MCID: MTH055
MIFTS: 32

Methylmalonic Aciduria and Homocystinuria, Cbld Type

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

Aliases & Classifications for Methylmalonic Aciduria and Homocystinuria, Cbld Type

MalaCards integrated aliases for Methylmalonic Aciduria and Homocystinuria, Cbld Type:

Name: Methylmalonic Aciduria and Homocystinuria, Cbld Type 54
Homocystinuria, Cbld Type, Variant 1 54 29 13
Methylmalonic Aciduria and Homocystinuria Type Cbld 12 71
Methylmalonic Aciduria, Cbld Type, Variant 2 54 29
Combined Defect in Adenosylcobalamin and Methylcobalamin Synthesis, Type Cbld 56
Vitamin B12-Responsive Methylmalonic Acidemia, Type Cbldv2 56
Vitamin B12-Responsive Methylmalonic Aciduria, Type Cbldv2 56
Methylmalonic Aciduria and Homocystinuria Cbld Original 71
Methylmalonic Aciduria and Homocystinuria Cbld-Combined 71
Methylmalonic Acidemia with Homocystinuria, Type Cbld 56
Methylmalonic Aciduria with Homocystinuria, Type Cbld 56
Functional Methionine Synthase Deficiency Type Cbldv1 56
Methylmalonic Acidemia and Homocystinuria Cbld Type 71
Methylmalonic Acidemia with Homocystinuria Cbld 29
Methylcobalamin Deficiency Type Cbldv1 56
Methylmalonic Aciduria Cbld Variant 2 71
Homocystinuria Cbld Variant 1 71
Cobalamin D Deficiency 12
Cobalamin D Defect 56
Cbld Defect 56
Mmahcd 71

Characteristics:

Orphanet epidemiological data:

56
methylmalonic acidemia with homocystinuria, type cbld
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: All ages;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
good response to vitamin b12 therapy 'variant 1' has isolated homocystinuria and decreased mecbl
'variant 2' has isolated methylmalonicaciduria and decreased adocbl


HPO:

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


Classifications:



Summaries for Methylmalonic Aciduria and Homocystinuria, Cbld Type

OMIM : 54
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 enzymes methylmalonyl-CoA mutase (MUT; 609058) and methyltetrahydrofolate:homocysteine methyltransferase, also known as methionine synthase (MTR; 156570). Different forms of the disorder have been classified according to complementation groups of cells in vitro: cblC (277400), cblD, and cblF (277380). Isolated methylmalonic acidurias have also been classified by complementation groups: MMA 'mut' (251000), caused by mutation in the MUT gene on chromosome 6p21; MMA cblA (251100), caused by mutation in the MMAA gene (607481) on 4q31; and MMA cblB (251110), caused by mutation in the MMAB gene (607568) on 12q24. Another form of isolated MMA (613646) can be caused by defect in the transcobalamin receptor (CD320; 606475). (277410)

MalaCards based summary : Methylmalonic Aciduria and Homocystinuria, Cbld Type, also known as homocystinuria, cbld type, variant 1, is related to methylmalonic acidemia with homocystinuria type cbld and cholestasis, progressive familial intrahepatic 2, and has symptoms including seizures, lethargy and global developmental delay. An important gene associated with Methylmalonic Aciduria and Homocystinuria, Cbld Type is MMADHC (Methylmalonic Aciduria And Homocystinuria, CblD Type). Affiliated tissues include bone and bone marrow.

UniProtKB/Swiss-Prot : 71 Methylmalonic aciduria and homocystinuria type cblD: A disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). Clinical features include developmental delay, hyotonia, mental retardation, seizures, megaloblastic anemia. Some patients manifest combined methylmalonic aciduria and homocystinuria (referred to as cblD original), some have only isolated homocystinuria (cblD variant 1), and others have only methylmalonic aciduria (cblD variant 2).

Disease Ontology : 12 A methylmalonic aciduria that is characterized by combined homocystinuria and methylmalonic aciduria and deficiency of MCM and MS activities.

Related Diseases for Methylmalonic Aciduria and Homocystinuria, Cbld Type

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

id Related Disease Score Top Affiliating Genes
1 methylmalonic acidemia with homocystinuria type cbld 11.4
2 cholestasis, progressive familial intrahepatic 2 8.9 LOC100216355 LOC100216356 MMADHC

Symptoms & Phenotypes for Methylmalonic Aciduria and Homocystinuria, Cbld Type

Symptoms via clinical synopsis from OMIM:

54

Neurologic- Central Nervous System:
hypotonia
mental retardation
dystonia
developmental delay
seizures
more
Hematology:
megaloblastic anemia
increased mean corpuscular volume

Head And Neck- Eyes:
nystagmus

Laboratory- Abnormalities:
homocystinuria
methylmalonic aciduria
methylmalonic acidemia
decreased serum methionine
decreased methylmalonyl-coa mutase (mut, ) activity
more

Clinical features from OMIM:

277410

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

56 32 (show all 28)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 56 32 Very frequent (99-80%) HP:0001250
2 lethargy 56 32 Very frequent (99-80%) HP:0001254
3 global developmental delay 56 32 Very frequent (99-80%) HP:0001263
4 intellectual disability 56 32 Very frequent (99-80%) HP:0001249
5 failure to thrive 56 Very frequent (99-80%)
6 nystagmus 32 HP:0000639
7 dystonia 32 HP:0001332
8 megaloblastic anemia 32 HP:0001889
9 homocystinuria 32 HP:0002156
10 methylmalonic aciduria 32 HP:0012120
11 methylmalonic acidemia 32 HP:0002912
12 fatigue 56 Very frequent (99-80%)
13 cerebral cortical atrophy 32 HP:0002120
14 hyperhomocystinemia 32 HP:0002160
15 hypomethioninemia 32 HP:0003658
16 muscular hypotonia 32 HP:0001252
17 spastic ataxia 32 HP:0002497
18 increased mean corpuscular volume 32 HP:0005518
19 gait disturbance 56 Very frequent (99-80%)
20 pallor 56 Very frequent (99-80%)
21 anorexia 56 Very frequent (99-80%)
22 megaloblastic bone marrow 56 Very frequent (99-80%)
23 behavioral abnormality 56 Very frequent (99-80%)
24 abnormality of movement 56 Very frequent (99-80%)
25 decreased methylcobalamin 32 HP:0003223
26 decreased methionine synthase activity 32 HP:0003524
27 decreased adenosylcobalamin 32 HP:0003145
28 decreased methylmalonyl-coa mutase activity 32 HP:0003210

Drugs & Therapeutics for Methylmalonic Aciduria and Homocystinuria, Cbld Type

Search Clinical Trials , NIH Clinical Center for Methylmalonic Aciduria and Homocystinuria, Cbld Type

Genetic Tests for Methylmalonic Aciduria and Homocystinuria, Cbld Type

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

id Genetic test Affiliating Genes
1 Homocystinuria, Cbld Type, Variant 1 29
2 Methylmalonic Acidemia with Homocystinuria Cbld 29
3 Methylmalonic Aciduria, Cbld Type, Variant 2 29

Anatomical Context for Methylmalonic Aciduria and Homocystinuria, Cbld Type

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

39
Bone, Bone Marrow

Publications for Methylmalonic Aciduria and Homocystinuria, Cbld Type

Variations for Methylmalonic Aciduria and Homocystinuria, Cbld Type

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

71
id Symbol AA change Variation ID SNP ID
1 MMADHC p.Thr182Asn VAR_043844 rs118204045
2 MMADHC p.Tyr249Cys VAR_043846 rs118204046
3 MMADHC p.Leu259Pro VAR_043847 rs118204044

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

6 (show all 13)
id Gene Variation Type Significance SNP ID Assembly Location
1 MMADHC NM_015702.2(MMADHC): c.776T> C (p.Leu259Pro) single nucleotide variant Pathogenic rs118204044 GRCh37 Chromosome 2, 150426603: 150426603
2 MMADHC NM_015702.2(MMADHC): c.545C> A (p.Thr182Asn) single nucleotide variant Pathogenic rs118204045 GRCh37 Chromosome 2, 150432289: 150432289
3 MMADHC NM_015702.2(MMADHC): c.746A> G (p.Tyr249Cys) single nucleotide variant Pathogenic rs118204046 GRCh37 Chromosome 2, 150426633: 150426633
4 MMADHC NM_015702.2(MMADHC): c.57_64delCTCTTTAG (p.Ser20Terfs) deletion Pathogenic rs397509361 GRCh37 Chromosome 2, 150438731: 150438738
5 MMADHC NM_015702.2(MMADHC): c.160C> T (p.Arg54Ter) single nucleotide variant Pathogenic rs118204047 GRCh37 Chromosome 2, 150436157: 150436157
6 MMADHC NM_015702.2(MMADHC): c.307_324dup18 (p.Ser108_Ser109insLeuAlaGluProLeuSer) duplication Pathogenic rs397509362 GRCh37 Chromosome 2, 150435993: 150436010
7 MMADHC NM_015702.2(MMADHC): c.748C> T (p.Arg250Ter) single nucleotide variant Pathogenic rs118204048 GRCh37 Chromosome 2, 150426631: 150426631
8 MMADHC NM_015702.2(MMADHC): c.419dupA (p.Tyr140Terfs) duplication Pathogenic rs397509363 GRCh37 Chromosome 2, 150433010: 150433010
9 MMADHC NM_015702.2(MMADHC): c.696+3_696+6del deletion Pathogenic rs397509364 GRCh37 Chromosome 2, 150427593: 150427596
10 MMADHC NM_015702.2(MMADHC): c.455dupC (p.Cys153Metfs) duplication Pathogenic rs864309743 GRCh37 Chromosome 2, 150432974: 150432974
11 MMADHC NM_015702.2(MMADHC): c.228dupG (p.Asn77Glufs) duplication Pathogenic rs864309741 GRCh37 Chromosome 2, 150436089: 150436089
12 MMADHC NM_015702.2(MMADHC): c.133dupG (p.Ala45Glyfs) duplication Pathogenic rs864309740 GRCh37 Chromosome 2, 150438662: 150438662
13 MMADHC NM_015702.2(MMADHC): c.60_61insAT (p.Leu21Ilefs) insertion Pathogenic rs864309742 GRCh38 Chromosome 2, 149582220: 149582221

Expression for Methylmalonic Aciduria and Homocystinuria, Cbld Type

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

Pathways for Methylmalonic Aciduria and Homocystinuria, Cbld Type

GO Terms for Methylmalonic Aciduria and Homocystinuria, Cbld Type

Sources for Methylmalonic Aciduria and Homocystinuria, Cbld Type

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