Fumaric aciduria
Synonyms: Fumarase deficiency
- Type
- Disease
- Group
- Disorder
- Inheritance
- Autosomal recessive
- Age of onset
- Infancy, Neonatal
- Status
- active
Fumaric aciduria (FA), an autosomal recessive metabolic disorder, is most often characterized by early onset but non-specific clinical signs: hypotonia, severe psychomotor impairment, convulsions, respiratory distress, feeding difficulties and frequent cerebral malformations, along with a distinctive facies. Some patients present with only moderate intellectual impairment.
Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | Fumaric aciduria | Fumarase deficiency |
| fr | Acidurie fumarique | Déficit en fumarase |
| de | Fumarazidurie | Fumarase-Mangel |
| es | Aciduria fumárica | Deficiencia de fumarasa |
| it | Aciduria fumarica | Deficit di fumarasi |
| nl | Fumarasedeficiëntie | Fumaarzuuracidurie |
| pt | Acidúria fumárica | Deficiência de fumarase |
| pl | Acyduria fumarowa | Niedobór fumarazy |
| cs | Fumarová acidurie | Deficit fumarázy |
| uk | Фумарова ацидурія | Дефіцит фумарази |
| zh | 富马酸尿症 | 延胡索酸酶缺乏症 |
| tr | Fumarik asidüri | Fumaraz eksikliği |
Definition in:
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 606812 | E | validated | |
| ICD-10 | E88.8 | NTBT | attributed | validated |
| ICD-11 | 5C53.1 | NTBT | index | validated |
| MONDO | 0011730 | E | validated | |
| MeSH | C538191 | E | validated | |
| UMLS | C0342770 | E | validated | |
| GARD | 6476 | E | validated | |
| MedDRA | 10088204 | 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 (4):
- 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:254749Tricarboxylic acid cycle disorder
rare inborn errors of metabolism; rare genetic diseases
No children.
Genes
1 direct| Gene | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|
| FH | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:3700 | ENSG00000091483 | 136850 | 1q43 | fumarate hydratase | 20301679[PMID] |
Prevalence and incidence
2 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Cases/families | 40 cases | Worldwide | Case(s) | Validated | 22069215[PMID] | |
| Point prevalence | <1 / 1 000 000 | — | Worldwide | Class only | Validated | ORPHANET_22069215[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
44 annotations · validated 2025-06-05| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Very frequent (99-80%) | ||
| HP:0003536 | Decreased fumarate hydratase activity | |
| Frequent (79-30%) | ||
| HP:0002059 | Cerebral atrophy | |
| HP:0005280 | Depressed nasal bridge | |
| HP:0001298 | Encephalopathy | |
| HP:0001531 | Failure to thrive in infancy | |
| HP:0008872 | Feeding difficulties in infancy | |
| HP:0002007 | Frontal bossing | |
| HP:0001263 | Global developmental delay | |
| HP:0000316 | Hypertelorism | |
| HP:0001252 | Hypotonia | |
| HP:0001254 | Lethargy | |
| HP:0001561 | Polyhydramnios | |
| HP:0001622 | Premature birth | |
| HP:0001250 | Seizure | |
| HP:0002119 | Ventriculomegaly | |
| Occasional (29-5%) | ||
| HP:0002500 | Abnormal cerebral white matter morphology | |
| HP:0001273 | Abnormal corpus callosum morphology | |
| HP:0000463 | Anteverted nares | |
| HP:0025646 | Bilateral polymicrogyria | |
| HP:0006808 | Cerebral hypomyelination | |
| HP:0100704 | Cerebral visual impairment | |
| HP:0003191 | Cleft ala nasi | |
| HP:0001259 | Coma | |
| HP:0001875 | Decreased total neutrophil count | |
| HP:0012448 | Delayed myelination | |
| HP:0001332 | Dystonia | |
| HP:0034648 | Elevated urine fumaric acid level | |
| HP:0002240 | Hepatomegaly | |
| HP:0002521 | Hypsarrhythmia | |
| HP:0012402 | Increased urine alpha-ketoglutarate concentration | |
| HP:0012469 | Infantile spasms | |
| HP:0001511 | Intrauterine growth retardation | |
| HP:0000252 | Microcephaly | |
| HP:0001562 | Oligohydramnios | |
| HP:0000648 | Optic atrophy | |
| HP:0001901 | Polycythemia | |
| HP:0002421 | Poor head control | |
| HP:0000817 | Reduced eye contact | |
| HP:0010804 | Tented upper lip vermilion | |
| HP:0002013 | Vomiting | |
| Very rare (<4-1%) | ||
| HP:0001987 | Hyperammonemia | |
| HP:0001943 | Hypoglycemia | |
| HP:0003128 | Lactic acidosis | |
| HP:0001942 | Metabolic acidosis | |
Run the differential on the 1 obligate / very frequent terms
Annotation source: 20301679[PMID]_33052056[PMID]
Sources for this card
- Orphanet page: orpha.net/en/disease/detail/24
- This record as JSON: /data/d/24.json