MMAB
MCID: MTH078
MIFTS: 47

Methylmalonic Aciduria, Cblb Type (MMAB)

Categories: Genetic diseases, Liver diseases, Metabolic diseases, Nephrological diseases, Rare diseases

Aliases & Classifications for Methylmalonic Aciduria, Cblb Type

MalaCards integrated aliases for Methylmalonic Aciduria, Cblb Type:

Name: Methylmalonic Aciduria, Cblb Type 57 53
Methylmalonic Aciduria Cblb Type 12 53 29 6 73
Methylmalonic Aciduria, Vitamin B12-Responsive, Due to Defect in Synthesis of Adenosylcobalamin, Cblb Complementation Type 57 12 13
Methylmalonic Acidemia Cblb Type 12 53 15
Methylmalonic Aciduria, Vitamin B12-Responsive, Due to Defect in Synthesis of Adenosylcobalamin, Cblb Type 57 53
Vitamin B12-Responsive Methylmalonic Aciduria, Type Cblb 53 59
Vitamin B12-Responsive Methylmalonic Acidemia Type Cblb 53 59
Methylmalonic Acidemia, Cblb Type 57 53
Vitamin B12 Responsive Methylmalonic Acidemia Type Cbl B 75
Vitamin B12 Responsive Methylmalonic Aciduria Type Cbl B 75
Methylmalonic Aciduria Type Cblb 75
Methylmalonic Aciduria Type B 75
Methylmalonic Acidemia 73
Methylmalonic Aciduria 73
Mmab 75

Characteristics:

Orphanet epidemiological data:

59
vitamin b12-responsive methylmalonic acidemia type cblb
Inheritance: Autosomal recessive; Age of onset: Childhood;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
neonatal onset
a subset of patients are responsive to vitamin b12 therapy
some patients may be asymptomatic if diagnosed early and properly managed during metabolic crises


HPO:

32
methylmalonic aciduria, cblb type:
Onset and clinical course neonatal onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Methylmalonic Aciduria, Cblb Type

NIH Rare Diseases : 53 Methylmalonic aciduria, cblB type is an inherited condition in which the body is unable to metabolize certain proteins and fats properly. Signs and symptoms generally develop in the first few months of life and may include failure to thrive, lethargy, vomiting, dehydration, hypotonia, developmental delay, seizures, ataxia (problems with muscle control), feeding difficulties, and an enlarged liver (hepatomegaly). Intellectual disability is a long-term consequence. Methylmalonic aciduria, cblB type is caused by changes (mutations) in the MMAB gene and is inherited in an autosomal recessive manner. There is no cure for the condition. Treatments are focused on alleviating some of the associated symptoms and may include a special diet and various medications and/or supplements.

MalaCards based summary : Methylmalonic Aciduria, Cblb Type, also known as methylmalonic aciduria cblb type, is related to mevalonic aciduria and methylmalonic aciduria due to methylmalonyl-coa mutase deficiency, and has symptoms including vomiting, respiratory distress and lethargy. An important gene associated with Methylmalonic Aciduria, Cblb Type is MMAB (Metabolism Of Cobalamin Associated B), and among its related pathways/superpathways are Metabolism of water-soluble vitamins and cofactors and Regulation of Wnt-mediated beta catenin signaling and target gene transcription. Affiliated tissues include liver and heart, and related phenotypes are muscular hypotonia and failure to thrive

Disease Ontology : 12 A methylmalonic acidemia characterized by autosomal recessive inheritance, defects in the synthesis of AdoCbl, vitamin B12 therapy responsiveness and that has material basis in homozygous or compound heterozygous mutation in the MMAB gene on chromosome 12q24.

OMIM : 57 Methylmalonic aciduria is a genetically heterogeneous disorder of methylmalonate and cobalamin (cbl; vitamin B12) metabolism. Different forms of isolated methylmalonic aciduria have been classified according to complementation groups of cells in vitro. Patients with defects in the synthesis of AdoCbl are usually responsive to vitamin B12 therapy and are classified as 'cbl' type: these include cblB and cblA (251100). The cblA type is caused by mutation in the MMAA gene (607481). The 'mut' type (251000) is caused by mutation in the MUT gene; in general, the mut form of MMA is unresponsive to vitamin B12 therapy. Combined methylmalonic aciduria and homocystinuria may be seen in complementation groups cblC (277400), cblD (277410), and cblF (277380). (251110)

UniProtKB/Swiss-Prot : 75 Methylmalonic aciduria type cblB: A disorder of methylmalonate and cobalamin metabolism due to defective synthesis of adenosylcobalamin.

Related Diseases for Methylmalonic Aciduria, Cblb Type

Graphical network of the top 20 diseases related to Methylmalonic Aciduria, Cblb Type:



Diseases related to Methylmalonic Aciduria, Cblb Type

Symptoms & Phenotypes for Methylmalonic Aciduria, Cblb Type

Symptoms via clinical synopsis from OMIM:

57
Growth Other:
failure to thrive

Metabolic Features:
dehydration
metabolic acidosis
ketosis

Hematology:
anemia
thrombocytopenia
neutropenia
pancytopenia (in 50% of patients)

Neurologic Central Nervous System:
coma
lethargy
developmental delay
hypotonia

Abdomen Liver:
hepatomegaly

Abdomen Gastrointestinal:
vomiting
poor feeding

Respiratory:
respiratory distress

Laboratory Abnormalities:
hyperammonemia
methylmalonic aciduria
ketonuria
hyperglycinemia
methylmalonic acidemia
more

Clinical features from OMIM:

251110

Human phenotypes related to Methylmalonic Aciduria, Cblb Type:

32 (show all 24)
# Description HPO Frequency HPO Source Accession
1 muscular hypotonia 32 HP:0001252
2 failure to thrive 32 HP:0001508
3 global developmental delay 32 HP:0001263
4 hepatomegaly 32 HP:0002240
5 feeding difficulties in infancy 32 HP:0008872
6 dehydration 32 HP:0001944
7 vomiting 32 HP:0002013
8 anemia 32 HP:0001903
9 pancytopenia 32 HP:0001876
10 respiratory distress 32 HP:0002098
11 thrombocytopenia 32 HP:0001873
12 coma 32 HP:0001259
13 neutropenia 32 HP:0001875
14 hyperammonemia 32 HP:0001987
15 lethargy 32 HP:0001254
16 metabolic acidosis 32 HP:0001942
17 generalized hypotonia 32 HP:0001290
18 methylmalonic aciduria 32 HP:0012120
19 ketonuria 32 HP:0002919
20 ketosis 32 HP:0001946
21 hyperglycinemia 32 HP:0002154
22 methylmalonic acidemia 32 HP:0002912
23 decreased adenosylcobalamin 32 HP:0003145
24 decreased methylmalonyl-coa mutase activity 32 HP:0003210

UMLS symptoms related to Methylmalonic Aciduria, Cblb Type:


vomiting, respiratory distress, lethargy

Drugs & Therapeutics for Methylmalonic Aciduria, Cblb Type

Search Clinical Trials , NIH Clinical Center for Methylmalonic Aciduria, Cblb Type

Genetic Tests for Methylmalonic Aciduria, Cblb Type

Genetic tests related to Methylmalonic Aciduria, Cblb Type:

# Genetic test Affiliating Genes
1 Methylmalonic Aciduria Cblb Type 29 MMAB

Anatomical Context for Methylmalonic Aciduria, Cblb Type

MalaCards organs/tissues related to Methylmalonic Aciduria, Cblb Type:

41
Liver, Heart

Publications for Methylmalonic Aciduria, Cblb Type

Articles related to Methylmalonic Aciduria, Cblb Type:

# Title Authors Year
1
New perspectives for pharmacological chaperoning treatment in methylmalonic aciduria cblB type. ( 29197662 )
2018
2
Methylmalonic aciduria cblB type: characterization of two novel mutations and mitochondrial dysfunction studies. ( 24813872 )
2015
3
Pharmacological chaperones as a potential therapeutic option in methylmalonic aciduria cblB type. ( 23674520 )
2013
4
Functional and structural analysis of five mutations identified in methylmalonic aciduria cblB type. ( 20556797 )
2010
5
Different altered pattern expression of genes related to apoptosis in isolated methylmalonic aciduria cblB type and combined with homocystinuria cblC type. ( 20696242 )
2010

Variations for Methylmalonic Aciduria, Cblb Type

UniProtKB/Swiss-Prot genetic disease variations for Methylmalonic Aciduria, Cblb Type:

75
# Symbol AA change Variation ID SNP ID
1 MMAB p.Ala135Thr VAR_017204 rs35648932
2 MMAB p.Arg186Trp VAR_017205 rs28941784
3 MMAB p.Arg191Trp VAR_017206 rs376128990
4 MMAB p.Glu193Lys VAR_017207 rs749758687
5 MMAB p.Ile96Thr VAR_023471 rs864309509

ClinVar genetic disease variations for Methylmalonic Aciduria, Cblb Type:

6 (show top 50) (show all 105)
# Gene Variation Type Significance SNP ID Assembly Location
1 MMAB NM_052845.3(MMAB): c.556C> T (p.Arg186Trp) single nucleotide variant Pathogenic rs28941784 GRCh37 Chromosome 12, 109998873: 109998873
2 MMAB NM_052845.3(MMAB): c.556C> T (p.Arg186Trp) single nucleotide variant Pathogenic rs28941784 GRCh38 Chromosome 12, 109561068: 109561068
3 MMAB NM_052845.3: c.573_577delGGCCG deletion Pathogenic
4 MMAB; MVK NM_052845.3(MMAB): c.288T> C (p.Ile96=) single nucleotide variant Benign/Likely benign rs62000414 GRCh37 Chromosome 12, 110006577: 110006577
5 MMAB; MVK NM_052845.3(MMAB): c.288T> C (p.Ile96=) single nucleotide variant Benign/Likely benign rs62000414 GRCh38 Chromosome 12, 109568772: 109568772
6 MMAB NM_052845.3(MMAB): c.568C> T (p.Arg190Cys) single nucleotide variant Pathogenic rs398124434 GRCh37 Chromosome 12, 109998861: 109998861
7 MMAB NM_052845.3(MMAB): c.568C> T (p.Arg190Cys) single nucleotide variant Pathogenic rs398124434 GRCh38 Chromosome 12, 109561056: 109561056
8 MMAB NM_052845.3(MMAB): c.716T> A (p.Met239Lys) single nucleotide variant Benign rs9593 GRCh37 Chromosome 12, 109994870: 109994870
9 MMAB NM_052845.3(MMAB): c.716T> A (p.Met239Lys) single nucleotide variant Benign rs9593 GRCh38 Chromosome 12, 109557065: 109557065
10 MMAB NM_052845.3(MMAB): c.700C> T (p.Gln234Ter) single nucleotide variant Pathogenic rs369296618 GRCh37 Chromosome 12, 109994886: 109994886
11 MMAB NM_052845.3(MMAB): c.700C> T (p.Gln234Ter) single nucleotide variant Pathogenic rs369296618 GRCh38 Chromosome 12, 109557081: 109557081
12 MMAB NM_052845.3(MMAB): c.563_577dupTGTGCCGCCGGGCCG (p.Ala192_Glu193insValCysArgArgAla) duplication Pathogenic/Likely pathogenic rs747499304 GRCh37 Chromosome 12, 109998852: 109998866
13 MMAB NM_052845.3(MMAB): c.563_577dupTGTGCCGCCGGGCCG (p.Ala192_Glu193insValCysArgArgAla) duplication Pathogenic/Likely pathogenic rs747499304 GRCh38 Chromosome 12, 109561047: 109561061
14 MMAB NM_052845.3(MMAB): c.569G> A (p.Arg190His) single nucleotide variant Pathogenic/Likely pathogenic rs756414548 GRCh38 Chromosome 12, 109561055: 109561055
15 MMAB NM_052845.3(MMAB): c.569G> A (p.Arg190His) single nucleotide variant Pathogenic/Likely pathogenic rs756414548 GRCh37 Chromosome 12, 109998860: 109998860
16 MMAB NM_052845.3(MMAB): c.185C> T (p.Thr62Met) single nucleotide variant Benign/Likely benign rs115802744 GRCh37 Chromosome 12, 110009465: 110009465
17 MMAB NM_052845.3(MMAB): c.185C> T (p.Thr62Met) single nucleotide variant Benign/Likely benign rs115802744 GRCh38 Chromosome 12, 109571660: 109571660
18 MMAA NM_172250.2(MMAA): c.370C> T (p.Gln124Ter) single nucleotide variant not provided rs796064514 GRCh38 Chromosome 4, 145639509: 145639509
19 MMAA NM_172250.2(MMAA): c.370C> T (p.Gln124Ter) single nucleotide variant not provided rs796064514 GRCh37 Chromosome 4, 146560661: 146560661
20 MMAB NM_052845.3(MMAB): c.37_54del18 (p.Gly13_Leu18del) deletion Uncertain significance rs770077320 GRCh38 Chromosome 12, 109573427: 109573444
21 MMAB NM_052845.3(MMAB): c.37_54del18 (p.Gly13_Leu18del) deletion Uncertain significance rs770077320 GRCh37 Chromosome 12, 110011232: 110011249
22 MMAB NM_052845.3(MMAB): c.520_584del65 single nucleotide variant Pathogenic rs756195708 GRCh38 Chromosome 12, 109561040: 109561040
23 MMAB NM_052845.3(MMAB): c.520_584del65 single nucleotide variant Pathogenic rs756195708 GRCh37 Chromosome 12, 109998845: 109998845
24 MMAB NM_052845.3(MMAB): c.287T> C (p.Ile96Thr) single nucleotide variant Pathogenic rs864309509 GRCh37 Chromosome 12, 110006578: 110006578
25 MMAB NM_052845.3(MMAB): c.287T> C (p.Ile96Thr) single nucleotide variant Pathogenic rs864309509 GRCh38 Chromosome 12, 109568773: 109568773
26 MMAB NM_052845.3(MMAB): c.571C> T (p.Arg191Trp) single nucleotide variant Pathogenic/Likely pathogenic rs376128990 GRCh38 Chromosome 12, 109561053: 109561053
27 MMAB NM_052845.3(MMAB): c.571C> T (p.Arg191Trp) single nucleotide variant Pathogenic/Likely pathogenic rs376128990 GRCh37 Chromosome 12, 109998858: 109998858
28 MMAB NM_052845.3(MMAB): c.349_354delATCCAG single nucleotide variant Likely pathogenic rs864309510 GRCh38 Chromosome 12, 109561853: 109561853
29 MMAB NM_052845.3(MMAB): c.349_354delATCCAG single nucleotide variant Likely pathogenic rs864309510 GRCh37 Chromosome 12, 109999658: 109999658
30 MMAB NM_052845.3(MMAB): c.197_290del94 single nucleotide variant Pathogenic rs864309511 GRCh38 Chromosome 12, 109568770: 109568770
31 MMAB NM_052845.3(MMAB): c.197_290del94 single nucleotide variant Pathogenic rs864309511 GRCh37 Chromosome 12, 110006575: 110006575
32 MMAB NM_052845.3(MMAB): c.570_572dupCCG (p.Arg191_Ala192insArg) duplication Pathogenic rs864309512 GRCh37 Chromosome 12, 109998857: 109998859
33 MMAB NM_052845.3(MMAB): c.570_572dupCCG (p.Arg191_Ala192insArg) duplication Pathogenic rs864309512 GRCh38 Chromosome 12, 109561052: 109561054
34 MMAB NM_052845.3(MMAB): c.548A> T (p.His183Leu) single nucleotide variant Uncertain significance rs752866643 GRCh37 Chromosome 12, 109998881: 109998881
35 MMAB NM_052845.3(MMAB): c.548A> T (p.His183Leu) single nucleotide variant Uncertain significance rs752866643 GRCh38 Chromosome 12, 109561076: 109561076
36 MMAB NM_052845.3(MMAB): c.656A> G (p.Tyr219Cys) single nucleotide variant Uncertain significance rs765547005 GRCh38 Chromosome 12, 109557125: 109557125
37 MMAB NM_052845.3(MMAB): c.656A> G (p.Tyr219Cys) single nucleotide variant Uncertain significance rs765547005 GRCh37 Chromosome 12, 109994930: 109994930
38 MMAB NM_052845.3(MMAB): c.572G> A (p.Arg191Gln) single nucleotide variant Pathogenic rs746219370 GRCh37 Chromosome 12, 109998857: 109998857
39 MMAB NM_052845.3(MMAB): c.572G> A (p.Arg191Gln) single nucleotide variant Pathogenic rs746219370 GRCh38 Chromosome 12, 109561052: 109561052
40 MMAB NM_052845.3(MMAB): c.403G> A (p.Ala135Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs35648932 GRCh37 Chromosome 12, 109999603: 109999603
41 MMAB NM_052845.3(MMAB): c.403G> A (p.Ala135Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs35648932 GRCh38 Chromosome 12, 109561798: 109561798
42 MMAB NM_052845.3(MMAB): c.291-1G> A single nucleotide variant Pathogenic/Likely pathogenic rs199971687 GRCh38 Chromosome 12, 109565177: 109565177
43 MMAB NM_052845.3(MMAB): c.291-1G> A single nucleotide variant Pathogenic/Likely pathogenic rs199971687 GRCh37 Chromosome 12, 110002982: 110002982
44 MMAB NM_052845.3(MMAB): c.197-1G> T single nucleotide variant Pathogenic rs763935916 GRCh38 Chromosome 12, 109568864: 109568864
45 MMAB NM_052845.3(MMAB): c.197-1G> T single nucleotide variant Pathogenic rs763935916 GRCh37 Chromosome 12, 110006669: 110006669
46 MMAB NM_052845.3(MMAB): c.56_57delGCinsAA (p.Arg19Gln) indel Benign/Likely benign rs36013132 GRCh38 Chromosome 12, 109573424: 109573425
47 MMAB NM_052845.3(MMAB): c.56_57delGCinsAA (p.Arg19Gln) indel Benign/Likely benign rs36013132 GRCh37 Chromosome 12, 110011229: 110011230
48 MMAB NM_052845.3(MMAB): c.563T> G (p.Val188Gly) single nucleotide variant Pathogenic rs869320654 GRCh38 Chromosome 12, 109561061: 109561061
49 MMAB NM_052845.3(MMAB): c.563T> G (p.Val188Gly) single nucleotide variant Pathogenic rs869320654 GRCh37 Chromosome 12, 109998866: 109998866
50 MMAB NM_052845.3(MMAB): c.2T> C (p.Met1Thr) single nucleotide variant Pathogenic rs869320655 GRCh37 Chromosome 12, 110011284: 110011284

Expression for Methylmalonic Aciduria, Cblb Type

Search GEO for disease gene expression data for Methylmalonic Aciduria, Cblb Type.

Pathways for Methylmalonic Aciduria, Cblb Type

GO Terms for Methylmalonic Aciduria, Cblb Type

Cellular components related to Methylmalonic Aciduria, Cblb Type according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nuclear transcription factor complex GO:0044798 8.62 KLF4 SOX2

Biological processes related to Methylmalonic Aciduria, Cblb Type according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of gene expression GO:0010629 9.58 ACACB KLF4 MYC
2 response to wounding GO:0009611 9.49 MYC SOX2
3 cellular response to organic cyclic compound GO:0071407 9.48 KLF4 MYC
4 cellular response to retinoic acid GO:0071300 9.46 KLF4 MYC
5 somatic stem cell population maintenance GO:0035019 9.43 KLF4 SOX2
6 positive regulation of telomerase activity GO:0051973 9.37 KLF4 MYC
7 regulation of cholesterol biosynthetic process GO:0045540 9.32 ACACB MVK
8 cobalamin metabolic process GO:0009235 9.26 MMAA MMAB
9 response to growth factor GO:0070848 9.16 MYC SOX2
10 cellular response to cycloheximide GO:0071409 8.96 KLF4 MYC
11 cobalamin biosynthetic process GO:0009236 8.62 MMAA MMAB

Molecular functions related to Methylmalonic Aciduria, Cblb Type according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 proximal promoter DNA-binding transcription activator activity, RNA polymerase II-specific GO:0001077 8.8 KLF4 MYC SOX2

Sources for Methylmalonic Aciduria, Cblb Type

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 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 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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