ORPHA:622
Homocystinuria without methylmalonic aciduria
Synonyms: Functional methionine synthase deficiency · Methylcobalamin deficiency
- Type
- Disease
- Group
- Disorder
- Inheritance
- Autosomal recessive
- Age of onset
- All ages
- Status
- active
Homocystinuria without methylmalonic aciduria is an inborn error of vitamin B12 (cobalamin) metabolism characterized by megaloblastic anemia, encephalopathy and, sometimes, developmental delay, and associated with homocystinuria and hyperhomocysteinemia. There are three types of homocystinuria without methylmalonic aciduria; <i>cblE, cblG</i> and <i>cblD-</i>variant 1 (<i>cblD</i>v1).
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Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | Homocystinuria without methylmalonic aciduria | Functional methionine synthase deficiency · Methylcobalamin deficiency |
| fr | Homocystinurie sans acidurie méthylmalonique | Déficit en méthylcobalamine · Déficit fonctionnel en méthionine synthase |
| de | Homocystinurie ohne Methylmalonazidurie | Methioninsynthase-Mangel, funktioneller · Methylcobalamin-Mangel |
| es | Homocistinuria sin aciduria metilmalónica | Deficiencia de metilcobalamina · Deficiencia funcional de metionina sintasa |
| it | Omocistinuria senza aciduria metilmalonica | Deficit di metilcobalamina · Deficit funzionale di metionina sintasi |
| nl | Homocystinurie zonder methylmalonacidurie | Deficiëntie van methylcobalamine · Functionele deficiëntie van methioninesynthase · Homocystinurie zonder methylmalonzuuracidurie |
| pt | Homocistinúria sem acidúria metilmalónica | Deficiência de metilcobalamina · Deficiência funcional de metionina sintetase |
| pl | Homocystinuria bez acydurii metylomalonowej | Funkcjonalny Niedobór syntazy metioniny · Niedobór metylokobalaminy |
| cs | Homocystinurie bez methylmalonové acidurie | Deficit methylkobalaminu · Funkční deficit methioninsyntázy |
| uk | Гомоцистинурія без метилмалонової ацидурії | Функціональна недостатність метіонінсинтетази · Дефіцит метилкобаламіну |
| zh | 同型半胱氨酸血症不伴甲基丙二酸尿症 | 功能性甲硫氨酸合成缺乏症 |
| tr | Metilmalonik asidüri ile seyretmeyen homosistinüri | Metilkobalamin eksikliği · Fonksiyonel metiyonin sentaz eksikliği |
Definition in:
2
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 236270 | BTNT | validated | |
| OMIM | 250940 | BTNT | validated | |
| OMIM | 277410 | BTNT | validated | |
| ICD-10 | E72.1 | NTBT | attributed | validated |
| ICD-11 | 5C50.B | NTBT | index | validated |
| MONDO | 0018964 | E | validated | |
| UMLS | C4303479 | 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 (4):
- 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:79173Disorder of methionine cycle and sulfur amino acid metabolism
rare inborn errors of metabolism; rare genetic diseases - ORPHA:68385Neurometabolic disease
rare genetic diseases; rare neurological diseases
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Genes
0 direct · 3 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 |
|---|---|---|---|---|---|---|---|---|---|
| MMADHC | ORPHA:308380Methylcobalamin deficiency type cblDv1 | Disease-causing germline mutation(s) in | Assessed | HGNC:25221 | ENSG00000168288 | 611935 | 2q23.2 | metabolism of cobalamin associated D | 18385497[PMID] |
| MTR | ORPHA:2170Methylcobalamin deficiency type cblG | Disease-causing germline mutation(s) in | Assessed | HGNC:7468 | ENSG00000116984 | 156570 | 1q43 | 5-methyltetrahydrofolate-homocysteine methyltransferase | 20301503[PMID] |
| MTRR | ORPHA:2169Methylcobalamin deficiency type cblE | Disease-causing germline mutation(s) in | Assessed | HGNC:7473 | ENSG00000124275 | 602568 | 5p15.31 | 5-methyltetrahydrofolate-homocysteine methyltransferase reductase | 20301503[PMID] |
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Prevalence and incidence
2 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Cases/families | 73 cases | Worldwide | Case(s) | Validated | [EXPERT] | |
| Point prevalence | <1 / 1 000 000 | — | 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
31 annotations · validated 2026-02-12| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Very frequent (99-80%) | ||
| HP:0002156 | Homocystinuria | |
| Frequent (79-30%) | ||
| HP:0002120 | Cerebral cortical atrophy | |
| HP:0002329 | Drowsiness | |
| HP:0001298 | Encephalopathy | |
| HP:0001508 | Failure to thrive | |
| HP:0011968 | Feeding difficulties | |
| HP:0001263 | Global developmental delay | |
| HP:0002160 | Hyperhomocystinemia | |
| HP:0001252 | Hypotonia | |
| HP:0001249 | Intellectual disability | |
| HP:0001972 | Macrocytic anemia | |
| HP:0000639 | Nystagmus | |
| HP:0000709 | Psychosis | |
| HP:0000488 | Retinopathy | |
| HP:0001250 | Seizure | |
| HP:0000486 | Strabismus | |
| Occasional (29-5%) | ||
| HP:0001251 | Ataxia | |
| HP:0000708 | Atypical behavior | |
| HP:0012444 | Brain atrophy | |
| HP:0000726 | Dementia | |
| HP:0001510 | Growth delay | |
| HP:0003658 | Hypomethioninemia | |
| HP:0001254 | Lethargy | |
| HP:0004372 | Reduced consciousness | |
| HP:0007663 | Reduced visual acuity | |
| HP:0000505 | Visual impairment | |
| HP:0002013 | Vomiting | |
| Very rare (<4-1%) | ||
| HP:0005575 | Hemolytic-uremic syndrome | |
| HP:0012469 | Infantile spasms | |
| HP:0000648 | Optic atrophy | |
| Excluded (0%) | ||
| HP:0002912 | Methylmalonic acidemia | |
Run the differential on the 1 obligate / very frequent terms
Annotation source: 25526710[PMID]_34625984[PMID]_20301503[PMID]
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Sources for this card
- Orphanet page: orpha.net/en/disease/detail/622
- This record as JSON: /data/d/622.json