ORPHA:415
Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome
Synonyms: HHH syndrome · ORNT1 deficiency · Ornithine carrier deficiency · Ornithine translocase deficiency · Triple H syndrome
- Type
- Disease
- Group
- Disorder
- Inheritance
- Autosomal recessive
- Age of onset
- Adolescent, Adult, Childhood, Infancy, Neonatal
- Status
- active
A rare, genetic disorder of urea cycle metabolism characterized by either a neonatal-onset with manifestations of lethargy, poor feeding, vomiting and tachypnea or, more commonly, presentations in infancy, childhood or adulthood with chronic neurocognitive deficits, acute encephalopathy and/or coagulation defects or other chronic liver dysfunction.
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Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome | HHH syndrome · ORNT1 deficiency · Ornithine carrier deficiency · Ornithine translocase deficiency · Triple H syndrome |
| fr | Syndrome d'hyperornithinémie-hyperammoniémie-homocitrullinurie | Déficit en ORNT1 · Déficit en ornithine translocase · Syndrome HHH · Syndrome triple H |
| de | Hyperornithinämie-Hyperammonämie-Homocitrullinurie-Syndrom | HHH-Syndrom · ORNT1-Defizienz · ORNT1-Mangel · Ornithin-Translokase-Mangel · Ornithin-Transporter-Mangel · Triple-H-Syndrom |
| es | Síndrome de hiperornitinemia-hiperamonemia-homocitrulinuria | Deficiencia de ORNT1 · Deficiencia de ornitina translocasa · Deficiencia del transportador de la ornitina · Síndrome HHH · Síndrome de la triple H |
| it | Sindrome iperornitinemia iperammoniemia-omocitrullinuria | Deficit del trasportatore dell'ornitina · Deficit di ORNT1 · Sindrome HHH · Sindrome della tripla H |
| nl | Hyperornithinemie - hyperammoniëmie - homocitrullinurie-syndroom | HHH-syndroom · ORNT1-deficiëntie · Ornithinetranslocase-deficiëntie · Ornithinetransporterdeficiëntie · Triple H-syndroom |
| pt | Síndrome de hiperornitinemia-hiperamoniemia-homocitrulinuria | Síndrome HHH · Síndrome de triplo H |
| pl | Zespół hiperornitynemii, hiperamonemii i homocytrulinemii | Niedobór nośnika ornityny · Niedobór ORNT1 · Zespół HHH · Zespół potrójnego H |
| cs | Syndrom zahrnující hyperornitinemii, hyperamonemii a homocitrulinurii | HHH syndrom · Deficit ORNT1 · Triple H syndrom · Deficit přenašeče ornitinu |
| uk | Синдром гіперорнітинемії-гіперамоніємії-гомоцитрулінурії | Синдром HHH · Дефіцит носія орнітину · Дефіцит орнітинової транслокази · Дефіцит ORNT1 · Синдром потрійного Н |
| zh | 高鸟氨酸血症-高氨血症-高瓜氨酸尿综合征 | 鸟氨酸移位酶缺乏症 |
| tr | Hiperornitinemi-hiperamonemi-homositrülinüri sendromu | HHH sendromu · ORNT1 eksikliği · Üçlü H sendromu · Ornitin taşıyıcı eksikliği · Ornitin translokaz eksikliği |
Definition in:
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Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 238970 | E | validated | |
| ICD-10 | E72.4 | NTBT | attributed | validated |
| ICD-11 | 5C50.AY | NTBT | index | validated |
| MONDO | 0009393 | E | validated | |
| MeSH | C538380 | E | validated | |
| UMLS | C0268540 | E | validated | |
| GARD | 2830 | E | validated | |
| MedDRA | 10084220 | E | validated |
E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.
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Classification
Preferential parent (Orphanet linearisation):
Parents in the classifications (3):
- ORPHA:79167Disorder of urea cycle metabolism and ammonia detoxification
rare inborn errors of metabolism; rare genetic diseases - ORPHA:68385Neurometabolic disease
rare genetic diseases; rare neurological diseases - ORPHA:611314Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome
rare genetic diseases; rare neurological diseases
No children.
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Genes
1 direct| Gene | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|
| SLC25A15 | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:10985 | ENSG00000102743 | 603861 | 13q14.11 | solute carrier family 25 member 15 | 22649802[PMID] |
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Prevalence and incidence
4 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Point prevalence | Unknown | — | Worldwide | Class only | Validated | ORPHANET_25874378[PMID] |
| Point prevalence | <1 / 1 000 000 | — | Europe | Class only | Validated | European Medicines Agency 2013[OTHER] |
| Cases/families | 111 cases | Worldwide | Case(s) | Validated | 25874378[PMID] | |
| Prevalence at birth | <1 / 1 000 000 | — | United States | Class only | Validated | 23972786[PMID] |
Value is Orphadata's ValMoy: the mean estimate per 100 000 for prevalence and incidence, the number of cases or families for case reports.
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HPO phenotypes
40 annotations · validated 2019-04-08| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Very frequent (99-80%) | ||
| HP:0011965 | Abnormality of citrulline metabolism | |
| HP:0100543 | Cognitive impairment | |
| HP:0001987 | Hyperammonemia | |
| HP:0012026 | Hyperornithinemia | |
| HP:0001347 | Hyperreflexia | |
| HP:0012758 | Neurodevelopmental delay | |
| Frequent (79-30%) | ||
| HP:0007256 | Abnormal pyramidal sign | |
| HP:0006846 | Acute encephalopathy | |
| HP:0002120 | Cerebral cortical atrophy | |
| HP:0002169 | Clonus | |
| HP:0001289 | Confusion | |
| HP:0001410 | Decreased liver function | |
| HP:0002910 | Elevated circulating hepatic transaminase concentration | |
| HP:0002572 | Episodic vomiting | |
| HP:0001508 | Failure to thrive | |
| HP:0011968 | Feeding difficulties | |
| HP:0001290 | Generalized hypotonia | |
| HP:0012115 | Hepatitis | |
| HP:0002240 | Hepatomegaly | |
| HP:0002495 | Impaired vibratory sensation | |
| HP:0001249 | Intellectual disability | |
| HP:0001254 | Lethargy | |
| HP:0003218 | Oroticaciduria | |
| HP:0002370 | Poor coordination | |
| HP:0002073 | Progressive cerebellar ataxia | |
| HP:0002038 | Protein avoidance | |
| HP:0001258 | Spastic paraplegia | |
| HP:0001328 | Specific learning disability | |
| HP:0011098 | Speech apraxia | |
| HP:0002789 | Tachypnea | |
| Occasional (29-5%) | ||
| HP:0003256 | Abnormality of the coagulation cascade | |
| HP:0001259 | Coma | |
| HP:0002123 | Generalized myoclonic seizure | |
| HP:0007052 | Multifocal cerebral white matter abnormalities | |
| HP:0001950 | Respiratory alkalosis | |
| HP:0001250 | Seizure | |
| HP:0002064 | Spastic gait | |
| Very rare (<4-1%) | ||
| HP:0000533 | Chorioretinal atrophy | |
| HP:0040030 | Chorioretinal hypopigmentation | |
| HP:0001399 | Hepatic failure | |
Run the differential on the 6 obligate / very frequent terms
Annotation source: 18978333[PMID]_11552031[PMID]_25874378[PMID]_22642880[PMID]_3116497[PMID]_5782534[PMID]
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Sources for this card
- Orphanet page: orpha.net/en/disease/detail/415
- This record as JSON: /data/d/415.json