Methylmalonic acidemia with homocystinuria, type cblC

General Information (adopted from Orphanet):

Synonyms, Signs: METHYLMALONIC ACIDURIA AND HOMOCYSTINURIA, VITAMIN B12-RESPONSIVE
Combined defect in adenosylcobalamin and methylcobalamin synthesis, type cblC
VITAMIN B12 METABOLIC DEFECT WITH COMBINED DEFICIENCY OF METHYLMALONYL-CoA MUTASE AND HOMOCYSTEINE:METHYLTETRAHYDROFOLATE METHYLTRANSFERASE
Methylmalonic aciduria with homocystinuria, type cblC
METHYLMALONIC ACIDEMIA AND HOMOCYSTINURIA, cblC TYPE
Number of Symptoms 68
OrphanetNr: 79282
OMIM Id: 277400
ICD-10: E72.1
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 500 cases [Orphanet]
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: All ages
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Metabolic disease with pigmentary retinitis
 -Rare eye disease
 -Rare genetic disease
Methylmalonic acidemia with homocystinuria
 -Rare genetic disease
 -Rare hematologic disease
Rare hereditary metabolic disease with peripheral neuropathy
 -Rare genetic disease
 -Rare neurologic disease

Symptom Information: Sort by abundance 

1
 (HPO:0002039) Anorexia Very frequent [Orphanet] 62 / 7739
2
 (HPO:0011968) Feeding difficulties 240 / 7739
3
 (HPO:0008872) Feeding difficulties in infancy 153 / 7739
4
 (MedDRA:10043645) Thrombotic microangiopathy 11 / 7739
5
 (HPO:0000580) Pigmentary retinopathy 49 / 7739
6
 (HPO:0000488) Retinopathy Very frequent [Orphanet] 75 / 7739
7
 (HPO:0000639) Nystagmus 555 / 7739
8
 (HPO:0000505) Visual impairment 297 / 7739
9
 (HPO:0007663) Reduced visual acuity 100 / 7739
10
 (HPO:0001907) Thromboembolism 15 / 7739
11
 (HPO:0003210) Decreased methylmalonyl-CoA mutase activity 7 / 7739
12
 (HPO:0001942) Metabolic acidosis 81 / 7739
13
 (HPO:0004325) Decreased body weight Very frequent [Orphanet] 492 / 7739
14
 (HPO:0001508) Failure to thrive 454 / 7739
15
 (HPO:0003524) Decreased methionine synthase activity 9 / 7739
16
 (HPO:0003658) Hypomethioninemia 6 / 7739
17
 (HPO:0003286) Cystathioninemia 3 / 7739
18
 (HPO:0003153) Cystathioninuria 5 / 7739
19
 (HPO:0002156) Homocystinuria 12 / 7739
20
 (HPO:0002160) Hyperhomocystinemia 10 / 7739
21
 (HPO:0012120) Methylmalonic aciduria 20 / 7739
22
 (HPO:0002912) Methylmalonic acidemia 14 / 7739
23
 (HPO:0001903) Anemia 289 / 7739
24
 (HPO:0001889) Megaloblastic anemia Very frequent [Orphanet] 28 / 7739
25
 (HPO:0001875) Neutropenia 83 / 7739
26
 (HPO:0001252) Muscular hypotonia 990 / 7739
27
 (HPO:0008947) Infantile muscular hypotonia 482 / 7739
28
 (HPO:0010547) Muscle flaccidity 466 / 7739
29
 (HPO:0001324) Muscle weakness Very frequent [Orphanet] 859 / 7739
30
 (HPO:0002071) Abnormality of extrapyramidal motor function 76 / 7739
31
 (HPO:0001289) Confusion 36 / 7739
32
 (MedDRA:10012221) Deliria (incl confusion) 2 / 7739
33
 (MedDRA:10012219) Deliria 2 / 7739
34
 (HPO:0000726) Dementia 131 / 7739
35
 (HPO:0001263) Global developmental delay 853 / 7739
36
 (HPO:0001249) Intellectual disability 1089 / 7739
37
 (HPO:0000738) Hallucinations 60 / 7739
38
 (HPO:0001254) Lethargy 104 / 7739
39
 (HPO:0004372) Reduced consciousness/confusion Very frequent [Orphanet] 73 / 7739
40
 (HPO:0001337) Tremor 200 / 7739
41
 (HPO:0001250) Seizures Very frequent [Orphanet] 1245 / 7739
42
 (HPO:0000348) High forehead 157 / 7739
43
 (HPO:0000252) Microcephaly Very frequent [Orphanet] 832 / 7739
44
 (HPO:0000276) Long face 109 / 7739
45
 (HPO:0000319) Smooth philtrum 72 / 7739
46
 (HPO:0000400) Macrotia 108 / 7739
47
 (HPO:0000369) Low-set ears 372 / 7739
48
 (HPO:0000980) Pallor Very frequent [Orphanet] 52 / 7739
49
 (HPO:0000790) Hematuria 106 / 7739
50
 (HPO:0005575) Hemolytic-uremic syndrome 11 / 7739
51
 (HPO:0000112) Nephropathy 92 / 7739
52
 (HPO:0000083) Renal insufficiency 232 / 7739
53
 (HPO:0000093) Proteinuria 169 / 7739
54
 (HPO:0001873) Thrombocytopenia 224 / 7739
55
 (HPO:0003145) Decreased adenosylcobalamin 10 / 7739
56
 (HPO:0003223) Decreased methylcobalamin 11 / 7739
57
 (HPO:0000007) Autosomal recessive inheritance 2538 / 7739
58
 (HPO:0002120) Cerebral cortical atrophy 187 / 7739
59
 (HPO:0000238) Hydrocephalus Very frequent [Orphanet] 278 / 7739
60
 (HPO:0003593) Infantile onset Typical [HPO:probinson] 249 / 7739
61
 (OMIM) Acute neurologic decompensation (in later-onset cases) 1 / 7739
62
 (OMIM) Decreased cobalamin in liver, kidney, and cultured fibroblasts 1 / 7739
63
 (OMIM) Decreased cognition (later-onset) 1 / 7739
64
 (OMIM) Homocysteinemia 2 / 7739
65
 (OMIM) Normal serum cobalamin 7 / 7739
66
 (OMIM) Thrombotic microangiopathic nephropathy 1 / 7739
67
 (OMIM) Uremia 3 / 7739
68
 (OMIM) Vascular lesions 1 / 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 Mudd et al. (1969) reported an infant with homocysteinemia, methylmalonic aciduria, cystathioninemia, and a decrease in blood methionine. He died at 7.5 weeks of age. In vitro analysis identified a defect in the 2 reactions in which vitamin ...
Genotype-Phenotype Correlations OMIM Morel et al. (2006) reported genotype-phenotype correlations in 37 patients from published case reports, representing most of the landmark descriptions of cobalamin C deficiency. Twenty-five of 37 had early-onset disease, presenting in the first 6 months of life; ...
Molecular genetics OMIM Lerner-Ellis et al. (2006) refined the chromosomal map interval containing the mutation for methylmalonic aciduria and homocystinuria, cblC type, to a region of the short arm of chromosome 1 containing the MMACHC gene. In 204 individuals, 42 different ...