WARS2-related combined oxidative phosphorylation defect
Synonyms: Mitochondrial tryptophanyl-tRNA synthetase deficiency
- Type
- Disease
- Group
- Disorder
- Inheritance
- Autosomal recessive
- Age of onset
- Infancy, Neonatal
- Status
- active
A rare mitochondrial oxidative phosphorylation disorder characterized by a spectrum of three main clinical phenotypes comprising a severe neonatal phenotype with early fatal lactic acidosis, a more protracted course with early-onset developmental delay, motor weakness, extrapyramidal signs, and with or without epilepsy, and a phenotype with normal early development and Parkinson-like symptoms starting around the age of one year. Additional, variably reported, signs and symptoms include cardiomyopathy, optic anomalies, hepatosplenomegaly, and abnormal brain MRI findings, among others. Deficiencies in mitochondrial oxidative phosphorylation enzymes are inconsistent.
Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | WARS2-related combined oxidative phosphorylation defect | Mitochondrial tryptophanyl-tRNA synthetase deficiency |
| fr | Déficit combiné de la phosphorylation oxydative associé à WARS2 | Déficit en tryptophanyl-ARNt synthétase mitochondriale |
| de | Kombinierter Defekt der oxidativen Phosphorylierung, WARS2-assoziierter | Mitochondriale Tryptophanyl-tRNA-Synthetase-Defizienz |
| es | Deficiencia combinada de la fosforilación oxidativa asociada a WARS2 | Deficiencia de triptofanil-ARNt sintetasa mitocondrial |
| it | Difetto combinato della fosforilazione ossidativa correlato a WARS2 | Deficit di triptofanil-tRNA sintetasi mitocondriale |
| nl | WARS2-gerelateerde gecombineerde oxidatieve fosforylatiedeficiëntie | Deficiëntie van mitochondriaal tryptofanyl-tRNA-synthetase |
| pt | Defeito combinado da fosforilação oxidativa WARS2-relacionado | |
| pl | Złożony defekt fosforylacji oksydacyjnej związany z WARS2 | = en |
| cs | WARS2-vázaný kombinovaný defekt oxidativní fosforylace | = en |
| uk | Повязаний з WARS2 комбінований дефект окисного фосфорилювання | Дефіцит мітохондріальної триптофаніл-тРНК-синтетази |
| zh | WARS2相关复合氧化磷酸化缺陷 | 线粒体色氨酰-tRNA合成酶缺乏症 |
| tr | WARS2 ile ilgili kombine oksidatif fosforilasyon defekti | Mitokondriyal triptofanil-tRNA sentetaz eksikliği |
Definition in:
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 617710 | E | validated | |
| ICD-10 | E88.8 | NTBT | attributed | validated |
| ICD-11 | 5C53.2Y | NTBT | attributed | validated |
| MONDO | 0060578 | E | validated | |
| UMLS | C4540192 | E | validated |
E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.
Classification
Preferential parent (Orphanet linearisation):
Parents in the classifications (3):
- ORPHA:35696Mitochondrial disorder due to a defect in mitochondrial protein synthesis
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.
Genes
1 direct| Gene | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|
| WARS2 | Disease-causing germline mutation(s) in | Assessed | HGNC:12730 | ENSG00000116874 | 604733 | 1p12 | tryptophanyl tRNA synthetase 2, mitochondrial | 28236339[PMID]_29783990[PMID] |
Prevalence and incidence
2 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Cases/families | 11 cases | Worldwide | Case(s) | Validated | 29783990[PMID] | |
| Point prevalence | <1 / 1 000 000 | — | Worldwide | Class only | Validated | ORPHANET_29783990[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.
HPO phenotypes
57 annotations · validated 2020-08-28| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Very frequent (99-80%) | ||
| HP:0100022 | Abnormality of movement | |
| HP:0008947 | Floppy infant | |
| HP:0001263 | Global developmental delay | |
| HP:0001249 | Intellectual disability | |
| Frequent (79-30%) | ||
| HP:0012379 | Abnormal enzyme/coenzyme activity | |
| HP:0002518 | Abnormal periventricular white matter morphology | |
| HP:0002167 | Abnormality of speech or vocalization | |
| HP:0000718 | Aggressive behavior | |
| HP:0008936 | Axial hypotonia | |
| HP:0001272 | Cerebellar atrophy | |
| HP:0002059 | Cerebral atrophy | |
| HP:0012430 | Cerebral white matter hypoplasia | |
| HP:0012448 | Delayed myelination | |
| HP:0001288 | Gait disturbance | |
| HP:0003700 | Generalized amyotrophy | |
| HP:0001347 | Hyperreflexia | |
| HP:0002151 | Increased circulating lactate concentration | |
| HP:0002342 | Intellectual disability, moderate | |
| HP:0001511 | Intrauterine growth retardation | |
| HP:0003128 | Lactic acidosis | |
| HP:0002451 | Limb dystonia | |
| HP:0002509 | Limb hypertonia | |
| HP:0001324 | Muscle weakness | |
| HP:0001250 | Seizure | |
| HP:0002119 | Ventriculomegaly | |
| Occasional (29-5%) | ||
| HP:0001999 | Abnormal facial shape | |
| HP:0001344 | Absent speech | |
| HP:0000646 | Amblyopia | |
| HP:0001251 | Ataxia | |
| HP:0002305 | Athetosis | |
| HP:0001638 | Cardiomyopathy | |
| HP:0001320 | Cerebellar vermis hypoplasia | |
| HP:0003698 | Difficulty standing | |
| HP:0002198 | Dilated fourth ventricle | |
| HP:0001310 | Dysmetria | |
| HP:0002015 | Dysphagia | |
| HP:0000577 | Exotropia | |
| HP:0000218 | High palate | |
| HP:0000316 | Hypertelorism | |
| HP:0002365 | Hypoplasia of the brainstem | |
| HP:0007772 | Impaired smooth pursuit | |
| HP:0002187 | Intellectual disability, profound | |
| HP:0006956 | Lateral ventricle dilatation | |
| HP:0002352 | Leukoencephalopathy | |
| HP:0000369 | Low-set ears | |
| HP:0031165 | Multifocal seizures | |
| HP:0001998 | Neonatal hypoglycemia | |
| HP:0000639 | Nystagmus | |
| HP:0002421 | Poor head control | |
| HP:0005656 | Positional foot deformity | |
| HP:0000510 | Rod-cone dystrophy | |
| HP:0002510 | Spastic tetraplegia | |
| HP:0000219 | Thin upper lip vermilion | |
| HP:0001873 | Thrombocytopenia | |
| HP:0001337 | Tremor | |
| HP:0000431 | Wide nasal bridge | |
| HP:0012704 | Widened subarachnoid space | |
Run the differential on the 4 obligate / very frequent terms
Annotation source: 29783990[PMID]_28236339[PMID]_28650581[PMID]_28905505[PMID]
Sources for this card
- Orphanet page: orpha.net/en/disease/detail/572798
- This record as JSON: /data/d/572798.json