MCID: HSD004
MIFTS: 30

Hsd10 Mitochondrial Disease

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

Aliases & Classifications for Hsd10 Mitochondrial Disease

MalaCards integrated aliases for Hsd10 Mitochondrial Disease:

Name: Hsd10 Mitochondrial Disease 57
2-Methyl-3-Hydroxybutyryl-Coa Dehydrogenase Deficiency 57 59 75
17-Beta-Hydroxysteroid Dehydrogenase X Deficiency 57 75 13
Mhbd Deficiency 57 59 75
Mental Retardation with Chorioathetosis and Abnormal Behavior 57 75
3-Hydroxyacyl-Coa Dehydrogenase Ii Deficiency 57 75
2-Methyl-3-Hydroxybutyric Aciduria 59 73
Hsd17b10 Deficiency 57 75
Hsd10md 57 75
Mrxs10 57 75
Camr 57 75
X-Linked Intellectual Disability-Choreoathetosis-Abnormal Behavior Syndrome 59
2-Methyl-3-Hydroxybutyryl-Coa Dehydrogenase Deficiency, Infantile Type 59
2-Methyl-3-Hydroxybutyryl-Coa Dehydrogenase Deficiency, Neonatal Type 59
2-Methyl-3-Hydroxybutyryl-Coa Dehydrogenase Deficiency, Classic Type 59
Chorioathetosis with Mental Retardation and Abnormal Behavior; Camr 57
Chorioathetosis with Mental Retardation and Abnormal Behavior 57
2-Methyl-3-Hydroxybutyryl-Coa Dehydrogenase Deficiency 37
Mental Retardation, X-Linked, Syndromic 10; Mrxs10 57
Syndromic X-Linked Intellectual Disability Type 10 59
2-Methyl-3-Hydroxybutyric Aciduria, Infantile Type 59
3-Hydroxyacyl-Coa Dehydrogenase Type Ii Deficiency 75
2-Methyl-3-Hydroxybutyric Aciduria, Neonatal Type 59
3-Hydroxyacyl-Coa Dehydrogenase Type 2 Deficiency 75
3-Hydroxyacyl-Coa Dehydrogenase Type-2 Deficiency 75
Hydroxyacyl-Coa Dehydrogenase, Type 2, Deficiency 73
2-Methyl-3-Hydroxybutyric Aciduria, Classic Type 59
Mental Retardation, X-Linked, Syndromic 10 73
Hsd10 Deficiency, Infantile Type 59
Hsd10 Deficiency, Atypical Type 59
Mhbd Deficiency, Infantile Type 59
Hsd10 Deficiency, Neonatal Type 59
Hsd10 Deficiency, Classic Type 59
Mhbd Deficiency, Neonatal Type 59
Hsd10 Disease, Infantile Type 59
Mhbd Deficiency, Classic Type 59
Hsd10 Disease, Atypical Type 59
Hsd10 Disease, Neonatal Type 59
Hsd10 Disease, Classic Type 59
Hds10 Mitochondrial Disease 75
Hsd10 Deficiency 59
Hsd10 Disease 59

Characteristics:

Orphanet epidemiological data:

59
hsd10 disease
Inheritance: X-linked dominant;
hsd10 disease, infantile type
Inheritance: X-linked dominant; Age of onset: Infancy,Neonatal;
hsd10 disease, neonatal type
Inheritance: X-linked dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;
hsd10 disease, atypical type
Inheritance: X-linked dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

57
Miscellaneous:
highly variable phenotype and severity
age at onset can range from infancy to childhood
less severe phenotype in females
severity of phenotype is not related to residual enzyme activity

Inheritance:
x-linked dominant


HPO:

32
hsd10 mitochondrial disease:
Onset and clinical course phenotypic variability infantile onset
Inheritance x-linked dominant inheritance


Classifications:



Summaries for Hsd10 Mitochondrial Disease

OMIM : 57 HSD10 mitochondrial disease most commonly presents as an X-linked neurodegenerative disorder with highly variable severity and age at onset ranging from the neonatal period to early childhood. The features are usually multisystemic, consistent with mitochondrial dysfunction. Some affected males have a severe infantile form associated with cardiomyopathy that may result in death in early childhood, whereas other rare patients may have juvenile onset or even atypical presentations with normal neurologic development. More severely affected males show developmental regression in infancy or early childhood, often associated with early-onset intractable seizures, progressive choreoathetosis and spastic tetraplegia, optic atrophy or retinal degeneration resulting in visual loss, and mental retardation. Heterozygous females may show non-progressive developmental delay and intellectual disability, but may also be clinically normal. Although the diagnosis can be aided by the observation of increased urinary levels of metabolites of isoleucine breakdown (2-methyl-3 hydroxybutyrate and tiglylglycine), there is not a correlation between these laboratory features and the phenotype. In addition, patients do not develop severe metabolic crises in the neonatal period as observed in other organic acidurias, but may show persistent lactic acidosis, most likely reflecting mitochondrial dysfunction (summary by Rauschenberger et al., 2010; review by Zschocke, 2012). In a review of the disorder, Zschocke (2012) noted that although this disorder was originally thought to be an inborn error of branched-chain fatty acid and isoleucine metabolism resulting from decreased HSD17B10 dehydrogenase activity (HSD17B10 'deficiency'), subsequent studies have shown that the HSD17B10 gene product has additional functions and also acts as a component of the mitochondrial RNase P holoenzyme, which is involved in mitochondrial tRNA processing and maturation and ultimately mitochondrial protein synthesis. The multisystemic features of HSD10MD most likely result from the adverse effect of HSD17B10 mutations on mitochondrial function, rather than from the effects on the dehydrogenase activity (see PATHOGENESIS below). (300438)

MalaCards based summary : Hsd10 Mitochondrial Disease, also known as 2-methyl-3-hydroxybutyryl-coa dehydrogenase deficiency, is related to 2-methyl-3-hydroxybutyric aciduria and syndromic x-linked intellectual disability type 10, and has symptoms including muscle spasticity, seizures and agitation. An important gene associated with Hsd10 Mitochondrial Disease is HSD17B10 (Hydroxysteroid 17-Beta Dehydrogenase 10), and among its related pathways/superpathways is Valine, leucine and isoleucine degradation. Affiliated tissues include brain, and related phenotypes are intellectual disability and behavioral abnormality

UniProtKB/Swiss-Prot : 75 HDS10 mitochondrial disease: An X-linked multisystemic disorder with highly variable severity. Age at onset ranges from the neonatal period to early childhood. Features include progressive neurodegeneration, psychomotor retardation, loss of mental and motor skills, seizures, cardiomyopathy, and visual and hearing impairment. Some patients manifest lactic acidosis and metabolic acidosis.

Wikipedia : 76 17-β-Hydroxysteroid dehydrogenase X (HSD10) also known as 3-hydroxyacyl-CoA dehydrogenase type-2 is a... more...

Related Diseases for Hsd10 Mitochondrial Disease

Diseases related to Hsd10 Mitochondrial Disease via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 2-methyl-3-hydroxybutyric aciduria 11.4
2 syndromic x-linked intellectual disability type 10 10.9

Symptoms & Phenotypes for Hsd10 Mitochondrial Disease

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
nystagmus
optic atrophy
visual loss
retinal degeneration

Cardiovascular Heart:
hypertrophic cardiomyopathy

Head And Neck Ears:
hearing loss, sensorineural

Metabolic Features:
lactic acidosis (in some patients)
metabolic acidosis (in some patients)

Neurologic Central Nervous System:
intellectual disability
seizures
spasticity
dysarthria
spastic tetraplegia
more
Neurologic Behavioral Psychiatric Manifestations:
agitation
restlessness
aggression

Laboratory Abnormalities:
increased urinary tiglylglycine
patient cells show abnormal mitochondrial morphology
decreased activity of 2-methyl-3-hydroxybutyryl co-a dehydrogenase
increased urinary 2-methyl-3 hydroxybutyrate


Clinical features from OMIM:

300438

Human phenotypes related to Hsd10 Mitochondrial Disease:

59 32 (show all 26)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 59 32 Very frequent (99-80%) HP:0001249
2 behavioral abnormality 59 Very frequent (99-80%)
3 abnormality of movement 59 Very frequent (99-80%)
4 sensorineural hearing impairment 32 HP:0000407
5 retinal degeneration 32 HP:0000546
6 visual loss 32 HP:0000572
7 nystagmus 32 HP:0000639
8 optic atrophy 32 HP:0000648
9 restlessness 32 HP:0000711
10 agitation 32 HP:0000713
11 aggressive behavior 32 HP:0000718
12 delayed speech and language development 32 HP:0000750
13 seizures 32 HP:0001250
14 muscular hypotonia 32 HP:0001252
15 dysarthria 32 HP:0001260
16 global developmental delay 32 HP:0001263
17 choreoathetosis 32 HP:0001266
18 generalized hypotonia 32 HP:0001290
19 hypertrophic cardiomyopathy 32 HP:0001639
20 metabolic acidosis 32 HP:0001942
21 hypoglycemia 32 HP:0001943
22 cerebral cortical atrophy 32 HP:0002120
23 progressive neurologic deterioration 32 HP:0002344
24 developmental regression 32 HP:0002376
25 spastic tetraplegia 32 HP:0002510
26 lactic acidosis 32 HP:0003128

UMLS symptoms related to Hsd10 Mitochondrial Disease:


muscle spasticity, seizures, agitation, unspecified visual loss, restlessness

Drugs & Therapeutics for Hsd10 Mitochondrial Disease

Search Clinical Trials , NIH Clinical Center for Hsd10 Mitochondrial Disease

Genetic Tests for Hsd10 Mitochondrial Disease

Anatomical Context for Hsd10 Mitochondrial Disease

MalaCards organs/tissues related to Hsd10 Mitochondrial Disease:

41
Brain

Publications for Hsd10 Mitochondrial Disease

Articles related to Hsd10 Mitochondrial Disease:

# Title Authors Year
1
Spastic diplegia and periventricular white matter abnormalities in 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency, a defect of isoleucine metabolism: differential diagnosis with hypoxic-ischemic brain diseases. ( 15059617 )
2004
2
2-Methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency: impaired catabolism of isoleucine presenting as neurodegenerative disease. ( 14729408 )
2004
3
2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency is caused by mutations in the HADH2 gene. ( 12696021 )
2003
4
Progressive infantile neurodegeneration caused by 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency: a novel inborn error of branched-chain fatty acid and isoleucine metabolism. ( 11102558 )
2000

Variations for Hsd10 Mitochondrial Disease

UniProtKB/Swiss-Prot genetic disease variations for Hsd10 Mitochondrial Disease:

75 (show all 11)
# Symbol AA change Variation ID SNP ID
1 HSD17B10 p.Leu122Val VAR_015987 rs28935476
2 HSD17B10 p.Arg130Cys VAR_015988 rs28935475
3 HSD17B10 p.Asn247Ser VAR_032093 rs122461163
4 HSD17B10 p.Asp86Gly VAR_078864 rs587777651
5 HSD17B10 p.Gln165His VAR_078865
6 HSD17B10 p.Lys212Glu VAR_078866 rs886041974
7 HSD17B10 p.Glu249Gln VAR_078867 rs62626305
8 HSD17B10 p.Val12Leu VAR_080049
9 HSD17B10 p.Val176Met VAR_080050
10 HSD17B10 p.Pro210Ser VAR_080051
11 HSD17B10 p.Arg226Gln VAR_080052

ClinVar genetic disease variations for Hsd10 Mitochondrial Disease:

6
(show all 20)
# Gene Variation Type Significance SNP ID Assembly Location
1 HSD17B10 NM_001037811.2(HSD17B10): c.388C> T (p.Arg130Cys) single nucleotide variant Pathogenic rs28935475 GRCh37 Chromosome X, 53459034: 53459034
2 HSD17B10 NM_001037811.2(HSD17B10): c.388C> T (p.Arg130Cys) single nucleotide variant Pathogenic rs28935475 GRCh38 Chromosome X, 53432086: 53432086
3 HSD17B10 NM_001037811.2(HSD17B10): c.364C> G (p.Leu122Val) single nucleotide variant Pathogenic rs28935476 GRCh37 Chromosome X, 53459058: 53459058
4 HSD17B10 NM_001037811.2(HSD17B10): c.364C> G (p.Leu122Val) single nucleotide variant Pathogenic rs28935476 GRCh38 Chromosome X, 53432110: 53432110
5 HSD17B10 NM_001037811.2(HSD17B10): c.713A> G (p.Asn238Ser) single nucleotide variant Pathogenic rs122461163 GRCh37 Chromosome X, 53458398: 53458398
6 HSD17B10 NM_001037811.2(HSD17B10): c.713A> G (p.Asn238Ser) single nucleotide variant Pathogenic rs122461163 GRCh38 Chromosome X, 53431450: 53431450
7 HSD17B10 NM_004493.2(HSD17B10): c.574C> A (p.Arg192=) single nucleotide variant Pathogenic rs122462164 GRCh37 Chromosome X, 53458767: 53458767
8 HSD17B10 NM_004493.2(HSD17B10): c.574C> A (p.Arg192=) single nucleotide variant Pathogenic rs122462164 GRCh38 Chromosome X, 53431819: 53431819
9 HSD17B10 NM_001037811.2(HSD17B10): c.718G> C (p.Glu240Gln) single nucleotide variant Pathogenic rs62626305 GRCh37 Chromosome X, 53458393: 53458393
10 HSD17B10 NM_001037811.2(HSD17B10): c.718G> C (p.Glu240Gln) single nucleotide variant Pathogenic rs62626305 GRCh38 Chromosome X, 53431445: 53431445
11 HSD17B10 NM_001037811.2(HSD17B10): c.257A> G (p.Asp86Gly) single nucleotide variant Pathogenic rs587777651 GRCh37 Chromosome X, 53459295: 53459295
12 HSD17B10 NM_001037811.2(HSD17B10): c.257A> G (p.Asp86Gly) single nucleotide variant Pathogenic rs587777651 GRCh38 Chromosome X, 53432347: 53432347
13 HSD17B10 NM_004493.2(HSD17B10): c.218C> G (p.Thr73Arg) single nucleotide variant Uncertain significance rs794729644 GRCh37 Chromosome X, 53459334: 53459334
14 HSD17B10 NM_004493.2(HSD17B10): c.218C> G (p.Thr73Arg) single nucleotide variant Uncertain significance rs794729644 GRCh38 Chromosome X, 53432386: 53432386
15 HSD17B10 NM_004493.2(HSD17B10): c.592C> A (p.Pro198Thr) single nucleotide variant Likely pathogenic rs886037927 GRCh37 Chromosome X, 53458749: 53458749
16 HSD17B10 NM_004493.2(HSD17B10): c.592C> A (p.Pro198Thr) single nucleotide variant Likely pathogenic rs886037927 GRCh38 Chromosome X, 53431801: 53431801
17 HSD17B10 NM_004493.2(HSD17B10): c.634A> G (p.Lys212Glu) single nucleotide variant Pathogenic rs886041974 GRCh37 Chromosome X, 53458504: 53458504
18 HSD17B10 NM_004493.2(HSD17B10): c.634A> G (p.Lys212Glu) single nucleotide variant Pathogenic rs886041974 GRCh38 Chromosome X, 53431556: 53431556
19 HSD17B10 NM_001037811.2(HSD17B10): c.650G> A (p.Arg217Gln) single nucleotide variant Pathogenic GRCh38 Chromosome X, 53431513: 53431513
20 HSD17B10 NM_001037811.2(HSD17B10): c.650G> A (p.Arg217Gln) single nucleotide variant Pathogenic GRCh37 Chromosome X, 53458461: 53458461

Expression for Hsd10 Mitochondrial Disease

Search GEO for disease gene expression data for Hsd10 Mitochondrial Disease.

Pathways for Hsd10 Mitochondrial Disease

Pathways related to Hsd10 Mitochondrial Disease according to KEGG:

37
# Name Kegg Source Accession
1 Valine, leucine and isoleucine degradation hsa00280

GO Terms for Hsd10 Mitochondrial Disease

Sources for Hsd10 Mitochondrial Disease

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
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34 ICD10 via Orphanet
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36 IUPHAR
37 KEGG
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44 MeSH
45 MESH via Orphanet
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49 NCI
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58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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