MCID: MTH055
MIFTS: 34

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 57
Homocystinuria, Cbld Type, Variant 1 57 29 13 6
Methylmalonic Aciduria and Homocystinuria Type Cbld 12 75 15
Methylmalonic Aciduria, Cbld Type, Variant 2 57 29 6
Combined Defect in Adenosylcobalamin and Methylcobalamin Synthesis, Type Cbld 53 59
Methylmalonic Acidemia with Homocystinuria, Type Cbld 53 59
Methylmalonic Aciduria with Homocystinuria, Type Cbld 53 59
Methylmalonic Acidemia and Homocystinuria, Cbld Type 57 53
Methylmalonic Acidemia with Homocystinuria Cbld 29 6
Methylmalonic Aciduria, Cblh Type, Formerly 57 53
Methylmalonic Acidemia, Cblh Type, Formerly 57 53
Cobalamin D Defect 53 59
Cbld Defect 53 59
Vitamin B12-Responsive Methylmalonic Acidemia, Type Cbldv2 59
Vitamin B12-Responsive Methylmalonic Aciduria, Type Cbldv2 59
Methylmalonic Aciduria and Homocystinuria Cbld-Combined 75
Methylmalonic Aciduria and Homocystinuria Cbld Original 75
Methylmalonic Aciduria, Cbld Type, Variant 2, Included 53
Aciduria, Methylmalonic, and Homocystinuria, Cbld Type 40
Functional Methionine Synthase Deficiency Type Cbldv1 59
Methylmalonic Acidemia with Homocystinuria Type Cbld 53
Methylmalonic Acidemia and Homocystinuria Cbld Type 75
Mehtylmalonic Acidemia with Homocystinuria Cbi D 53
Homocystinuria, Cbld Type, Variant 1, Included 53
Methylcobalamin Deficiency Type Cbldv1 59
Methylmalonic Aciduria Cbld Variant 2 75
Homocystinuria Cbld Variant 1 75
Cobalamin D Deficiency 12
Mmahcd 75
Mahcd 57

Characteristics:

Orphanet epidemiological data:

59
methylmalonic acidemia with homocystinuria, type cbld
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: All ages;

OMIM:

57
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 : 57 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 homocystinuria, cbld type, variant 1, is related to methylmalonic aciduria and homocystinuria, cblf type and methylmalonic aciduria, cblb type. 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, and related phenotypes are intellectual disability and seizures

UniProtKB/Swiss-Prot : 75 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 : 53 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.

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:

57
Head And Neck Eyes:
nystagmus

Hematology:
increased mean corpuscular volume
megaloblastic anemia

Neurologic Central Nervous System:
seizures
dystonia
lethargy
spastic ataxia
developmental delay
more
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:

59 32 (show all 29)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 59 32 hallmark (90%) Very frequent (99-80%) HP:0001249
2 seizures 59 32 hallmark (90%) Very frequent (99-80%) HP:0001250
3 gait disturbance 59 32 hallmark (90%) Very frequent (99-80%) HP:0001288
4 failure to thrive 59 32 hallmark (90%) Very frequent (99-80%) HP:0001508
5 behavioral abnormality 59 32 hallmark (90%) Very frequent (99-80%) HP:0000708
6 global developmental delay 59 32 hallmark (90%) Very frequent (99-80%) HP:0001263
7 fatigue 59 32 hallmark (90%) Very frequent (99-80%) HP:0012378
8 pallor 59 32 hallmark (90%) Very frequent (99-80%) HP:0000980
9 anorexia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002039
10 lethargy 59 32 hallmark (90%) Very frequent (99-80%) HP:0001254
11 megaloblastic bone marrow 59 32 hallmark (90%) Very frequent (99-80%) HP:0001980
12 nystagmus 32 HP:0000639
13 muscular hypotonia 32 HP:0001252
14 abnormality of movement 59 Very frequent (99-80%)
15 dystonia 32 HP:0001332
16 cerebral cortical atrophy 32 HP:0002120
17 increased mean corpuscular volume 32 HP:0005518
18 methylmalonic aciduria 32 HP:0012120
19 generalized hypotonia 32 HP:0001290
20 spastic ataxia 32 HP:0002497
21 megaloblastic anemia 32 HP:0001889
22 decreased methylcobalamin 32 HP:0003223
23 homocystinuria 32 HP:0002156
24 hyperhomocystinemia 32 HP:0002160
25 hypomethioninemia 32 HP:0003658
26 methylmalonic acidemia 32 HP:0002912
27 decreased methionine synthase activity 32 HP:0003524
28 decreased adenosylcobalamin 32 HP:0003145
29 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:

# Genetic test Affiliating Genes
1 Homocystinuria, Cbld Type, Variant 1 29
2 Methylmalonic Acidemia with Homocystinuria Cbld 29 MMADHC
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:

41
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:

75
# 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 42)
# 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.776T> C (p.Leu259Pro) single nucleotide variant Pathogenic rs118204044 GRCh38 Chromosome 2, 149570089: 149570089
3 MMADHC NM_015702.2(MMADHC): c.545C> A (p.Thr182Asn) single nucleotide variant Pathogenic rs118204045 GRCh37 Chromosome 2, 150432289: 150432289
4 MMADHC NM_015702.2(MMADHC): c.545C> A (p.Thr182Asn) single nucleotide variant Pathogenic rs118204045 GRCh38 Chromosome 2, 149575775: 149575775
5 MMADHC NM_015702.2(MMADHC): c.746A> G (p.Tyr249Cys) single nucleotide variant Pathogenic rs118204046 GRCh37 Chromosome 2, 150426633: 150426633
6 MMADHC NM_015702.2(MMADHC): c.746A> G (p.Tyr249Cys) single nucleotide variant Pathogenic rs118204046 GRCh38 Chromosome 2, 149570119: 149570119
7 MMADHC NM_015702.2(MMADHC): c.57_64delCTCTTTAG (p.Ser20Terfs) deletion Pathogenic rs397509361 GRCh37 Chromosome 2, 150438731: 150438738
8 MMADHC NM_015702.2(MMADHC): c.57_64delCTCTTTAG (p.Ser20Terfs) deletion Pathogenic rs397509361 GRCh38 Chromosome 2, 149582217: 149582224
9 MMADHC NM_015702.2(MMADHC): c.160C> T (p.Arg54Ter) single nucleotide variant Pathogenic rs118204047 GRCh37 Chromosome 2, 150436157: 150436157
10 MMADHC NM_015702.2(MMADHC): c.160C> T (p.Arg54Ter) single nucleotide variant Pathogenic rs118204047 GRCh38 Chromosome 2, 149579643: 149579643
11 MMADHC NM_015702.2(MMADHC): c.307_324dup18 (p.Ser108_Ser109insLeuAlaGluProLeuSer) duplication Pathogenic rs397509362 GRCh37 Chromosome 2, 150435993: 150436010
12 MMADHC NM_015702.2(MMADHC): c.307_324dup18 (p.Ser108_Ser109insLeuAlaGluProLeuSer) duplication Pathogenic rs397509362 GRCh38 Chromosome 2, 149579479: 149579496
13 MMADHC NM_015702.2(MMADHC): c.748C> T (p.Arg250Ter) single nucleotide variant Pathogenic rs118204048 GRCh37 Chromosome 2, 150426631: 150426631
14 MMADHC NM_015702.2(MMADHC): c.748C> T (p.Arg250Ter) single nucleotide variant Pathogenic rs118204048 GRCh38 Chromosome 2, 149570117: 149570117
15 MMADHC NM_015702.2(MMADHC): c.419dupA (p.Tyr140Terfs) duplication Pathogenic rs397509363 GRCh37 Chromosome 2, 150433010: 150433010
16 MMADHC NM_015702.2(MMADHC): c.419dupA (p.Tyr140Terfs) duplication Pathogenic rs397509363 GRCh38 Chromosome 2, 149576496: 149576496
17 MMADHC NM_015702.2(MMADHC): c.696+3_696+6del deletion Pathogenic rs397509364 GRCh37 Chromosome 2, 150427593: 150427596
18 MMADHC NM_015702.2(MMADHC): c.696+3_696+6del deletion Pathogenic rs397509364 GRCh38 Chromosome 2, 149571079: 149571082
19 MMADHC NM_015702.2(MMADHC): c.646C> G (p.Arg216Gly) single nucleotide variant Conflicting interpretations of pathogenicity rs141093638 GRCh37 Chromosome 2, 150427649: 150427649
20 MMADHC NM_015702.2(MMADHC): c.646C> G (p.Arg216Gly) single nucleotide variant Conflicting interpretations of pathogenicity rs141093638 GRCh38 Chromosome 2, 149571135: 149571135
21 MMADHC NM_015702.2(MMADHC): c.453G> A (p.Gln151=) single nucleotide variant Benign rs11545261 GRCh38 Chromosome 2, 149576462: 149576462
22 MMADHC NM_015702.2(MMADHC): c.453G> A (p.Gln151=) single nucleotide variant Benign rs11545261 GRCh37 Chromosome 2, 150432976: 150432976
23 MMADHC NM_015702.2(MMADHC): c.455dupC (p.Cys153Metfs) duplication Pathogenic rs864309743 GRCh37 Chromosome 2, 150432974: 150432974
24 MMADHC NM_015702.2(MMADHC): c.455dupC (p.Cys153Metfs) duplication Pathogenic rs864309743 GRCh38 Chromosome 2, 149576460: 149576460
25 MMADHC NM_015702.2(MMADHC): c.228dupG (p.Asn77Glufs) duplication Pathogenic rs864309741 GRCh37 Chromosome 2, 150436089: 150436089
26 MMADHC NM_015702.2(MMADHC): c.228dupG (p.Asn77Glufs) duplication Pathogenic rs864309741 GRCh38 Chromosome 2, 149579575: 149579575
27 MMADHC NM_015702.2(MMADHC): c.133dupG (p.Ala45Glyfs) duplication Pathogenic rs864309740 GRCh37 Chromosome 2, 150438662: 150438662
28 MMADHC NM_015702.2(MMADHC): c.133dupG (p.Ala45Glyfs) duplication Pathogenic rs864309740 GRCh38 Chromosome 2, 149582148: 149582148
29 MMADHC NM_015702.2(MMADHC): c.60_61insAT (p.Leu21Ilefs) insertion Pathogenic rs864309742 GRCh38 Chromosome 2, 149582220: 149582221
30 MMADHC NM_015702.2(MMADHC): c.60_61insAT (p.Leu21Ilefs) insertion Pathogenic rs864309742 GRCh37 Chromosome 2, 150438734: 150438735
31 MMADHC NM_015702.2(MMADHC): c.578T> C (p.Val193Ala) single nucleotide variant Conflicting interpretations of pathogenicity rs147370143 GRCh37 Chromosome 2, 150432256: 150432256
32 MMADHC NM_015702.2(MMADHC): c.578T> C (p.Val193Ala) single nucleotide variant Conflicting interpretations of pathogenicity rs147370143 GRCh38 Chromosome 2, 149575742: 149575742
33 MMADHC NM_015702.2(MMADHC): c.478+6T> G single nucleotide variant Benign/Likely benign rs13402787 GRCh38 Chromosome 2, 149576431: 149576431
34 MMADHC NM_015702.2(MMADHC): c.478+6T> G single nucleotide variant Benign/Likely benign rs13402787 GRCh37 Chromosome 2, 150432945: 150432945
35 MMADHC NM_015702.2(MMADHC): c.412G> A (p.Glu138Lys) single nucleotide variant Benign/Likely benign rs61746421 GRCh38 Chromosome 2, 149576503: 149576503
36 MMADHC NM_015702.2(MMADHC): c.412G> A (p.Glu138Lys) single nucleotide variant Benign/Likely benign rs61746421 GRCh37 Chromosome 2, 150433017: 150433017
37 MMADHC NM_015702.2(MMADHC): c.428G> T (p.Ser143Ile) single nucleotide variant Benign/Likely benign rs34886916 GRCh38 Chromosome 2, 149576487: 149576487
38 MMADHC NM_015702.2(MMADHC): c.428G> T (p.Ser143Ile) single nucleotide variant Benign/Likely benign rs34886916 GRCh37 Chromosome 2, 150433001: 150433001
39 MMADHC NM_015702.2(MMADHC): c.87A> C (p.Lys29Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs61750442 GRCh38 Chromosome 2, 149582194: 149582194
40 MMADHC NM_015702.2(MMADHC): c.87A> C (p.Lys29Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs61750442 GRCh37 Chromosome 2, 150438708: 150438708
41 MMADHC NM_015702.2(MMADHC): c.24_25delAG (p.Arg8Serfs) deletion Pathogenic GRCh38 Chromosome 2, 149582256: 149582257
42 MMADHC NM_015702.2(MMADHC): c.24_25delAG (p.Arg8Serfs) deletion Pathogenic GRCh37 Chromosome 2, 150438770: 150438771

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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