MCID: 3HY010
MIFTS: 26

3-Hydroxyisobutyryl-Coa Hydrolase Deficiency

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Metabolic 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 53
Methacrylic Aciduria 57 53 59 75 37
Beta-Hydroxyisobutyryl-Coa Deacylase Deficiency 53 29 6 40
Valine Metabolic Defect 57 53 59 75
Hibch Deficiency 57 53 59 75
Beta-Hydroxyisobutyryl Coa Deacylase Deficiency 57 75 73
3-Hydroxyisobutryl-Coa Hydrolase Deficiency 57 75 13
Methacrylic Acid Toxicity 57 53 75
Neurodegeneration Due to 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency 53 59
Hibchd 57 75
Deficiency of Beta-Hydroxyisobutyryl Coa Deacylase 75
3-Hydroxyisobutyryl-Coa Hydrolase 13

Characteristics:

Orphanet epidemiological data:

59
neurodegeneration due to 3-hydroxyisobutyryl-coa hydrolase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide);

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
variable features


HPO:

32
3-hydroxyisobutyryl-coa hydrolase deficiency:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency

NIH Rare Diseases : 53 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 acidvaline. 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 mitochondrial disorders, and has symptoms including ataxia, myoclonus and seizures. 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. Affiliated tissues include brain and testes, and related phenotypes are muscular hypotonia and agenesis of corpus callosum

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)

UniProtKB/Swiss-Prot : 75 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:

# Related Disease Score Top Affiliating Genes
1 mitochondrial disorders 9.9

Symptoms & Phenotypes for 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency

Symptoms via clinical synopsis from OMIM:

57
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 Head:
head titubations (1 patient)

Cardiovascular Heart:
tetralogy of fallot (1 patient)

Neurologic Central Nervous System:
seizures
ataxia
developmental regression
myoclonus
dysmetria
more
Abdomen Gastrointestinal:
poor feeding
persistent vomiting

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

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

59 32 (show all 18)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 muscular hypotonia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001252
2 agenesis of corpus callosum 32 HP:0001274
3 nystagmus 32 HP:0000639
4 seizures 32 HP:0001250
5 developmental regression 32 HP:0002376
6 global developmental delay 32 HP:0001263
7 abnormal facial shape 32 HP:0001999
8 abnormal vertebral morphology 32 HP:0003468
9 aminoaciduria 32 HP:0003355
10 feeding difficulties 32 HP:0011968
11 strabismus 32 HP:0000486
12 epicanthus 32 HP:0000286
13 myoclonus 32 HP:0001336
14 dysmetria 32 HP:0001310
15 dystonia 32 HP:0001332
16 tetralogy of fallot 32 HP:0001636
17 abnormality of the vertebral column 32 HP:0000925
18 generalized hypotonia 32 HP:0001290

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


ataxia, myoclonus, seizures, 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

MalaCards organs/tissues related to 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency:

41
Brain, Testes

Publications for 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency

Articles related to 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency:

# Title Authors Year
1
HIBCH deficiency in a patient with phenotypic characteristics of mitochondrial disorders. ( 25251209 )
2014

Variations for 3-Hydroxyisobutyryl-Coa Hydrolase Deficiency

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

75
# Symbol AA change Variation ID SNP ID
1 HIBCH p.Tyr122Cys VAR_031870 rs121918329

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

6
(show all 24)
# Gene Variation Type Significance SNP ID Assembly Location
1 HIBCH NM_014362.3(HIBCH): c.220-9T> G single nucleotide variant Pathogenic rs786200864 GRCh37 Chromosome 2, 191159365: 191159365
2 HIBCH NM_014362.3(HIBCH): c.220-9T> G single nucleotide variant Pathogenic rs786200864 GRCh38 Chromosome 2, 190294639: 190294639
3 HIBCH NM_014362.3(HIBCH): c.365A> G (p.Tyr122Cys) single nucleotide variant Pathogenic/Likely pathogenic rs121918329 GRCh37 Chromosome 2, 191155151: 191155151
4 HIBCH NM_014362.3(HIBCH): c.365A> G (p.Tyr122Cys) single nucleotide variant Pathogenic/Likely pathogenic rs121918329 GRCh38 Chromosome 2, 190290425: 190290425
5 HIBCH NM_014362.3(HIBCH): c.79-3C> G single nucleotide variant Pathogenic rs778922921 GRCh37 Chromosome 2, 191161682: 191161682
6 HIBCH NM_014362.3(HIBCH): c.79-3C> G single nucleotide variant Pathogenic rs778922921 GRCh38 Chromosome 2, 190296956: 190296956
7 HIBCH NM_014362.3(HIBCH): c.950G> A (p.Gly317Glu) single nucleotide variant Pathogenic rs786204004 GRCh38 Chromosome 2, 190213017: 190213017
8 HIBCH NM_014362.3(HIBCH): c.950G> A (p.Gly317Glu) single nucleotide variant Pathogenic rs786204004 GRCh37 Chromosome 2, 191077743: 191077743
9 HIBCH NM_014362.3(HIBCH): c.196C> T (p.Arg66Trp) single nucleotide variant Uncertain significance rs757976755 GRCh37 Chromosome 2, 191161562: 191161562
10 HIBCH NM_014362.3(HIBCH): c.196C> T (p.Arg66Trp) single nucleotide variant Uncertain significance rs757976755 GRCh38 Chromosome 2, 190296836: 190296836
11 HIBCH NM_014362.3(HIBCH): c.129dupA (p.Gly44Argfs) duplication Pathogenic rs775571897 GRCh38 Chromosome 2, 190296903: 190296903
12 HIBCH NM_014362.3(HIBCH): c.129dupA (p.Gly44Argfs) duplication Pathogenic rs775571897 GRCh37 Chromosome 2, 191161629: 191161629
13 HIBCH NM_014362.3(HIBCH): c.1033G> A (p.Gly345Ser) single nucleotide variant Pathogenic rs770114459 GRCh37 Chromosome 2, 191073618: 191073618
14 HIBCH NM_014362.3(HIBCH): c.1033G> A (p.Gly345Ser) single nucleotide variant Pathogenic rs770114459 GRCh38 Chromosome 2, 190208892: 190208892
15 HIBCH NM_014362.3(HIBCH): c.1128dupT (p.Lys377Terfs) duplication Pathogenic rs863225062 GRCh38 Chromosome 2, 190205150: 190205150
16 HIBCH NM_014362.3(HIBCH): c.1128dupT (p.Lys377Terfs) duplication Pathogenic rs863225062 GRCh37 Chromosome 2, 191069876: 191069876
17 HIBCH NM_014362.3(HIBCH): c.410C> T (p.Ala137Val) single nucleotide variant Pathogenic rs1114167288 GRCh37 Chromosome 2, 191152340: 191152340
18 HIBCH NM_014362.3(HIBCH): c.410C> T (p.Ala137Val) single nucleotide variant Pathogenic rs1114167288 GRCh38 Chromosome 2, 190287614: 190287614
19 HIBCH NM_014362.3(HIBCH): c.809+1G> A single nucleotide variant Pathogenic/Likely pathogenic rs143746450 GRCh37 Chromosome 2, 191110879: 191110879
20 HIBCH NM_014362.3(HIBCH): c.809+1G> A single nucleotide variant Pathogenic/Likely pathogenic rs143746450 GRCh38 Chromosome 2, 190246153: 190246153
21 HIBCH NM_014362.3(HIBCH): c.830T> A (p.Val277Glu) single nucleotide variant Likely pathogenic GRCh37 Chromosome 2, 191109674: 191109674
22 HIBCH NM_014362.3(HIBCH): c.830T> A (p.Val277Glu) single nucleotide variant Likely pathogenic GRCh38 Chromosome 2, 190244948: 190244948
23 HIBCH NM_014362.3(HIBCH): c.212A> C (p.Gln71Pro) single nucleotide variant Likely pathogenic GRCh37 Chromosome 2, 191161546: 191161546
24 HIBCH NM_014362.3(HIBCH): c.212A> C (p.Gln71Pro) single nucleotide variant Likely pathogenic GRCh38 Chromosome 2, 190296820: 190296820

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:

37
# 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

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7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
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69 SNOMED-CT via HPO
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74 UMLS via Orphanet
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