Methylcobalamin deficiency type cblDv1

General Information (adopted from Orphanet):

Synonyms, Signs: METHYLMALONIC ACIDEMIA, cblH TYPE, FORMERLY
METHYLMALONIC ACIDURIA, cblD TYPE, VARIANT 2, INCLUDED
METHYLMALONIC ACIDURIA, cblH TYPE, FORMERLY
Functional methionine synthase deficiency type cblDv1
METHYLMALONIC ACIDEMIA AND HOMOCYSTINURIA, cblD TYPE HOMOCYSTINURIA, cblD TYPE, VARIANT 1, INCLUDED
Number of Symptoms 26
OrphanetNr: 308380
OMIM Id: 277410
ICD-10: E72.1
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive inheritance
[Omim]
Age of onset: Infantile onset
[Omim]

Disease classification (adopted from Orphanet):

Parent Diseases: Homocystinuria without methylmalonic aciduria
 -Rare genetic disease
 -Rare hematologic disease
 -Rare neurologic disease

Symptom Information: Sort by abundance 

1
 (HPO:0012120) Methylmalonic aciduria 20 / 7739
2
 (HPO:0002156) Homocystinuria 12 / 7739
3
 (HPO:0000639) Nystagmus 555 / 7739
4
 (HPO:0001249) Intellectual disability 1089 / 7739
5
 (HPO:0001250) Seizures 1245 / 7739
6
 (HPO:0002497) Spastic ataxia 13 / 7739
7
 (HPO:0001332) Dystonia 197 / 7739
8
 (HPO:0001263) Global developmental delay 853 / 7739
9
 (HPO:0001254) Lethargy 104 / 7739
10
 (HPO:0001889) Megaloblastic anemia 28 / 7739
11
 (HPO:0005518) Erythrocyte macrocytosis 13 / 7739
12
 (HPO:0003658) Hypomethioninemia 6 / 7739
13
 (HPO:0003145) Decreased adenosylcobalamin 10 / 7739
14
 (HPO:0002912) Methylmalonic acidemia 14 / 7739
15
 (HPO:0003524) Decreased methionine synthase activity 9 / 7739
16
 (HPO:0003210) Decreased methylmalonyl-CoA mutase activity 7 / 7739
17
 (HPO:0002160) Hyperhomocystinemia 10 / 7739
18
 (HPO:0003223) Decreased methylcobalamin 11 / 7739
19
 (HPO:0008947) Infantile muscular hypotonia 482 / 7739
20
 (HPO:0010547) Muscle flaccidity 466 / 7739
21
 (HPO:0001252) Muscular hypotonia 990 / 7739
22
 (HPO:0001324) Muscle weakness 859 / 7739
23
 (HPO:0003593) Infantile onset 249 / 7739
24
 (HPO:0002120) Cerebral cortical atrophy 187 / 7739
25
 (OMIM) Normal or mildly reduced serum cobalamin 3 / 7739
26
 (HPO:0000007) Autosomal recessive inheritance 2538 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Combined methylmalonic aciduria (MMA) and homocystinuria is a genetically heterogeneous disorder of cobalamin (cbl; vitamin B12) metabolism. The defect causes decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl), which results in decreased activity of the respective ...
Clinical Description OMIM - CblD Combined Homocystinuria and Methylmalonic Aciduria

Goodman et al. (1970) reported 2 brothers, from a consanguineous family, with combined homocystinuria and methylmalonic aciduria. The older sib presented with developmental delay and neurologic abnormalities at age ...
Genotype-Phenotype Correlations OMIM Stucki et al. (2012) studied the effect of various MMADHC constructs on protein function in cell lines. For example, mutant alleles associated with the cblD-homocystinuria (HC) phenotype were unable to rescue MeCbl synthesis, whereas mutant alleles associated with ...
Molecular genetics OMIM Coelho et al. (2008) identified biallelic mutations in the C2ORF25 gene in cblD patients with homocystinuria (611934.0001-611934.0003), methylmalonic aciduria (611934.0004-611934.0006), and combined homocystinuria and methylmalonic aciduria (611934.0007-611934.0009). Five of the patients had previously been reported by Goodman et ...