MCID: MTH046
MIFTS: 39

Methylmalonic Acidemia Without Homocystinuria

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

Aliases & Classifications for Methylmalonic Acidemia Without Homocystinuria

MalaCards integrated aliases for Methylmalonic Acidemia Without Homocystinuria:

Name: Methylmalonic Acidemia Without Homocystinuria 20 58
Methylmalonic Aciduria Without Homocystinuria 20 58
Homocystinuria Without Methylmalonic Aciduria 58 6
Functional Methionine Synthase Deficiency 58
Methylcobalamin Deficiency 58

Characteristics:

Orphanet epidemiological data:

58
methylmalonic acidemia without homocystinuria
Inheritance: Autosomal dominant,Autosomal recessive,X-linked dominant; Prevalence: 1-9/100000 (Europe); Age of onset: All ages; Age of death: early childhood;
homocystinuria without methylmalonic aciduria
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: All ages;

Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism
Rare haematological diseases


Summaries for Methylmalonic Acidemia Without Homocystinuria

MalaCards based summary : Methylmalonic Acidemia Without Homocystinuria, also known as methylmalonic aciduria without homocystinuria, is related to homocystinuria and megaloblastic anemia. An important gene associated with Methylmalonic Acidemia Without Homocystinuria is MMADHC (Metabolism Of Cobalamin Associated D), and among its related pathways/superpathways are HIV Life Cycle and Metabolism of water-soluble vitamins and cofactors. Affiliated tissues include bone marrow and bone, and related phenotypes are failure to thrive and vomiting

Related Diseases for Methylmalonic Acidemia Without Homocystinuria

Diseases related to Methylmalonic Acidemia Without Homocystinuria via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 38)
# Related Disease Score Top Affiliating Genes
1 homocystinuria 29.7 MTRR MTR MMADHC
2 megaloblastic anemia 29.6 MTRR MTR MMADHC
3 disorders of intracellular cobalamin metabolism 29.3 MTRR MTR MMADHC
4 methylmalonic acidemia 29.3 MTRR MTR MMADHC
5 homocystinuria-megaloblastic anemia, cblg complementation type 11.4
6 homocystinuria-megaloblastic anemia, cble complementation type 11.4
7 methylmalonic aciduria and homocystinuria, cbld type 11.4
8 methylmalonic aciduria and homocystinuria, cblf type 11.1
9 yemenite deaf-blind hypopigmentation syndrome 10.0
10 microcephaly 10.0
11 pathologic nystagmus 10.0
12 cerebral atrophy 10.0
13 hypertonia 10.0
14 hypotonia 10.0
15 methylmalonic aciduria and homocystinuria type cblg 9.8 MTRR MTR
16 methylmalonic aciduria and homocystinuria type cble 9.8 MTRR MTR
17 ophthalmia neonatorum 9.8 MTRR MTR
18 methotrexate toxicity 9.8 MTRR MTR
19 urethritis 9.8 MTRR MTR
20 neural tube defects, folate-sensitive 9.8 MTRR MTR
21 myelomeningocele 9.8 MTRR MTR
22 cleft lip 9.8 MTRR MTR
23 cleft lip/palate 9.8 MTRR MTR
24 anencephaly 9.8 MTRR MTR
25 homocysteinemia 9.8 MTRR MTR
26 methylmalonic aciduria and homocystinuria, cblc type 9.7 MTR MMADHC
27 vitamin b12 deficiency 9.7 MTR MMADHC
28 physical disorder 9.7 MTRR MTR
29 organic acidemia 9.7 MTR MMADHC
30 phenylketonuria 9.7 MTRR MTR
31 migraine with aura 9.7 MTRR MTR
32 marfan syndrome 9.7 MTRR MTR
33 ventricular septal defect 9.7 MTRR MTR
34 down syndrome 9.6 MTRR MTR
35 vascular disease 9.6 MTRR MTR
36 vitamin metabolic disorder 9.5 MTRR MTR MMADHC
37 amino acid metabolic disorder 9.5 MTRR MTR MMADHC
38 male infertility 9.5 MTRR MTR

Graphical network of the top 20 diseases related to Methylmalonic Acidemia Without Homocystinuria:



Diseases related to Methylmalonic Acidemia Without Homocystinuria

Symptoms & Phenotypes for Methylmalonic Acidemia Without Homocystinuria

Human phenotypes related to Methylmalonic Acidemia Without Homocystinuria:

58 31 (show all 22)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 failure to thrive 58 31 hallmark (90%) Frequent (79-30%),Very frequent (99-80%) HP:0001508
2 vomiting 58 31 hallmark (90%) Occasional (29-5%),Very frequent (99-80%) HP:0002013
3 lethargy 58 31 hallmark (90%) Occasional (29-5%),Very frequent (99-80%) HP:0001254
4 coma 58 31 hallmark (90%) Very frequent (99-80%) HP:0001259
5 megaloblastic bone marrow 58 31 hallmark (90%) Very frequent (99-80%) HP:0001980
6 hypotonia 31 frequent (33%) HP:0001252
7 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
8 nystagmus 58 31 frequent (33%) Frequent (79-30%) HP:0000639
9 global developmental delay 58 31 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0001263
10 dehydration 58 31 frequent (33%) Frequent (79-30%) HP:0001944
11 cerebral cortical atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0002120
12 psychosis 58 31 frequent (33%) Frequent (79-30%) HP:0000709
13 respiratory distress 58 31 frequent (33%) Frequent (79-30%) HP:0002098
14 seizure 31 frequent (33%) HP:0001250
15 ataxia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001251
16 hepatomegaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0002240
17 visual impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000505
18 renal insufficiency 58 31 occasional (7.5%) Occasional (29-5%) HP:0000083
19 cerebral ischemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002637
20 dementia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000726
21 seizures 58 Frequent (79-30%)
22 muscular hypotonia 58 Very frequent (99-80%),Frequent (79-30%)

Drugs & Therapeutics for Methylmalonic Acidemia Without Homocystinuria

Search Clinical Trials , NIH Clinical Center for Methylmalonic Acidemia Without Homocystinuria

Genetic Tests for Methylmalonic Acidemia Without Homocystinuria

Anatomical Context for Methylmalonic Acidemia Without Homocystinuria

MalaCards organs/tissues related to Methylmalonic Acidemia Without Homocystinuria:

40
Bone Marrow, Bone

Publications for Methylmalonic Acidemia Without Homocystinuria

Articles related to Methylmalonic Acidemia Without Homocystinuria:

(show all 15)
# Title Authors PMID Year
1
Gene identification for the cblD defect of vitamin B12 metabolism. 6
18385497 2008
2
cblE type of homocystinuria due to methionine synthase reductase deficiency: functional correction by minigene expression. 6
15714522 2005
3
CblE type of homocystinuria due to methionine synthase reductase deficiency: clinical and molecular studies and prenatal diagnosis in two families. 6
12555939 2002
4
Hyperhomocysteinemia due to methionine synthase deficiency, cblG: structure of the MTR gene, genotype diversity, and recognition of a common mutation, P1173L. 6
12068375 2002
5
Molecular basis for methionine synthase reductase deficiency in patients belonging to the cblE complementation group of disorders in folate/cobalamin metabolism. 6
10484769 1999
6
Functionally null mutations in patients with the cblG-variant form of methionine synthase deficiency. 6
9683607 1998
7
Cloning and mapping of a cDNA for methionine synthase reductase, a flavoprotein defective in patients with homocystinuria. 6
9501215 1998
8
Human methionine synthase: cDNA cloning and identification of mutations in patients of the cblG complementation group of folate/cobalamin disorders. 6
8968737 1996
9
Defects in human methionine synthase in cblG patients. 6
8968736 1996
10
Prenatal vitamin B12 therapy of a fetus with methylcobalamin deficiency (cobalamin E disease). 6
2860337 1985
11
Homocystinuria and megaloblastic anemia responsive to vitamin B12 therapy. An inborn error of metabolism due to a defect in cobalamin metabolism. 6
6700644 1984
12
Dihydrofolate reductase deficiency causing megaloblastic anemia in two families. 6
1060915 1976
13
Homocystinuria with methylmalonic aciduria: two cases in a sibship. 6
5524089 1970
14
Spectrum of ocular manifestations in cobalamin C and cobalamin A types of methylmalonic acidemia. 61
26979128 2016
15
Prolonged exclusive breast-feeding from vegan mother causing an acute onset of isolated methylmalonic aciduria due to a mild mutase deficiency. 61
10867733 2000

Variations for Methylmalonic Acidemia Without Homocystinuria

ClinVar genetic disease variations for Methylmalonic Acidemia Without Homocystinuria:

6 (show top 50) (show all 275)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 MTRR MTRR, 4-BP DEL, NT1675 Deletion Pathogenic 7027
2 MTRR MTRR, 3-BP DEL, 1726TTG Deletion Pathogenic 7028
3 MTRR NM_002454.3(MTRR):c.1459G>A (p.Gly487Arg) SNV Pathogenic 7030 rs137853061 5:7892928-7892928 5:7892815-7892815
4 MTRR MTRR, 2-BP INS, 1623TA Insertion Pathogenic 7031
5 MTRR MTRR, 140-BP INS, NT903 Insertion Pathogenic 7032
6 MTRR NM_002454.3(MTRR):c.1361C>T (p.Ser454Leu) SNV Pathogenic 7033 rs137853062 5:7891518-7891518 5:7891405-7891405
7 MTRR NM_002454.3(MTRR):c.1379T>G (p.Leu460Ter) SNV Pathogenic 522636 rs1554006017 5:7892848-7892848 5:7892735-7892735
8 MTRR NM_002454.3(MTRR):c.1678_1681del (p.Glu560Asnfs) Microsatellite Pathogenic 631967 rs768980918 5:7896975-7896978 5:7896862-7896865
9 MTRR NC_000005.10:g.(?_7869114)_(7900078_?)del Deletion Pathogenic 831783 5:7869227-7900191
10 MTRR NC_000005.10:g.(?_7877934)_(7878332_?)del Deletion Pathogenic 833249 5:7878047-7878445
11 MTRR NM_002454.3(MTRR):c.324del (p.Lys109fs) Deletion Pathogenic 809730 rs1189298981 5:7875406-7875406 5:7875293-7875293
12 MTRR NM_002454.3(MTRR):c.230del (p.Gln77fs) Deletion Pathogenic 933492 5:7873586-7873586 5:7873473-7873473
13 MTRR NM_002454.3(MTRR):c.741del (p.Glu248fs) Deletion Pathogenic 937263 5:7878396-7878396 5:7878283-7878283
14 MTRR NM_002454.3(MTRR):c.109dup (p.Cys37fs) Duplication Pathogenic 937324 5:7871015-7871016 5:7870902-7870903
15 MTRR NM_002454.3(MTRR):c.1155_1156delinsAT (p.Arg386Ter) Indel Pathogenic 942343 5:7889216-7889217 5:7889103-7889104
16 MTRR NM_002454.3(MTRR):c.734del (p.Leu245fs) Deletion Pathogenic 953969 5:7878387-7878387 5:7878274-7878274
17 MTRR NM_002454.3(MTRR):c.1252C>T (p.Arg418Ter) SNV Pathogenic 968210 5:7889313-7889313 5:7889200-7889200
18 MMADHC NM_015702.3(MMADHC):c.748C>T (p.Arg250Ter) SNV Pathogenic 767 rs118204048 2:150426631-150426631 2:149570117-149570117
19 MMADHC NM_015702.3(MMADHC):c.419dup (p.Tyr140Ter) Duplication Pathogenic 768 rs397509363 2:150433009-150433010 2:149576495-149576496
20 MMADHC NM_015702.3(MMADHC):c.696+3_696+6del Deletion Pathogenic 769 rs397509364 2:150427593-150427596 2:149571079-149571082
21 MMADHC NM_015702.3(MMADHC):c.228dup (p.Asn77fs) Duplication Pathogenic 219000 rs864309741 2:150436088-150436089 2:149579574-149579575
22 MTRR NM_002454.3(MTRR):c.1163_1188del (p.Leu388fs) Deletion Pathogenic 962353 5:7889224-7889249 5:7889111-7889136
23 MMADHC NM_015702.3(MMADHC):c.22_23AG[1] (p.Arg8fs) Microsatellite Pathogenic 487521 rs1553454436 2:150438770-150438771 2:149582256-149582257
24 MMADHC NM_015702.3(MMADHC):c.295_296del (p.Leu99fs) Deletion Pathogenic 639047 rs1573878695 2:150436021-150436022 2:149579507-149579508
25 MTRR NM_002454.3(MTRR):c.740del (p.Pro247fs) Deletion Pathogenic 953925 5:7878391-7878391 5:7878278-7878278
26 MTRR NM_002454.3(MTRR):c.766G>T (p.Glu256Ter) SNV Pathogenic 841408 5:7878421-7878421 5:7878308-7878308
27 MTRR NM_002454.3(MTRR):c.903+469T>C SNV Pathogenic 662553 rs893229476 5:7883859-7883859 5:7883746-7883746
28 MTRR NM_002454.3(MTRR):c.270del (p.Tyr91fs) Deletion Pathogenic 650561 rs1579619636 5:7873625-7873625 5:7873512-7873512
29 MTRR NM_002454.3(MTRR):c.1183_1184del (p.Ser395fs) Deletion Pathogenic 650093 rs1579758005 5:7889244-7889245 5:7889131-7889132
30 MMADHC NC_000002.12:g.(?_149569964)_(149587107_?)del Deletion Pathogenic 831549 2:150426478-150443621
31 MMADHC NC_000002.12:g.(?_149569954)_(149587117_?)del Deletion Pathogenic 832146 2:150426468-150443631
32 MMADHC NM_015702.3(MMADHC):c.544dup (p.Thr182fs) Duplication Pathogenic 837579 2:150432289-150432290 2:149575775-149575776
33 MMADHC NM_015702.3(MMADHC):c.554_555AT[1] (p.Met186fs) Microsatellite Pathogenic 848430 2:150432277-150432278 2:149575763-149575764
34 MMADHC NM_015702.3(MMADHC):c.646C>T (p.Arg216Ter) SNV Pathogenic 960731 2:150427649-150427649 2:149571135-149571135
35 MTR MTR, IVS3AS, A-G, -166 SNV Pathogenic 14281
36 MTR NM_001291939.1(MTR):c.2044-1041_2044-1040del Microsatellite Pathogenic 14282 rs797044444 1:237024492-237024493 1:236861192-236861193
37 MTR MTR, IVS6AS, G-A, LYS203 SNV Pathogenic 14283
38 MTR NM_000254.2(MTR):c.3380dup (p.Ala1128fs) Duplication Pathogenic 14284 rs797044445 1:237057830-237057831 1:236894530-236894531
39 MTR NM_000254.2(MTR):c.1753C>T (p.Arg585Ter) SNV Pathogenic 14286 rs121913580 1:237015878-237015878 1:236852578-236852578
40 MTR NM_000254.2(MTR):c.3613G>T (p.Glu1205Ter) SNV Pathogenic 14287 rs121913581 1:237060320-237060320 1:236897020-236897020
41 MTR NM_000254.2(MTR):c.1228G>C (p.Ala410Pro) SNV Pathogenic 14288 rs121913582 1:236998886-236998886 1:236835586-236835586
42 MTR NM_000254.2(MTR):c.3518C>T (p.Pro1173Leu) SNV Pathogenic 14278 rs121913578 1:237058770-237058770 1:236895470-236895470
43 MTR NM_000254.2(MTR):c.2640_2642del (p.Ile881del) Deletion Pathogenic 14279 rs797044443 1:237044099-237044101 1:236880799-236880801
44 MTR NC_000001.11:g.(?_236795684)_(236897664_?)del Deletion Pathogenic 534574 1:236958984-237060964 1:236795684-236897664
45 MTR NM_000254.2(MTR):c.3439C>T (p.Arg1147Ter) SNV Pathogenic 650018 rs201718371 1:237058691-237058691 1:236895391-236895391
46 MTR NM_000254.2(MTR):c.2476del (p.Asp825_Ile826insTer) Deletion Pathogenic 650287 rs1572309822 1:237038028-237038028 1:236874728-236874728
47 MTRR NM_002454.3(MTRR):c.340C>T (p.Arg114Ter) SNV Pathogenic 666994 rs754990692 5:7875427-7875427 5:7875314-7875314
48 MTR NM_000254.2(MTR):c.1992_1993insATCA (p.Glu665fs) Insertion Pathogenic 648454 rs1572278166 1:237023171-237023172 1:236859871-236859872
49 MTR NM_000254.3(MTR):c.2474-1G>C SNV Pathogenic 930329 1:237038025-237038025 1:236874725-236874725
50 MTR NM_000254.3(MTR):c.610-1G>T SNV Pathogenic 931542 1:236978903-236978903 1:236815603-236815603

Expression for Methylmalonic Acidemia Without Homocystinuria

Search GEO for disease gene expression data for Methylmalonic Acidemia Without Homocystinuria.

Pathways for Methylmalonic Acidemia Without Homocystinuria

Pathways related to Methylmalonic Acidemia Without Homocystinuria according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.98 MTRR MTR MMADHC
2
Show member pathways
12.04 MTRR MTR MMADHC
3
Show member pathways
11.74 MTRR MTR
4
Show member pathways
11.52 MTRR MTR
5
Show member pathways
11.42 MTRR MTR
6
Show member pathways
11.1 MTRR MTR MMADHC
7 10.12 MTRR MTR MMADHC
8
Show member pathways
9.76 MTRR MTR

GO Terms for Methylmalonic Acidemia Without Homocystinuria

Biological processes related to Methylmalonic Acidemia Without Homocystinuria according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 methylation GO:0032259 9.32 MTRR MTR
2 cellular amino acid biosynthetic process GO:0008652 9.26 MTRR MTR
3 methionine biosynthetic process GO:0009086 9.16 MTRR MTR
4 sulfur amino acid metabolic process GO:0000096 8.96 MTRR MTR
5 cobalamin metabolic process GO:0009235 8.8 MTRR MTR MMADHC

Sources for Methylmalonic Acidemia Without Homocystinuria

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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