MMAHCC
MCID: MTH054
MIFTS: 46

Methylmalonic Aciduria and Homocystinuria, Cblc Type (MMAHCC) malady

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Eye diseases, Metabolic diseases, Blood diseases

Aliases & Classifications for Methylmalonic Aciduria and Homocystinuria, Cblc Type

Aliases & Descriptions for Methylmalonic Aciduria and Homocystinuria, Cblc Type:

Name: Methylmalonic Aciduria and Homocystinuria, Cblc Type 54 50 24 13
Methylmalonic Aciduria and Homocystinuria Type Cblc 12 66 14
Methylmalonic Acidemia and Homocystinuria Cblc Type 66 29
Cblc 50 24
Vitamin B12 Metabolic Defect with Combined Deficiency of Methylmalonyl-Coa Mutase and Homocysteine:methyltetrahydrofolate Methyltransferase 66
Combined Defect in Adenosylcobalamin and Methylcobalamin Synthesis, Type Cblc 56
Methylmalonic Aciduria and Homocystinuria Vitamin B12-Responsive 66
Methylmalonic Acidemia with Homocystinuria, Type Cblc 56
Methylmalonic Aciduria with Homocystinuria, Type Cblc 56
Methylmalonic Acidemia with Homocystinuria Type Cblc 50
Methylmalonic Acidemia and Homocystinuria, Cblc Type 24
Methylmalonic Acidemia and Homocystinuria Cblc 50
Methylmalonic Aciduria and Homocystinuria Cblc 50
Methylmalonic Acidemia with Homocystinuria 69
Cobalamin C Deficiency 12
Cobalamin C Disease 50
Cobalamin C Defect 56
Cblc Defect 56
Mmahcc 66

Characteristics:

Orphanet epidemiological data:

56
methylmalonic acidemia with homocystinuria, type cblc
Inheritance: Autosomal recessive; Age of onset: All ages; Age of death: any age;

HPO:

32
methylmalonic aciduria and homocystinuria, cblc type:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:



External Ids:

OMIM 54 277400
Disease Ontology 12 DOID:0050715
Orphanet 56 ORPHA79282
ICD10 via Orphanet 34 E72.1
MedGen 40 C1848561

Summaries for Methylmalonic Aciduria and Homocystinuria, Cblc Type

OMIM : 54 Combined methylmalonic aciduria (MMA) and homocystinuria is a genetically heterogeneous disorder of cobalamin (cbl;... (277400) more...

MalaCards based summary : Methylmalonic Aciduria and Homocystinuria, Cblc Type, also known as methylmalonic aciduria and homocystinuria type cblc, is related to mental retardation, x-linked 3 and methylmalonic acidemia with homocystinuria, and has symptoms including fatigue, seizures and lethargy. An important gene associated with Methylmalonic Aciduria and Homocystinuria, Cblc Type is MMACHC (Methylmalonic Aciduria (Cobalamin Deficiency) CblC Type, With Homocystinuria), and among its related pathways/superpathways are One carbon pool by folate and Folate Metabolism. The drugs Hydroxocobalamin and Cyanocobalamin have been mentioned in the context of this disorder. Affiliated tissues include bone, eye and bone marrow, and related phenotype is Synthetic lethal with Ras.

Disease Ontology : 12 A methylmalonic acidemia that has material basis in deficiency in synthesis of both AdoCbl and MeCbl (cblC) and is characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl), which results in decreased activity of the respective enzymes methylmalonyl-CoA mutase.

NIH Rare Diseases : 50 methylmalonic academia with homocystinuria (mma+hcu) cblc is a genetic disorder that prevents the body from breaking down certain amino acids found in protein (i.e., isoleucine, valine, methionine, and threonine). as a result, homocystine, methylmalonic acid, and other harmful substances build-up in the body. treatment should begin as soon as possible. in general, treatment may involve a low-protein diet, medical formula/drink, regular meals, careful monitoring, and vitamin b12 shots. most us states now offer newborn screening for mma+hcu, allowing for early detection and treatment. however even with early treatment, most children with mma+hcu experience some symptoms affecting vision, growth, and learning. mma+hcu cblc type is caused by changes in the mmachc gene. it is inherited in an autosomal recessive fashion. last updated: 6/11/2014

UniProtKB/Swiss-Prot : 66 Methylmalonic aciduria and homocystinuria type cblC: A disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). Affected individuals may have developmental, hematologic, neurologic, metabolic, ophthalmologic, and dermatologic clinical findings. Although considered a disease of infancy or childhood, some individuals develop symptoms in adulthood.

Related Diseases for Methylmalonic Aciduria and Homocystinuria, Cblc Type

Diseases related to Methylmalonic Aciduria and Homocystinuria, Cblc Type via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 36)
id Related Disease Score Top Affiliating Genes
1 mental retardation, x-linked 3 10.9
2 methylmalonic acidemia with homocystinuria 10.7
3 methylmalonic aciduria and homocystinuria, cbld type 10.7
4 methylmalonic aciduria, vitamin b12-responsive 10.7
5 methylmalonic aciduria, mut(0) type 10.7
6 methylmalonic aciduria and homocystinuria, cblf type 10.7
7 methylmalonic aciduria, vitamin b12-responsive, due to defect in synthesis of adenosylcobalamin, cblb complementation type 10.7
8 homocystinuria 10.7
9 ezh2-related overgrowth 10.2 MMACHC MTR
10 myh7-related myosin storage myopathy 10.2 CBS MTR
11 myosclerosis, congenital 10.2 CBS MTR
12 hyperekplexia 2, autosomal recessive 10.2 MMACHC MTR
13 deafness, autosomal recessive 45 10.2 MTHFD1 MTR
14 calcaneonavicular coalition 10.2 MMACHC MTR
15 coenzyme q10 deficiency disease 10.2 CBL MTR
16 neuropathy 10.2
17 anxiety disorder 10.2 MTHFD1 MTR
18 houlston ironton temple syndrome 10.1 CBS MMACHC MTR
19 aniseikonia 10.1 CBS PLG
20 cleft lip 10.1 CBS MMACHC MTR
21 autosomal dominant sideroblastic anemia 10.1 CBS MTHFD1 MTR
22 neurofibroma of the heart 10.1 CBS MTHFD1 MTR
23 septic myocarditis 10.0 ADAMTS13 CD46
24 pediatric mesenchymal chondrosarcoma 10.0 ADAMTS13 CBS
25 iridocyclitis 10.0 ADAMTS13 PLG
26 agammaglobulinemia 2 10.0 CBL MMD MTR
27 thyroid cancer, anaplastic 10.0 ADAMTS13 CD46
28 lip disease 9.9 MMD PLG
29 borderline glaucoma 9.9 CBS MMACHC MMD MTR
30 pentosuria 9.8 MMD PLG
31 chronic progressive external ophthalmoplegia 9.8 ADAMTS13 CD46 DGKE
32 myocardial infarction 9.8 ADAMTS13 CBS FABP3 PLG
33 hydrops fetalis 9.7
34 nephrotic syndrome 9.7
35 hemolytic-uremic syndrome 9.7
36 methylmalonic acidemia 9.7

Graphical network of the top 20 diseases related to Methylmalonic Aciduria and Homocystinuria, Cblc Type:



Diseases related to Methylmalonic Aciduria and Homocystinuria, Cblc Type

Symptoms & Phenotypes for Methylmalonic Aciduria and Homocystinuria, Cblc Type

Symptoms by clinical synopsis from OMIM:

277400

Clinical features from OMIM:

277400

Human phenotypes related to Methylmalonic Aciduria and Homocystinuria, Cblc Type:

56 32 (show all 49)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 fatigue 56 32 Very frequent (99-80%) HP:0012378
2 seizures 56 32 Very frequent (99-80%) HP:0001250
3 lethargy 56 32 Very frequent (99-80%) HP:0001254
4 hydrocephalus 56 32 Very frequent (99-80%) HP:0000238
5 failure to thrive 56 32 Very frequent (99-80%) HP:0001508
6 microcephaly 56 32 Very frequent (99-80%) HP:0000252
7 retinopathy 56 32 Very frequent (99-80%) HP:0000488
8 pallor 56 32 Very frequent (99-80%) HP:0000980
9 anorexia 56 32 Very frequent (99-80%) HP:0002039
10 megaloblastic bone marrow 56 32 Very frequent (99-80%) HP:0001980
11 tremor 32 HP:0001337
12 abnormality of extrapyramidal motor function 32 HP:0002071
13 low-set ears 32 HP:0000369
14 nystagmus 32 HP:0000639
15 intellectual disability 32 HP:0001249
16 muscular hypotonia 32 HP:0001252
17 macrotia 32 HP:0000400
18 global developmental delay 32 HP:0001263
19 smooth philtrum 32 HP:0000319
20 visual impairment 32 HP:0000505
21 feeding difficulties in infancy 32 HP:0008872
22 renal insufficiency 32 HP:0000083
23 proteinuria 32 HP:0000093
24 nephropathy 32 HP:0000112
25 thromboembolism 32 HP:0001907
26 reduced visual acuity 32 HP:0007663
27 thrombocytopenia 32 HP:0001873
28 cerebral cortical atrophy 32 HP:0002120
29 hematuria 32 HP:0000790
30 dementia 32 HP:0000726
31 long face 32 HP:0000276
32 neutropenia 32 HP:0001875
33 high forehead 32 HP:0000348
34 metabolic acidosis 32 HP:0001942
35 methylmalonic aciduria 32 HP:0012120
36 confusion 32 HP:0001289
37 pigmentary retinopathy 32 HP:0000580
38 megaloblastic anemia 32 HP:0001889
39 decreased methylcobalamin 32 HP:0003223
40 cystathioninuria 32 HP:0003153
41 hemolytic-uremic syndrome 32 HP:0005575
42 homocystinuria 32 HP:0002156
43 hyperhomocystinemia 32 HP:0002160
44 decreased methionine synthase activity 32 HP:0003524
45 hypomethioninemia 32 HP:0003658
46 methylmalonic acidemia 32 HP:0002912
47 decreased adenosylcobalamin 32 HP:0003145
48 decreased methylmalonyl-coa mutase activity 32 HP:0003210
49 cystathioninemia 32 HP:0003286

UMLS symptoms related to Methylmalonic Aciduria and Homocystinuria, Cblc Type:


lethargy, seizures

GenomeRNAi Phenotypes related to Methylmalonic Aciduria and Homocystinuria, Cblc Type according to GeneCards Suite gene sharing:

26
id Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Synthetic lethal with Ras GR00018-A-0 9.02 CBL CBS FABP3 MTR PLG

Drugs & Therapeutics for Methylmalonic Aciduria and Homocystinuria, Cblc Type

Drugs for Methylmalonic Aciduria and Homocystinuria, Cblc Type (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 16)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Hydroxocobalamin Approved Phase 2 13422-51-0 11953898 5460373 44475014
2
Cyanocobalamin Approved, Nutraceutical Phase 2 68-19-9 44176380
3
Folic Acid Approved, Nutraceutical, Vet_approved Phase 2 59-30-3 6037
4 Antioxidants Phase 2
5 Hematinics Phase 2
6 Micronutrients Phase 2
7 Trace Elements Phase 2
8 Ubiquinone Phase 2
9 Vitamin B 12 Phase 2
10 Vitamin B Complex Phase 2
11 Vitamins Phase 2
12
Cobalamin Nutraceutical Phase 2 13408-78-1 6438156
13 Folate Nutraceutical Phase 2
14
Methylcobalamin Experimental, Nutraceutical Phase 2 13422-55-4
15 Vitamin B12 Nutraceutical Phase 2
16 Vitamin B9 Nutraceutical Phase 2

Interventional clinical trials:


id Name Status NCT ID Phase
1 EPI-743 in Cobalamin C Defect: Effects on Visual and Neurological Impairment Completed NCT01793090 Phase 2

Search NIH Clinical Center for Methylmalonic Aciduria and Homocystinuria, Cblc Type

Genetic Tests for Methylmalonic Aciduria and Homocystinuria, Cblc Type

Genetic tests related to Methylmalonic Aciduria and Homocystinuria, Cblc Type:

id Genetic test Affiliating Genes
1 Methylmalonic Acidemia with Homocystinuria Cblc 29
2 Cblc 24 MMACHC

Anatomical Context for Methylmalonic Aciduria and Homocystinuria, Cblc Type

MalaCards organs/tissues related to Methylmalonic Aciduria and Homocystinuria, Cblc Type:

39
Bone, Eye, Bone Marrow

Publications for Methylmalonic Aciduria and Homocystinuria, Cblc Type

Articles related to Methylmalonic Aciduria and Homocystinuria, Cblc Type:

id Title Authors Year
1
Genetic analysis of four cases of methylmalonic aciduria and homocystinuria, cblC type(.). ( 26464686 )
2015
2
First Chinese case of successful pregnancy with combined methylmalonic aciduria and homocystinuria, cblC type. ( 24974159 )
2014
3
A clinical and gene analysis of late-onset combined methylmalonic aciduria and homocystinuria, cblC type, in China. ( 22560872 )
2012
4
Combined methylmalonic aciduria and homocystinuria cblC type of a Taiwanese infant with c.609G>A and C.567dupT mutations in the MMACHC gene. ( 21835369 )
2011
5
Newborn screening and early biochemical follow-up in combined methylmalonic aciduria and homocystinuria, cblC type, and utility of methionine as a secondary screening analyte. ( 19836982 )
2010
6
Early onset methylmalonic aciduria and homocystinuria cblC type with demyelinating neuropathy. ( 20610126 )
2010
7
Spectrum of MMACHC mutations in Italian and Portuguese patients with combined methylmalonic aciduria and homocystinuria, cblC type. ( 18164228 )
2008
8
Marfanoid features in a child with combined methylmalonic aciduria and homocystinuria (CblC type). ( 17768669 )
2007
9
DNA-based diagnosis of methylmalonic aciduria and homocystinuria, cblC type in a Chinese patient presenting with mild developmental delay. ( 16963011 )
2007
10
Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type. ( 16311595 )
2006

Variations for Methylmalonic Aciduria and Homocystinuria, Cblc Type

UniProtKB/Swiss-Prot genetic disease variations for Methylmalonic Aciduria and Homocystinuria, Cblc Type:

66 (show all 14)
id Symbol AA change Variation ID SNP ID
1 MMACHC p.Gln27Arg VAR_024770 rs546099787
2 MMACHC p.Leu116Pro VAR_024771 rs121918240
3 MMACHC p.His122Arg VAR_024772
4 MMACHC p.Tyr130His VAR_024773 rs372670428
5 MMACHC p.Gly147Ala VAR_024774 rs140522266
6 MMACHC p.Gly147Asp VAR_024775 rs140522266
7 MMACHC p.Gly156Asp VAR_024776
8 MMACHC p.Trp157Cys VAR_024777
9 MMACHC p.Arg161Gly VAR_024778
10 MMACHC p.Arg161Gln VAR_024779 rs121918243
11 MMACHC p.Arg189Ser VAR_024780 rs200895671
12 MMACHC p.Leu193Pro VAR_024781
13 MMACHC p.Arg206Pro VAR_024782
14 MMACHC p.Arg206Trp VAR_024783

ClinVar genetic disease variations for Methylmalonic Aciduria and Homocystinuria, Cblc Type:

6 (show all 15)
id Gene Variation Type Significance SNP ID Assembly Location
1 MMACHC NM_015506.2(MMACHC): c.271dupA (p.Arg91Lysfs) duplication Pathogenic rs398124292 GRCh38 Chromosome 1, 45507545: 45507545
2 MMACHC NM_015506.2(MMACHC): c.347T> C (p.Leu116Pro) single nucleotide variant Pathogenic rs121918240 GRCh37 Chromosome 1, 45973954: 45973954
3 MMACHC NM_015506.2(MMACHC): c.394C> T (p.Arg132Ter) single nucleotide variant Pathogenic rs121918241 GRCh37 Chromosome 1, 45974001: 45974001
4 MMACHC NM_015506.2(MMACHC): c.331C> T (p.Arg111Ter) single nucleotide variant Pathogenic rs121918242 GRCh37 Chromosome 1, 45973938: 45973938
5 MMACHC NM_015506.2(MMACHC): c.609G> A (p.Trp203Ter) single nucleotide variant Pathogenic rs587776889 GRCh37 Chromosome 1, 45974647: 45974647
6 MMACHC MMACHC, 3-BP DEL, 658AAG deletion Pathogenic
7 MMACHC NM_015506.2(MMACHC): c.481C> T (p.Arg161Ter) single nucleotide variant Pathogenic rs370596113 GRCh37 Chromosome 1, 45974519: 45974519
8 MMACHC NM_015506.2(MMACHC): c.547_548delGT (p.Val183Thrfs) deletion Pathogenic rs398124293 GRCh37 Chromosome 1, 45974585: 45974586
9 MMACHC NM_015506.2(MMACHC): c.608G> A (p.Trp203Ter) single nucleotide variant Pathogenic rs398124295 GRCh37 Chromosome 1, 45974646: 45974646
10 MMACHC NM_015506.2(MMACHC): c.658_660delAAG (p.Lys220del) deletion Pathogenic rs398124296 GRCh37 Chromosome 1, 45974696: 45974698
11 MMACHC NM_015506.2(MMACHC): c.276G> T (p.Glu92Asp) single nucleotide variant Pathogenic rs556977618 GRCh37 Chromosome 1, 45973222: 45973222
12 MMACHC NM_015506.2(MMACHC): c.276G> A (p.Glu92=) single nucleotide variant Pathogenic rs556977618 GRCh37 Chromosome 1, 45973222: 45973222
13 MMACHC NM_015506.2(MMACHC): c.464G> A (p.Gly155Glu) single nucleotide variant Pathogenic rs606231425 GRCh37 Chromosome 1, 45974502: 45974502
14 MMACHC NM_015506.2(MMACHC): c.615C> G (p.Tyr205Ter) single nucleotide variant Pathogenic rs747527726 GRCh37 Chromosome 1, 45974653: 45974653
15 MMACHC NM_015506.2(MMACHC): c.270dupT (p.Arg91Terfs) duplication Pathogenic GRCh37 Chromosome 1, 45973216: 45973216

Expression for Methylmalonic Aciduria and Homocystinuria, Cblc Type

Search GEO for disease gene expression data for Methylmalonic Aciduria and Homocystinuria, Cblc Type.

Pathways for Methylmalonic Aciduria and Homocystinuria, Cblc Type

GO Terms for Methylmalonic Aciduria and Homocystinuria, Cblc Type

Biological processes related to Methylmalonic Aciduria and Homocystinuria, Cblc Type according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 hemostasis GO:0007599 9.32 ADAMTS13 PLG
2 cobalamin metabolic process GO:0009235 9.26 MMACHC MTR
3 methionine biosynthetic process GO:0009086 9.16 MTHFD1 MTR
4 transsulfuration GO:0019346 8.96 CBS MTHFD1
5 cellular amino acid biosynthetic process GO:0008652 8.8 CBS MTHFD1 MTR

Molecular functions related to Methylmalonic Aciduria and Homocystinuria, Cblc Type according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 cobalamin binding GO:0031419 8.62 MMACHC MTR

Sources for Methylmalonic Aciduria and Homocystinuria, Cblc Type

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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