MCID: HYP107
MIFTS: 40

Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome

Categories: Genetic diseases, Rare diseases, Metabolic diseases

Aliases & Classifications for Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome

MalaCards integrated aliases for Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome:

Name: Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome 54 25 13
Hhh Syndrome 12 23 50 24 25 56 71 52 69
Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome 23 50 24 25 56 71 29
Ornithine Translocase Deficiency 12 50 25 56 14
Mitochondrial Ornithine Transporter Deficiency 23 24
Triple H Syndrome 25 56
Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome 12
Ornithine Translocase Deficiency Syndrome 50
Ornithine Carrier Deficiency 56
Ornt1 Deficiency 56
Hhhs 50
Hhh 50

Characteristics:

Orphanet epidemiological data:

56
hyperornithinemia-hyperammonemia-homocitrullinuria syndrome
Inheritance: Autosomal recessive; Prevalence: 1-5/10000 (Europe); Age of onset: Adolescent,Adult,Childhood,Infancy,Neonatal; Age of death: infantile;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
phenotypic variability
onset in first months or years of life
increased prevalence in the french-canadian population


HPO:

32
hyperornithinemia-hyperammonemia-homocitrullinemia syndrome:
Onset and clinical course phenotypic variability
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 56  
Inborn errors of metabolism


Summaries for Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome

UniProtKB/Swiss-Prot : 71 Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome: Autosomal recessive disorder resulting in various neurologic symptoms, including mental retardation, spastic paraparesis with pyramidal signs, cerebellar ataxia, and episodic disturbance of consciousness or coma caused by hyperammonemia. It causes a functional impairment of the urea cycle.

MalaCards based summary : Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome, also known as hhh syndrome, is related to saccharopinuria and hypogonadotropic hypogonadism 14 with or without anosmia, and has symptoms including failure to thrive, hepatomegaly and lethargy. An important gene associated with Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome is SLC25A15 (Solute Carrier Family 25 Member 15), and among its related pathways/superpathways are Viral mRNA Translation and Amino Acid metabolism. Affiliated tissues include liver.

Disease Ontology : 12 An amino acid metabolic disorder that has_material_basis in deficiency of ornithine translocase resulting in the accumulation of ammonia in the blood.

Genetics Home Reference : 25 Ornithine translocase deficiency is an inherited disorder that causes ammonia to accumulate in the blood. Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high. The nervous system is especially sensitive to the effects of excess ammonia.

NIH Rare Diseases : 50 this condition doesn't have a summary yet. please see our page(s) on urea cycle disorders.

Wikipedia : 72 Ornithine translocase deficiency, also called hyperornithinemia-hyperammonemia-homocitrullinuria (HHH)... more...

Description from OMIM: 238970
GeneReviews: NBK97260

Related Diseases for Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome

Graphical network of the top 20 diseases related to Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome:



Diseases related to Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome

Symptoms & Phenotypes for Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome

Symptoms via clinical synopsis from OMIM:

54

Growth- Other:
failure to thrive

Abdomen- Liver:
hepatomegaly
liver dysfunction
acute hepatitis

Abdomen- Gastroin testinal:
protein avoidance
episodic vomiting

Hematology:
coagulopathy due to liver dysfunction

Neurologic- Central Nervous System:
hypotonia
hyperreflexia
spasticity
learning disabilities
pyramidal signs
more
Laboratory- Abnormalities:
hyperammonemia
hyperornithinemia
homocitrullinuria

Neurologic- Peripheral Nervous System:
decreased vibration sense (rare)


Clinical features from OMIM:

238970

Human phenotypes related to Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome:

32 (show all 26)
id Description HPO Frequency HPO Source Accession
1 failure to thrive 32 HP:0001508
2 hepatomegaly 32 HP:0002240
3 lethargy 32 HP:0001254
4 global developmental delay 32 HP:0001263
5 hyperammonemia 32 HP:0001987
6 coma 32 HP:0001259
7 intellectual disability 32 frequent (33%) HP:0001249
8 clonus 32 HP:0002169
9 cerebral cortical atrophy 32 HP:0002120
10 spastic paraparesis 32 HP:0002313
11 muscular hypotonia 32 HP:0001252
12 decreased nerve conduction velocity 32 HP:0000762
13 decreased liver function 32 HP:0001410
14 protein avoidance 32 HP:0002038
15 acute encephalopathy 32 HP:0006846
16 chorioretinal atrophy 32 very rare (1%) HP:0000533
17 poor coordination 32 HP:0002370
18 acute hepatitis 32 HP:0200119
19 episodic vomiting 32 HP:0002572
20 hyperornithinemia 32 HP:0012026
21 hypopigmentation of the fundus 32 HP:0007894
22 abnormal pyramidal signs 32 HP:0007256
23 generalized myoclonic seizures 32 HP:0002123
24 specific learning disability 32 HP:0001328
25 impaired vibratory sensation 32 HP:0002495
26 morphological abnormality of the pyramidal tract 32 HP:0002062

UMLS symptoms related to Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome:


clonus, lethargy, muscle spasticity, seizures, paraparesis, spastic, abnormal pyramidal signs

Drugs & Therapeutics for Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome

Search Clinical Trials , NIH Clinical Center for Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome

Genetic Tests for Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome

Genetic tests related to Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome:

id Genetic test Affiliating Genes
1 Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome 29 24 SLC25A15

Anatomical Context for Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome

MalaCards organs/tissues related to Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome:

39
Liver

Publications for Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome

Variations for Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome:

71 (show all 14)
id Symbol AA change Variation ID SNP ID
1 SLC25A15 p.Gly27Glu VAR_012757
2 SLC25A15 p.Gly27Arg VAR_012758 rs104894430
3 SLC25A15 p.Pro126Arg VAR_012759
4 SLC25A15 p.Glu180Lys VAR_012760 rs104894424
5 SLC25A15 p.Gly190Asp VAR_012762 rs202247804
6 SLC25A15 p.Arg275Gln VAR_012764 rs104894431
7 SLC25A15 p.Met37Arg VAR_058948 rs121908533
8 SLC25A15 p.Leu71Gln VAR_058950 rs121908534
9 SLC25A15 p.Gly113Cys VAR_058951 rs199894905
10 SLC25A15 p.Phe188Leu VAR_058952 rs141028076
11 SLC25A15 p.Gly216Ser VAR_058953
12 SLC25A15 p.Thr272Ile VAR_058954 rs121908535
13 SLC25A15 p.Met273Lys VAR_058955 rs202247808
14 SLC25A15 p.Leu283Phe VAR_058956 rs202247809

ClinVar genetic disease variations for Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome:

6 (show all 17)
id Gene Variation Type Significance SNP ID Assembly Location
1 SLC25A15 NM_014252.3(SLC25A15): c.562_564delTTC (p.Phe188del) deletion Pathogenic rs202247803 GRCh37 Chromosome 13, 41381539: 41381541
2 SLC25A15 NM_014252.3(SLC25A15): c.538G> A (p.Glu180Lys) single nucleotide variant Pathogenic rs104894424 GRCh37 Chromosome 13, 41381515: 41381515
3 SLC25A15 NM_014252.3(SLC25A15): c.535C> T (p.Arg179Ter) single nucleotide variant Pathogenic rs104894429 GRCh37 Chromosome 13, 41381512: 41381512
4 SLC25A15 NM_014252.3(SLC25A15): c.79G> A (p.Gly27Arg) single nucleotide variant Pathogenic rs104894430 GRCh37 Chromosome 13, 41373216: 41373216
5 SLC25A15 NM_014252.3(SLC25A15): c.824G> A (p.Arg275Gln) single nucleotide variant Pathogenic rs104894431 GRCh37 Chromosome 13, 41383721: 41383721
6 SLC25A15 NM_014252.3(SLC25A15): c.110T> G (p.Met37Arg) single nucleotide variant Pathogenic rs121908533 GRCh37 Chromosome 13, 41373247: 41373247
7 SLC25A15 NM_014252.3(SLC25A15): c.212T> A (p.Leu71Gln) single nucleotide variant Pathogenic rs121908534 GRCh37 Chromosome 13, 41373349: 41373349
8 SLC25A15 NM_014252.3(SLC25A15): c.815C> T (p.Thr272Ile) single nucleotide variant Pathogenic rs121908535 GRCh37 Chromosome 13, 41383712: 41383712
9 SLC25A15 NM_014252.3(SLC25A15): c.95C> G (p.Thr32Arg) single nucleotide variant Pathogenic rs121908536 GRCh37 Chromosome 13, 41373232: 41373232
10 SLC25A15 NM_014252.3(SLC25A15): c.337G> T (p.Gly113Cys) single nucleotide variant Pathogenic rs199894905 GRCh37 Chromosome 13, 41379276: 41379276
11 SLC25A15 NM_014252.3(SLC25A15): c.44C> A (p.Ala15Glu) single nucleotide variant Pathogenic rs202247806 GRCh37 Chromosome 13, 41367406: 41367406
12 SLC25A15 NM_014252.3(SLC25A15): c.564C> G (p.Phe188Leu) single nucleotide variant Pathogenic rs141028076 GRCh37 Chromosome 13, 41381541: 41381541
13 SLC25A15 NM_014252.3(SLC25A15): c.569G> A (p.Gly190Asp) single nucleotide variant Pathogenic rs202247804 GRCh37 Chromosome 13, 41381546: 41381546
14 SLC25A15 NM_014252.3(SLC25A15): c.658G> A (p.Gly220Arg) single nucleotide variant Pathogenic rs202247805 GRCh37 Chromosome 13, 41382609: 41382609
15 SLC25A15 NM_014252.3(SLC25A15): c.818T> A (p.Met273Lys) single nucleotide variant Pathogenic rs202247808 GRCh37 Chromosome 13, 41383715: 41383715
16 SLC25A15 NM_014252.3(SLC25A15): c.823C> T (p.Arg275Ter) single nucleotide variant Pathogenic rs202247807 GRCh37 Chromosome 13, 41383720: 41383720
17 SLC25A15 NM_014252.3(SLC25A15): c.847C> T (p.Leu283Phe) single nucleotide variant Pathogenic rs202247809 GRCh37 Chromosome 13, 41383744: 41383744

Expression for Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome

Search GEO for disease gene expression data for Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome.

Pathways for Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome

Pathways related to Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1
Show member pathways
12.84 AASS OAT OTC SLC25A15 SLC25A2 SLC6A8
2 11.11 OAT OTC
3
Show member pathways
10 OAT OTC

GO Terms for Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome

Cellular components related to Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 mitochondrial matrix GO:0005759 9.33 AASS OAT OTC
2 mitochondrial inner membrane GO:0005743 9.26 OTC SLC25A15 SLC25A2 SLC25A29
3 mitochondrion GO:0005739 9.23 AASS CLIC1 LIG3 OAT OTC SLC25A15

Biological processes related to Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 transport GO:0006810 9.77 CLIC1 SLC25A15 SLC25A2 SLC25A29 SLC6A8
2 cellular amino acid biosynthetic process GO:0008652 9.32 OAT OTC
3 mitochondrial ornithine transport GO:0000066 9.26 SLC25A15 SLC25A2
4 L-ornithine transmembrane transport GO:1903352 8.96 SLC25A15 SLC25A2
5 mitochondrial transport GO:0006839 8.85 SLC25A29
6 urea cycle GO:0000050 8.8 OTC SLC25A15 SLC25A2

Molecular functions related to Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 L-ornithine transmembrane transporter activity GO:0000064 8.62 SLC25A15 SLC25A2

Sources for Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
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33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
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42 MeSH
43 MESH via Orphanet
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55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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