ORPHA:765
Pyruvate dehydrogenase deficiency
Synonyms: PDH · PDHC · Pyruvate dehydrogenase complex deficiency
- Type
- Disease
- Group
- Disorder
- Inheritance
- Autosomal recessive, Not applicable, X-linked dominant
- Age of onset
- Childhood, Infancy, Neonatal
- Status
- active
Pyruvate dehydrogenase deficiency (PDHD) is a rare neurometabolic disorder characterized by a wide range of clinical signs with metabolic and neurological components of varying severity. Manifestations range from often fatal, severe, neonatal lactic acidosis to later-onset neurological disorders. Six subtypes related to the affected subunit of the PDH complex have been recognized with significant clinical overlap: PDHD due to E1-alpha, E1-beta, E2 and E3 deficiency, PDHD due to E3-binding protein deficiency, and PDH phosphatase deficiency.
1
Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | Pyruvate dehydrogenase deficiency | PDH · PDHC · Pyruvate dehydrogenase complex deficiency |
| fr | Déficit en pyruvate déshydrogénase | PDH · PDHC · Déficit en complexe pyruvate déshydrogénase |
| de | Pyruvat-Dehydrogenase-Mangel | PDHc · Pyruvat-Dehydrogenase-Komplex-Mangel |
| es | Deficiencia de piruvato deshidrogenasa | Deficiencia del complejo piruvato deshidrogenasa · PDH · PDHC |
| it | Deficit della piruvato deidrogenasi | Deficit del complesso della piruvato deidrogenasi · PDH · PDHC |
| nl | Pyruvaatdehydrogenasedeficiëntie | Deficiëntie van het pyruvaatdehydrogenasecomplex · PDH · PDHC |
| pt | Deficiência de piruvato desidrogenase | |
| pl | Niedobór dehydrogenazy pirogronianowej | Niedobór kompleksu dehydrogenazy pirogronianowej · PDH · PDHC |
| cs | Deficit pyruvát dehydrogenázy | PDH · PDHC · Deficit komplexu pyruvát dehydrogenázy |
| uk | Дефіцит піруватдегідрогенази | PDH · PDHC · Дефіцит піруватдегідрогеназного комплексу |
| zh | 丙酮酸脱氢酶缺乏症 | 丙酮酸脱氢酶复合物缺乏症 |
| tr | Piruvat dehidrojenaz eksikliği | PDH · PDHC · Piruvat dehidrojenaz kompleks eksikliği |
Definition in:
2
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 245348 | BTNT | validated | |
| OMIM | 245349 | BTNT | validated | |
| OMIM | 246900 | BTNT | validated | |
| OMIM | 312170 | BTNT | validated | |
| OMIM | 608782 | BTNT | validated | |
| OMIM | 614111 | BTNT | validated | |
| ICD-10 | E74.4 | NTBT | inclusion | validated |
| ICD-11 | 5C53.02 | E | specific | validated |
| MONDO | 0019169 | E | validated | |
| MeSH | D015325 | E | validated | |
| UMLS | C0034345 | E | validated | |
| GARD | 7513 | E | validated | |
| MedDRA | 10084109 | E | validated |
E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.
3
Classification
Preferential parent (Orphanet linearisation):
Parents in the classifications (5):
- ORPHA:225700Mitochondrial disease with epilepsy
rare genetic diseases; rare neurological diseases - ORPHA:225703Mitochondrial disease with peripheral neuropathy
rare genetic diseases; rare neurological diseases - ORPHA:68385Neurometabolic disease
rare genetic diseases; rare neurological diseases - ORPHA:254746Pyruvate metabolism disorder
rare inborn errors of metabolism; rare genetic diseases - ORPHA:611314Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome
rare genetic diseases; rare neurological diseases
Children (6):
- ORPHA:79243Pyruvate dehydrogenase E1-alpha deficiency
- ORPHA:255138Pyruvate dehydrogenase E1-beta deficiency
- ORPHA:79244Pyruvate dehydrogenase E2 deficiency
- ORPHA:2394Pyruvate dehydrogenase E3 deficiency
- ORPHA:255182Pyruvate dehydrogenase E3-binding protein deficiency
- ORPHA:79246Pyruvate dehydrogenase phosphatase deficiency
4
Genes
0 direct · 7 via subtypesOrphanet records no gene directly on this code.
Recorded by Orphanet on subtypes of this disorder:
| Gene | Subtype | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|---|
| DLAT | ORPHA:79244Pyruvate dehydrogenase E2 deficiency | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:2896 | ENSG00000150768 | 608770 | 11q23.1 | dihydrolipoamide S-acetyltransferase | 16049940[PMID] |
| DLD | ORPHA:2394Pyruvate dehydrogenase E3 deficiency | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:2898 | ENSG00000091140 | 238331 | 7q31.1 | dihydrolipoamide dehydrogenase | 24777537[PMID] |
| PDP1 | ORPHA:79246Pyruvate dehydrogenase phosphatase deficiency | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:9279 | ENSG00000164951 | 605993 | 8q22.1 | pyruvate dehydrogenase phosphatase catalytic subunit 1 | 15855260[PMID] |
| LONP1 | ORPHA:79243Pyruvate dehydrogenase E1-alpha deficiency | Disease-causing germline mutation(s) in | Assessed | HGNC:9479 | ENSG00000196365 | 605490 | 19p13.2 | lon peptidase 1, mitochondrial | 30304514[PMID] |
| PDHA1 | ORPHA:79243Pyruvate dehydrogenase E1-alpha deficiency | Disease-causing germline mutation(s) in | Assessed | HGNC:8806 | ENSG00000131828 | 300502 | Xp22.12 | pyruvate dehydrogenase E1 subunit alpha 1 | 10679936[PMID]_15384102[PMID]_20002461[PMID] |
| PDHB | ORPHA:255138Pyruvate dehydrogenase E1-beta deficiency | Disease-causing germline mutation(s) in | Assessed | HGNC:8808 | ENSG00000168291 | 179060 | 3p14.3 | pyruvate dehydrogenase E1 subunit beta | 15138885[PMID] |
| PDHX | ORPHA:255182Pyruvate dehydrogenase E3-binding protein deficiency | Disease-causing germline mutation(s) in | Assessed | HGNC:21350 | ENSG00000110435 | 608769 | 11p13 | pyruvate dehydrogenase complex component X | 9399911[PMID] |
5
Prevalence and incidence
2 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Point prevalence | Unknown | — | Worldwide | Class only | Not yet validated | ORPHANET |
| Point prevalence | <1 / 1 000 000 | — | Europe | Class only | Validated | European Medicines Agency 2015[OTHER] |
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
35 annotations · validated 2016-06-01| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Very frequent (99-80%) | ||
| HP:0001999 | Abnormal facial shape | |
| HP:0008872 | Feeding difficulties in infancy | |
| HP:0001510 | Growth delay | |
| HP:0001252 | Hypotonia | |
| HP:0001254 | Lethargy | |
| Frequent (79-30%) | ||
| HP:0007256 | Abnormal pyramidal sign | |
| HP:0000496 | Abnormality of eye movement | |
| HP:0007370 | Aplasia/Hypoplasia of the corpus callosum | |
| HP:0001251 | Ataxia | |
| HP:0001266 | Choreoathetosis | |
| HP:0001260 | Dysarthria | |
| HP:0001288 | Gait disturbance | |
| HP:0001263 | Global developmental delay | |
| HP:0001511 | Intrauterine growth retardation | |
| HP:0000252 | Microcephaly | |
| HP:0100453 | Osteolytic defects of the middle phalanx of the 4th toe | |
| HP:0001250 | Seizure | |
| HP:0001257 | Spasticity | |
| HP:0002789 | Tachypnea | |
| HP:0001337 | Tremor | |
| Occasional (29-5%) | ||
| HP:0100021 | Cerebral palsy | |
| HP:0002094 | Dyspnea | |
| HP:0001332 | Dystonia | |
| HP:0000286 | Epicanthus | |
| HP:0002007 | Frontal bossing | |
| HP:0000218 | High palate | |
| HP:0000316 | Hypertelorism | |
| HP:0000343 | Long philtrum | |
| HP:0001012 | Multiple lipomas | |
| HP:0000275 | Narrow face | |
| HP:0000767 | Pectus excavatum | |
| HP:0000243 | Trigonocephaly | |
| HP:0000582 | Upslanted palpebral fissure | |
| HP:0002119 | Ventriculomegaly | |
| HP:0000431 | Wide nasal bridge | |
Run the differential on the 5 obligate / very frequent terms
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Sources for this card
- Orphanet page: orpha.net/en/disease/detail/765
- This record as JSON: /data/d/765.json