Methylmalonic acidemia with homocystinuria, type cblD

General Information (adopted from Orphanet):

Synonyms, Signs: METHYLMALONIC ACIDEMIA, cblH TYPE, FORMERLY
METHYLMALONIC ACIDURIA, cblD TYPE, VARIANT 2, INCLUDED
METHYLMALONIC ACIDURIA, cblH TYPE, FORMERLY
Combined defect in adenosylcobalamin and methylcobalamin synthesis, type cblD
Methylmalonic aciduria with homocystinuria, type cblD
METHYLMALONIC ACIDEMIA AND HOMOCYSTINURIA, cblD TYPE HOMOCYSTINURIA, cblD TYPE, VARIANT 1, INCLUDED
Number of Symptoms 32
OrphanetNr: 79283
OMIM Id: 277410
ICD-10: E72.1
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 17 cases [Orphanet]
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: All ages
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Methylmalonic acidemia with homocystinuria
 -Rare genetic disease
 -Rare hematologic disease

Symptom Information: Sort by abundance 

1
 (HPO:0002039) Anorexia Very frequent [Orphanet] 62 / 7739
2
 (HPO:0000639) Nystagmus 555 / 7739
3
 (HPO:0003210) Decreased methylmalonyl-CoA mutase activity 7 / 7739
4
 (HPO:0004325) Decreased body weight Very frequent [Orphanet] 492 / 7739
5
 (HPO:0003524) Decreased methionine synthase activity 9 / 7739
6
 (HPO:0003658) Hypomethioninemia 6 / 7739
7
 (HPO:0002156) Homocystinuria 12 / 7739
8
 (HPO:0002160) Hyperhomocystinemia 10 / 7739
9
 (HPO:0012120) Methylmalonic aciduria 20 / 7739
10
 (HPO:0002912) Methylmalonic acidemia 14 / 7739
11
 (HPO:0001889) Megaloblastic anemia Very frequent [Orphanet] 28 / 7739
12
 (HPO:0005518) Erythrocyte macrocytosis 13 / 7739
13
 (HPO:0001252) Muscular hypotonia 990 / 7739
14
 (HPO:0008947) Infantile muscular hypotonia 482 / 7739
15
 (HPO:0010547) Muscle flaccidity 466 / 7739
16
 (HPO:0001324) Muscle weakness Very frequent [Orphanet] 859 / 7739
17
 (HPO:0002497) Spastic ataxia 13 / 7739
18
 (HPO:0001332) Dystonia 197 / 7739
19
 (HPO:0000708) Behavioral abnormality Very frequent [Orphanet] 212 / 7739
20
 (HPO:0001263) Global developmental delay 853 / 7739
21
 (HPO:0001249) Intellectual disability 1089 / 7739
22
 (HPO:0001254) Lethargy 104 / 7739
23
 (HPO:0004372) Reduced consciousness/confusion Very frequent [Orphanet] 73 / 7739
24
 (HPO:0100022) Abnormality of movement Very frequent [Orphanet] 129 / 7739
25
 (HPO:0001288) Gait disturbance Very frequent [Orphanet] 318 / 7739
26
 (HPO:0001250) Seizures Very frequent [Orphanet] 1245 / 7739
27
 (HPO:0000980) Pallor Very frequent [Orphanet] 52 / 7739
28
 (HPO:0003145) Decreased adenosylcobalamin 10 / 7739
29
 (HPO:0003223) Decreased methylcobalamin 11 / 7739
30
 (HPO:0002120) Cerebral cortical atrophy 187 / 7739
31
 (HPO:0012758) Neurodevelopmental delay Very frequent [Orphanet] 949 / 7739
32
 (OMIM) Normal or mildly reduced serum cobalamin 3 / 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 ...