ORPHA:26
Methylmalonic acidemia with homocystinuria
Synonyms: Combined defect in adenosylcobalamin and methylcobalamin synthesis · Methylmalonic aciduria with homocystinuria
- Type
- Disease
- Group
- Disorder
- Inheritance
- Autosomal recessive, X-linked recessive
- Age of onset
- All ages
- Status
- active
A rare inborn error of vitamin B12 (cobalamin) metabolism characterized by megaloblastic anemia, lethargy, failure to thrive, developmental delay, intellectual deficit and seizures. There are four complementation classes of cobalamin defects (cblC, cblD, cblF and cblJ) that are responsible for methylmalonic acidemia - homocystinuria (methylmalonic acidemia - homocystinuria cblC, cblD cblF and cblJ).
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Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | Methylmalonic acidemia with homocystinuria | Combined defect in adenosylcobalamin and methylcobalamin synthesis · Methylmalonic aciduria with homocystinuria |
| fr | Acidémie méthylmalonique avec homocystinurie | Acidurie méthylmalonique avec homocystinurie · Déficit combiné de synthèse de l'adénosylcobalamine et de la méthylcobalamine |
| de | Methylmalonazidämie mit Homocystinurie | Kombinierter Defekt der Adenosylcobalamin und Methylcobalamin-Synthese · Methylmalonacidurie - Homocystinurie |
| es | Acidemia metilmalónica con homocistinuria | Aciduria metilmalónica con homocistinuria · Defecto combinado en la síntesis de adenosilcobalamina y metilcobalamina |
| it | Acidemia metilmalonica con omocistinuria | Aciduria metilmalonica con omocistinuria · Difetto combinato della sintesi dell'adenosilcobalamina e della metilcobalamina · Metilmalonicaciduria - omocistinuria |
| nl | Methylmalonacidemie met homocystinurie | Gecombineerd defect in adenosylcobalamine- en methylcobalaminesynthese · Methylmalonacidurie met homocystinurie · Methylmalonzuuracidemie met homocystinurie · Methylmalonzuuracidurie met homocystinurie |
| pt | Acidemia metilmalónica com homocistinúria | Acidemia metilmalónica-homocistinúria |
| pl | Kwasica metylomalonowa z homocystynurią | Acyduria metylomalonowa z homocystynurią · Łączony defekt w syntezie adenozylokobalaminy i metylkobalaminy |
| cs | Methylmalonová acidémie s homocystinurií | Kombinovaná porucha syntézy adenosylkobalaminu a methylkobalaminu · Methylmalonová acidurie s homocysteinurií |
| uk | Метилмалонова ацидемія з гомоцистинурією | Поєднаний дефект синтезу аденозилкобаламіну та метилкобаламіну · Метилмалоновий ацидоз з гомоцистинурією |
| zh | 甲基丙二酸血症伴高胱氨酸尿症 | 腺苷钴胺素和甲基钴胺素合成联合缺陷 |
| tr | Homosistinüri ile birlikte metilmalonik asidemi | Homosistinüri ile seyreden metilmalonik asidüri · Adenozilkobalamin ve metilkobalamin sentezinde kombine defekt |
Definition in:
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Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 277380 | BTNT | validated | |
| OMIM | 277400 | BTNT | validated | |
| OMIM | 277410 | BTNT | validated | |
| OMIM | 614857 | BTNT | validated | |
| ICD-10 | E71.1 | NTBT | attributed | validated |
| ICD-11 | 5C50.E0 | NTBT | index | validated |
| MONDO | 0016826 | E | validated | |
| MeSH | C537359 | E | validated | |
| UMLS | C5848324 | E | validated | |
| GARD | 3579 | 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 (5):
- ORPHA:79163Classic organic aciduria
rare inborn errors of metabolism; rare genetic diseases - ORPHA:98396Constitutional megaloblastic anemia due to vitamin B12 metabolism disorder
rare genetic diseases; rare hematological diseases - ORPHA:79171Disorder of cobalamin metabolism and transport
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
Children (5):
- ORPHA:79284Methylmalonic acidemia with homocystinuria type cblF
- ORPHA:79282Methylmalonic acidemia with homocystinuria, type cblC
- ORPHA:79283Methylmalonic acidemia with homocystinuria, type cblD
- ORPHA:369955Methylmalonic acidemia with homocystinuria, type cblJ
- ORPHA:369962Methylmalonic acidemia with homocystinuria, type cblX
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Genes
0 direct · 5 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 |
|---|---|---|---|---|---|---|---|---|---|
| ABCD4 | ORPHA:369955Methylmalonic acidemia with homocystinuria, type cblJ | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:68 | ENSG00000119688 | 603214 | 14q24.3 | ATP binding cassette subfamily D member 4 | 22922874[PMID] |
| HCFC1 | ORPHA:369962Methylmalonic acidemia with homocystinuria, type cblX | Disease-causing germline mutation(s) in | Assessed | HGNC:4839 | ENSG00000172534 | 300019 | Xq28 | host cell factor C1 | 24011988[PMID] |
| LMBRD1 | ORPHA:79284Methylmalonic acidemia with homocystinuria type cblF | Disease-causing germline mutation(s) in | Assessed | HGNC:23038 | ENSG00000168216 | 612625 | 6q13 | LMBR1 domain containing 1 | 20301503[PMID] |
| MMACHC | ORPHA:79282Methylmalonic acidemia with homocystinuria, type cblC | Disease-causing germline mutation(s) in | Assessed | HGNC:24525 | ENSG00000132763 | 609831 | 1p34.1 | metabolism of cobalamin associated C | 16311595[PMID]_21497120[PMID] |
| MMADHC | ORPHA:79283Methylmalonic acidemia with homocystinuria, type cblD | Disease-causing germline mutation(s) in | Assessed | HGNC:25221 | ENSG00000168288 | 611935 | 2q23.2 | metabolism of cobalamin associated D | 20301409[PMID]_20301503[PMID] |
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Prevalence and incidence
2 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Cases/families | 500 cases | Worldwide | Case(s) | Validated | 16714133[PMID]_[EXPERT] | |
| Point prevalence | Unknown | — | Worldwide | Class only | Validated | ORPHANET |
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
18 annotations · validated 2016-06-01| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Very frequent (99-80%) | ||
| HP:0000646 | Amblyopia | |
| HP:0001508 | Failure to thrive | |
| HP:0012378 | Fatigue | |
| HP:0011968 | Feeding difficulties | |
| HP:0001263 | Global developmental delay | |
| HP:0001252 | Hypotonia | |
| HP:0001249 | Intellectual disability | |
| HP:0001254 | Lethargy | |
| HP:0001980 | Megaloblastic bone marrow | |
| HP:0000252 | Microcephaly | |
| HP:0000488 | Retinopathy | |
| HP:0001250 | Seizure | |
| Frequent (79-30%) | ||
| HP:0030680 | Abnormal cardiovascular system morphology | |
| HP:0100022 | Abnormality of movement | |
| HP:0000708 | Atypical behavior | |
| HP:0001288 | Gait disturbance | |
| HP:0000238 | Hydrocephalus | |
| Occasional (29-5%) | ||
| HP:0000988 | Skin rash | |
Run the differential on the 12 obligate / very frequent terms
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Sources for this card
- Orphanet page: orpha.net/en/disease/detail/26
- This record as JSON: /data/d/26.json