and motor delay

OMIM® : 57 3-Hydroxyisobutyryl-CoA hydrolase deficiency is an autosomal recessive inborn error of metabolism characterized by severely delayed psychomotor development, neurodegeneration, increased lactic acid, and brain lesions in the basal ganglia (summary by Ferdinandusse et al., 2013). (250620) (Updated 05-Apr-2021)

KEGG : 36 Methacrylic aciduria is a very rare cerebral organic aciduria caused by 3-Hydroxy-isobutyryl-CoA hydrolase (HIBCH) mutations. HIBCH is a mitochondrial enzyme of valine catabolism. Patients demonstrated delayed development of motor skills, hypotonia, initial poor feeding, and a deterioration in neurological function during the first stages of life.

UniProtKB/Swiss-Prot : 72 3-hydroxyisobutryl-CoA hydrolase deficiency: An autosomal recessive inborn error of valine metabolism. It causes severely delayed psychomotor development, neurodegeneration, increased lactic acid, and brain lesions in the basal ganglia.

Related Diseases for 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency

Diseases related to 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 17)
# Related Disease Score Top Affiliating Genes
1 dystonia 10.4
2 organic acidemia 10.3
3 paroxysmal dystonia 10.3
4 3-hydroxyisobutyric aciduria 10.1
5 leigh syndrome 10.1
6 chromosome 2q35 duplication syndrome 10.0
7 ataxia and polyneuropathy, adult-onset 10.0
8 chorea, childhood-onset, with psychomotor retardation 10.0
9 autosomal recessive disease 10.0
10 hemidystonia 10.0
11 choreatic disease 10.0
12 movement disease 10.0
13 basal ganglia disease 10.0
14 pathologic nystagmus 10.0
15 mitochondrial disorders 10.0
16 athetosis 10.0
17 hypotonia 10.0

Graphical network of the top 20 diseases related to 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency:



Diseases related to 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency

Symptoms & Phenotypes for 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency

Human phenotypes related to 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency:

58 31 (show all 42)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 vomiting 58 31 hallmark (90%) Very frequent (99-80%) HP:0002013
2 motor delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001270
3 dystonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001332
4 progressive neurologic deterioration 58 31 hallmark (90%) Very frequent (99-80%) HP:0002344
5 hypotonia 31 hallmark (90%) HP:0001252
6 hyperreflexia 58 31 frequent (33%) Frequent (79-30%) HP:0001347
7 failure to thrive 58 31 frequent (33%) Frequent (79-30%) HP:0001508
8 sleep disturbance 58 31 frequent (33%) Frequent (79-30%) HP:0002360
9 nystagmus 58 31 frequent (33%) Frequent (79-30%) HP:0000639
10 abnormal vertebral morphology 58 31 frequent (33%) Frequent (79-30%) HP:0003468
11 strabismus 58 31 frequent (33%) Frequent (79-30%) HP:0000486
12 epicanthus 58 31 frequent (33%) Frequent (79-30%) HP:0000286
13 ventriculomegaly 58 31 frequent (33%) Frequent (79-30%) HP:0002119
14 increased serum lactate 58 31 frequent (33%) Frequent (79-30%) HP:0002151
15 aplasia/hypoplasia of the corpus callosum 58 31 frequent (33%) Frequent (79-30%) HP:0007370
16 infantile spasms 58 31 frequent (33%) Frequent (79-30%) HP:0012469
17 feeding difficulties 58 31 frequent (33%) Frequent (79-30%) HP:0011968
18 metabolic acidosis 58 31 frequent (33%) Frequent (79-30%) HP:0001942
19 hypsarrhythmia 58 31 frequent (33%) Frequent (79-30%) HP:0002521
20 abnormality of mitochondrial metabolism 58 31 frequent (33%) Frequent (79-30%) HP:0003287
21 truncal ataxia 58 31 frequent (33%) Frequent (79-30%) HP:0002078
22 facial shape deformation 58 31 frequent (33%) Frequent (79-30%) HP:0011334
23 respiratory insufficiency 58 31 occasional (7.5%) Occasional (29-5%) HP:0002093
24 cryptorchidism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000028
25 irritability 58 31 occasional (7.5%) Occasional (29-5%) HP:0000737
26 encephalopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001298
27 leukoencephalopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0002352
28 small basal ganglia 58 31 occasional (7.5%) Occasional (29-5%) HP:0012697
29 tetralogy of fallot 58 31 very rare (1%) Very rare (<4-1%) HP:0001636
30 head titubation 58 31 very rare (1%) Very rare (<4-1%) HP:0002599
31 seizures 58 Frequent (79-30%)
32 agenesis of corpus callosum 31 HP:0001274
33 muscular hypotonia 58 Very frequent (99-80%)
34 developmental regression 31 HP:0002376
35 global developmental delay 31 HP:0001263
36 abnormal facial shape 31 HP:0001999
37 aminoaciduria 31 HP:0003355
38 myoclonus 31 HP:0001336
39 dysmetria 31 HP:0001310
40 abnormality of the vertebral column 31 HP:0000925
41 generalized hypotonia 31 HP:0001290
42 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
ataxia
developmental regression
myoclonus
dysmetria
more
Abdomen Gastrointestinal:
persistent vomiting
poor feeding

Head And Neck Head:
head titubations (1 patient)

Cardiovascular Heart:
tetralogy of fallot (1 patient)

Head And Neck Eyes:
nystagmus
strabismus
epicanthal folds

Muscle Soft Tissue:
hypotonia
secondarily decreased activities of mitochondrial respiratory enzymes (in some patients)

Head And Neck Face:
dysmorphic facial features (in some patients)

Laboratory Abnormalities:
increased lactate
increased hydroxy-c4-carnitine
urinary excretion of cysteine and cysteamine conjugates of methacrylic acid

Clinical features from OMIM®:

250620 (Updated 05-Apr-2021)

UMLS symptoms related to 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency:


seizures; ataxia; myoclonus; persistent vomiting

Drugs & Therapeutics for 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency

Search Clinical Trials , NIH Clinical Center for 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency

Genetic Tests for 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency

Genetic tests related to 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency:

# Genetic test Affiliating Genes
1 Beta-Hydroxyisobutyryl-Coa Deacylase Deficiency 29 HIBCH

Anatomical Context for 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency

Publications for 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency

Articles related to 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency:

(show all 13)
# Title Authors PMID Year
1
beta-hydroxyisobutyryl coenzyme A deacylase deficiency: a defect in valine metabolism associated with physical malformations. 57 20 6
7122152 1982
2
Metabolite studies in HIBCH and ECHS1 defects: Implications for screening. 57 6 61
26163321 2015
3
HIBCH deficiency in a patient with phenotypic characteristics of mitochondrial disorders. 61 57 6
25251209 2014
4
Mutations in the gene encoding 3-hydroxyisobutyryl-CoA hydrolase results in progressive infantile neurodegeneration. 6 57 61
17160907 2007
5
Successful diagnosis of HIBCH deficiency from exome sequencing and positive retrospective analysis of newborn screening cards in two siblings presenting with Leigh's disease. 6 57
26026795 2015
6
HIBCH mutations can cause Leigh-like disease with combined deficiency of multiple mitochondrial respiratory chain enzymes and pyruvate dehydrogenase. 57 6
24299452 2013
7
Identification of HIBCH gene mutations causing autosomal recessive Leigh syndrome: a gene involved in valine metabolism. 6
25591832 2015
8
Recurrent de novo BICD2 mutation associated with arthrogryposis multiplex congenita and bilateral perisylvian polymicrogyria. 20
27751653 2016
9
A therapeutic regimen for 3-hydroxyisobutyryl-CoA hydrolase deficiency with exercise-induced dystonia. 61
31679561 2019
10
Case report and novel treatment of an autosomal recessive Leigh syndrome caused by short-chain enoyl-CoA hydratase deficiency. 61
30848071 2019
11
3-Hydroxyisobutyryl-CoA hydrolase deficiency in an Iranian child with novel HIBCH compound heterozygous mutations. 61
30847210 2019
12
[Diagnosis and treatment of 3-hydroxyisobutyryl-CoA hydrolase deficiency: a case report and literature review]. 61
30111474 2018
13
Thiamine-Responsive and Non-responsive Patients with PDHC-E1 Deficiency: A Retrospective Assessment. 61
24718837 2015

Variations for 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency

ClinVar genetic disease variations for 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency:

6 (show all 40)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 HIBCH NM_014362.4(HIBCH):c.220-9T>G SNV Pathogenic 1144 rs786200864 GRCh37: 2:191159365-191159365
GRCh38: 2:190294639-190294639
2 HIBCH NM_014362.4(HIBCH):c.79-3C>G SNV Pathogenic 1146 rs778922921 GRCh37: 2:191161682-191161682
GRCh38: 2:190296956-190296956
3 HIBCH NM_014362.4(HIBCH):c.950G>A (p.Gly317Glu) SNV Pathogenic 187864 rs786204004 GRCh37: 2:191077743-191077743
GRCh38: 2:190213017-190213017
4 HIBCH NM_014362.4(HIBCH):c.129dup (p.Gly44fs) Duplication Pathogenic 208531 rs767597690 GRCh37: 2:191161628-191161629
GRCh38: 2:190296902-190296903
5 HIBCH NM_014362.4(HIBCH):c.1033G>A (p.Gly345Ser) SNV Pathogenic 208532 rs770114459 GRCh37: 2:191073618-191073618
GRCh38: 2:190208892-190208892
6 HIBCH NM_014362.4(HIBCH):c.517+1G>A SNV Pathogenic 689764 rs1021805910 GRCh37: 2:191125881-191125881
GRCh38: 2:190261155-190261155
7 HIBCH NM_014362.4(HIBCH):c.609del (p.Gly204fs) Deletion Pathogenic 654855 rs776592661 GRCh37: 2:191116942-191116942
GRCh38: 2:190252216-190252216
8 HIBCH NM_014362.4(HIBCH):c.835G>T (p.Glu279Ter) SNV Pathogenic 972925 GRCh37: 2:191109669-191109669
GRCh38: 2:190244943-190244943
9 HIBCH NM_014362.4(HIBCH):c.763C>T (p.Arg255Ter) SNV Pathogenic 973483 GRCh37: 2:191110926-191110926
GRCh38: 2:190246200-190246200
10 HIBCH NM_014362.4(HIBCH):c.856C>T (p.Gln286Ter) SNV Pathogenic 1033288 GRCh37: 2:191109648-191109648
GRCh38: 2:190244922-190244922
11 HIBCH NM_014362.4(HIBCH):c.852del (p.Leu284fs) Deletion Likely pathogenic 430547 rs1131692017 GRCh37: 2:191109652-191109652
GRCh38: 2:190244926-190244926
12 HIBCH NM_014362.4(HIBCH):c.830T>A (p.Val277Glu) SNV Likely pathogenic 488530 rs1553499757 GRCh37: 2:191109674-191109674
GRCh38: 2:190244948-190244948
13 HIBCH NM_014362.4(HIBCH):c.212A>C (p.Gln71Pro) SNV Likely pathogenic 488531 rs1553506164 GRCh37: 2:191161546-191161546
GRCh38: 2:190296820-190296820
14 HIBCH NM_014362.4(HIBCH):c.809+1G>A SNV Likely pathogenic 424160 rs143746450 GRCh37: 2:191110879-191110879
GRCh38: 2:190246153-190246153
15 HIBCH NM_014362.4(HIBCH):c.457C>T (p.His153Tyr) SNV Likely pathogenic 972924 GRCh37: 2:191125942-191125942
GRCh38: 2:190261216-190261216
16 HIBCH NM_014362.4(HIBCH):c.1128dup (p.Lys377Ter) Duplication Likely pathogenic 217316 rs863225062 GRCh37: 2:191069875-191069876
GRCh38: 2:190205149-190205150
17 HIBCH NM_014362.4(HIBCH):c.365A>G (p.Tyr122Cys) SNV Conflicting interpretations of pathogenicity 1145 rs121918329 GRCh37: 2:191155151-191155151
GRCh38: 2:190290425-190290425
18 HIBCH NM_014362.4(HIBCH):c.410C>T (p.Ala137Val) SNV Uncertain significance 242877 rs1114167288 GRCh37: 2:191152340-191152340
GRCh38: 2:190287614-190287614
19 HIBCH NM_014362.4(HIBCH):c.182C>T (p.Thr61Ile) SNV Uncertain significance 800532 rs1575757363 GRCh37: 2:191161576-191161576
GRCh38: 2:190296850-190296850
20 HIBCH NM_014362.4(HIBCH):c.529G>C (p.Asp177His) SNV Uncertain significance 1031263 GRCh37: 2:191117022-191117022
GRCh38: 2:190252296-190252296
21 HIBCH NM_014362.4(HIBCH):c.763C>G (p.Arg255Gly) SNV Uncertain significance 1033287 GRCh37: 2:191110926-191110926
GRCh38: 2:190246200-190246200
22 HIBCH NM_014362.4(HIBCH):c.353T>C (p.Phe118Ser) SNV Uncertain significance 973469 GRCh37: 2:191155163-191155163
GRCh38: 2:190290437-190290437
23 HIBCH NM_014362.4(HIBCH):c.790C>T (p.His264Tyr) SNV Uncertain significance 973477 GRCh37: 2:191110899-191110899
GRCh38: 2:190246173-190246173
24 HIBCH NM_014362.4(HIBCH):c.238G>C (p.Glu80Gln) SNV Uncertain significance 641906 rs200185893 GRCh37: 2:191159338-191159338
GRCh38: 2:190294612-190294612
25 HIBCH NM_014362.4(HIBCH):c.794T>C (p.Met265Thr) SNV Uncertain significance 642439 rs201049927 GRCh37: 2:191110895-191110895
GRCh38: 2:190246169-190246169
26 HIBCH NM_014362.4(HIBCH):c.196C>T (p.Arg66Trp) SNV Uncertain significance 190268 rs757976755 GRCh37: 2:191161562-191161562
GRCh38: 2:190296836-190296836
27 HIBCH NM_014362.4(HIBCH):c.226G>A (p.Glu76Lys) SNV Uncertain significance 966410 GRCh37: 2:191159350-191159350
GRCh38: 2:190294624-190294624
28 HIBCH NM_014362.4(HIBCH):c.1053T>G (p.Ile351Met) SNV Uncertain significance 664250 rs1575690635 GRCh37: 2:191069951-191069951
GRCh38: 2:190205225-190205225
29 HIBCH NM_014362.4(HIBCH):c.79-7T>C SNV Likely benign 707832 rs201950316 GRCh37: 2:191161686-191161686
GRCh38: 2:190296960-190296960
30 HIBCH NM_014362.4(HIBCH):c.35+10A>C SNV Likely benign 721674 rs747167987 GRCh37: 2:191184432-191184432
GRCh38: 2:190319706-190319706
31 HIBCH NM_014362.4(HIBCH):c.796G>A (p.Asp266Asn) SNV Likely benign 235593 rs144053672 GRCh37: 2:191110893-191110893
GRCh38: 2:190246167-190246167
32 HIBCH NM_014362.4(HIBCH):c.428C>A (p.Thr143Lys) SNV Likely benign 973484 GRCh37: 2:191152322-191152322
GRCh38: 2:190287596-190287596
33 HIBCH NM_014362.4(HIBCH):c.632G>T (p.Gly211Val) SNV Likely benign 973485 GRCh37: 2:191116919-191116919
GRCh38: 2:190252193-190252193
34 HIBCH NM_014362.4(HIBCH):c.957A>G (p.Ser319=) SNV Benign 515763 rs3213841 GRCh37: 2:191077736-191077736
GRCh38: 2:190213010-190213010
35 HIBCH NM_014362.4(HIBCH):c.735A>C (p.Glu245Asp) SNV Benign 382428 rs61752508 GRCh37: 2:191114381-191114381
GRCh38: 2:190249655-190249655
36 HIBCH NM_014362.4(HIBCH):c.488G>C (p.Cys163Ser) SNV Benign 382970 rs74832989 GRCh37: 2:191125911-191125911
GRCh38: 2:190261185-190261185
37 HIBCH NM_014362.4(HIBCH):c.1038T>A (p.Val346=) SNV Benign 383058 rs13406709 GRCh37: 2:191073613-191073613
GRCh38: 2:190208887-190208887
38 HIBCH NM_014362.4(HIBCH):c.243T>G (p.Thr81=) SNV Benign 516906 rs144074606 GRCh37: 2:191159333-191159333
GRCh38: 2:190294607-190294607
39 HIBCH NM_014362.4(HIBCH):c.438+9A>T SNV Benign 386080 rs201813923 GRCh37: 2:191152303-191152303
GRCh38: 2:190287577-190287577
40 HIBCH NM_014362.4(HIBCH):c.214C>T (p.Leu72=) SNV Benign 380559 rs149479887 GRCh37: 2:191161544-191161544
GRCh38: 2:190296818-190296818

UniProtKB/Swiss-Prot genetic disease variations for 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency:

72
# Symbol AA change Variation ID SNP ID
1 HIBCH p.Tyr122Cys VAR_031870 rs121918329

Expression for 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency

Search GEO for disease gene expression data for 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency.

Pathways for 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency

Pathways related to 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency according to KEGG:

36
# Name Kegg Source Accession
1 Valine, leucine and isoleucine degradation hsa00280

GO Terms for 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency

Sources for 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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