MCID: MTH055
MIFTS: 35

Methylmalonic Aciduria and Homocystinuria, Cbld Type

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Nephrological diseases, Metabolic diseases, Blood 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 53
Methylmalonic Aciduria and Homocystinuria Type Cbld 12 71 14
Homocystinuria, Cbld Type, Variant 1 53 28 13
Combined Defect in Adenosylcobalamin and Methylcobalamin Synthesis, Type Cbld 49 55
Methylmalonic Acidemia with Homocystinuria, Type Cbld 49 55
Methylmalonic Aciduria with Homocystinuria, Type Cbld 49 55
Methylmalonic Acidemia and Homocystinuria, Cbld Type 53 49
Methylmalonic Aciduria, Cbld Type, Variant 2 53 28
Methylmalonic Aciduria, Cblh Type, Formerly 53 49
Methylmalonic Acidemia, Cblh Type, Formerly 53 49
Cobalamin D Defect 49 55
Cbld Defect 49 55
Vitamin B12-Responsive Methylmalonic Acidemia, Type Cbldv2 55
Vitamin B12-Responsive Methylmalonic Aciduria, Type Cbldv2 55
Methylmalonic Aciduria and Homocystinuria Cbld-Combined 71
Methylmalonic Aciduria and Homocystinuria Cbld Original 71
Methylmalonic Aciduria, Cbld Type, Variant 2, Included 49
Functional Methionine Synthase Deficiency Type Cbldv1 55
Methylmalonic Acidemia with Homocystinuria Type Cbld 49
Methylmalonic Acidemia and Homocystinuria Cbld Type 71
Mehtylmalonic Acidemia with Homocystinuria Cbi D 49
Methylmalonic Acidemia with Homocystinuria Cbld 28
Homocystinuria, Cbld Type, Variant 1, Included 49
Methylcobalamin Deficiency Type Cbldv1 55
Methylmalonic Aciduria Cbld Variant 2 71
Homocystinuria Cbld Variant 1 71
Cobalamin D Deficiency 12
Mmahcd 71
Mahcd 53

Characteristics:

Orphanet epidemiological data:

55
methylmalonic acidemia with homocystinuria, type cbld
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: All ages;

OMIM:

53
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:

31
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 : 53 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 (MAHCC; 277400), cblD, cblF (MAHCF; 277380), and cblJ (MAHCJ; 614857). 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 methylmalonic aciduria and homocystinuria type cbld, is related to methylmalonic aciduria and homocystinuria, cblf type and methylmalonic aciduria, cblb type, and has symptoms including fatigue, seizures and lethargy. An important gene associated with Methylmalonic Aciduria and Homocystinuria, Cbld Type is MMADHC (Methylmalonic Aciduria And Homocystinuria, CblD Type). Affiliated tissues include liver, 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).

NIH Rare Diseases : 49 Methylmalonic acidemia with homocystinuria, type cblD 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 acidemia with homocystinuria, type cblD is caused by changes (mutations) in the MMADHC 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 various medications and/or supplements. Last updated: 11/9/2015

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:

# Related Disease Score Top Affiliating Genes
1 methylmalonic aciduria and homocystinuria, cblf type 11.0
2 methylmalonic aciduria, cblb type 9.9

Symptoms & Phenotypes for Methylmalonic Aciduria and Homocystinuria, Cbld Type

Symptoms via clinical synopsis from OMIM:

53
Neurologic Central Nervous System:
seizures
lethargy
dystonia
spastic ataxia
developmental delay
more
Hematology:
increased mean corpuscular volume
megaloblastic anemia

Head And Neck Eyes:
nystagmus

Laboratory Abnormalities:
methylmalonic aciduria
homocystinuria
homocystinemia
methylmalonic acidemia
decreased adenosylcobalamin (adocbl)
more

Clinical features from OMIM:

277410

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

55 31 (show all 28)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 fatigue 55 31 hallmark (90%) Very frequent (99-80%) HP:0012378
2 seizures 55 31 hallmark (90%) Very frequent (99-80%) HP:0001250
3 lethargy 55 31 hallmark (90%) Very frequent (99-80%) HP:0001254
4 intellectual disability 55 31 hallmark (90%) Very frequent (99-80%) HP:0001249
5 gait disturbance 55 31 hallmark (90%) Very frequent (99-80%) HP:0001288
6 failure to thrive 55 31 hallmark (90%) Very frequent (99-80%) HP:0001508
7 behavioral abnormality 55 31 hallmark (90%) Very frequent (99-80%) HP:0000708
8 global developmental delay 55 31 hallmark (90%) Very frequent (99-80%) HP:0001263
9 pallor 55 31 hallmark (90%) Very frequent (99-80%) HP:0000980
10 anorexia 55 31 hallmark (90%) Very frequent (99-80%) HP:0002039
11 megaloblastic bone marrow 55 31 hallmark (90%) Very frequent (99-80%) HP:0001980
12 dystonia 31 HP:0001332
13 nystagmus 31 HP:0000639
14 abnormality of movement 55 Very frequent (99-80%)
15 cerebral cortical atrophy 31 HP:0002120
16 increased mean corpuscular volume 31 HP:0005518
17 methylmalonic aciduria 31 HP:0012120
18 generalized hypotonia 31 HP:0001290
19 spastic ataxia 31 HP:0002497
20 megaloblastic anemia 31 HP:0001889
21 decreased methylcobalamin 31 HP:0003223
22 homocystinuria 31 HP:0002156
23 hyperhomocystinemia 31 HP:0002160
24 hypomethioninemia 31 HP:0003658
25 methylmalonic acidemia 31 HP:0002912
26 decreased methionine synthase activity 31 HP:0003524
27 decreased adenosylcobalamin 31 HP:0003145
28 decreased methylmalonyl-coa mutase activity 31 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:

# Genetic test Affiliating Genes
1 Homocystinuria, Cbld Type, Variant 1 28
2 Methylmalonic Acidemia with Homocystinuria Cbld 28 MMADHC
3 Methylmalonic Aciduria, Cbld Type, Variant 2 28

Anatomical Context for Methylmalonic Aciduria and Homocystinuria, Cbld Type

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

38
Liver, Bone, Bone Marrow

Publications for Methylmalonic Aciduria and Homocystinuria, Cbld Type

Articles related to Methylmalonic Aciduria and Homocystinuria, Cbld Type:

# Title Authors Year
1
Severe Neonatal Metabolic Decompensation in Methylmalonic Acidemia Caused by CblD Defect. ( 23686626 )
2013
2
Molecular mechanisms leading to three different phenotypes in the cblD defect of intracellular cobalamin metabolism. ( 22156578 )
2012
3
Gene identification for the cblD defect of vitamin B12 metabolism. ( 18385497 )
2008
4
The cblD defect causes either isolated or combined deficiency of methylcobalamin and adenosylcobalamin synthesis. ( 15292234 )
2004

Variations for Methylmalonic Aciduria and Homocystinuria, Cbld Type

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

71
# 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 14)
# 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
14 MMADHC NM_015702.2(MMADHC): c.24_25delAG (p.Arg8Serfs) deletion Pathogenic GRCh38 Chromosome 2, 149582256: 149582257

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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