MCID: MTH021
MIFTS: 34

Methylmalonic Acidemia with Homocystinuria

Categories: Rare diseases, Metabolic diseases, Blood diseases

Aliases & Classifications for Methylmalonic Acidemia with Homocystinuria

MalaCards integrated aliases for Methylmalonic Acidemia with Homocystinuria:

Name: Methylmalonic Acidemia with Homocystinuria 53 25 59 29 6
Methylmalonic Acidemia and Homocystinemia 53 25
Vitamin B12 Metabolic Defect with Combined Deficiency of Methylmalonyl-Coa Mutase and Homocysteine:methyltetrahydrofolate Methyltransferase 25
Vitamin B12 Metabolic Defect with Combined Deficiency of Methylmalonyl-Coa Mutase and Methionine Synthase Activities 25
Combined Defect in Adenosylcobalamin and Methylcobalamin Synthesis 59
Methylmalonic Aciduria with Homocystinuria 59
Methylmalonic Acidemia and Homocystinuria 25
Methylmalonic Aciduria and Homocystinuria 25

Characteristics:

Orphanet epidemiological data:

59
methylmalonic acidemia with homocystinuria
Inheritance: Autosomal recessive,X-linked recessive; Age of onset: All ages;

Classifications:



Summaries for Methylmalonic Acidemia with Homocystinuria

NIH Rare Diseases : 53 Methylmalonic acidemia with homocystinuria is an inherited disorder in which the body is unable to properly process certain nutrients from food including amino acids, lipids and cholesterol. People with this disorder have a combination of features from two separate conditions: methylmalonic acidemia and homocystinuria. When the condition begins early in life, babies have difficulty gaining weight (failure to thrive), feeding difficulties, and a pale appearance. Babies may also have weak muscle tone (hypotonia) and seizures. Most babies and children with this condition have an unusually small head size (microcephaly), intellectual disability and developmental delay. Less common features of the condition include eye problems and a blood disorder called megaloblastic anemia. When the disorder begins in adolescence or adulthood, the signs and symptoms usually include behavior and personality changes and cognitive problems (issues with learning, memory, perception etc). In some cases, abilities are lost, resulting in a decline of performance, memory and speech problems, dementia and lethargy.[12470 Methylmalonic acidemia with homocystinuria can be caused by mutations in one of several genes: MMACHC, MMADHC, LMBRD1, ABCD4, or HCFC1. Mutations in these genes account for the different types of the disorder, cblC, cblD, cblF, cblJ, and cblX, respectively. Although there is no cure for this conditions, treatment may include intramuscular injections of hydroxycobalamin, oral betaine, and folic acid. 

MalaCards based summary : Methylmalonic Acidemia with Homocystinuria, also known as methylmalonic acidemia and homocystinemia, is related to methylmalonic aciduria and homocystinuria, cblc type and methylmalonic aciduria, cblb type, and has symptoms including lethargy and seizures. An important gene associated with Methylmalonic Acidemia with Homocystinuria is MMACHC (Methylmalonic Aciduria (Cobalamin Deficiency) CblC Type, With Homocystinuria), and among its related pathways/superpathways are HIV Life Cycle and Metabolism of water-soluble vitamins and cofactors. Affiliated tissues include eye, skin and heart, and related phenotypes are microcephaly and retinopathy

Genetics Home Reference : 25 Methylmalonic acidemia with homocystinuria is an inherited disorder in which the body is unable to properly process protein building blocks (amino acids), certain fats (lipids), and a waxy fat-like substance called cholesterol. Individuals with this disorder have a combination of features from two separate conditions, methylmalonic acidemia and homocystinuria. The signs and symptoms of the combined condition, methylmalonic acidemia with homocystinuria, usually develop in infancy, although they can begin at any age.

Related Diseases for Methylmalonic Acidemia with Homocystinuria

Graphical network of the top 20 diseases related to Methylmalonic Acidemia with Homocystinuria:



Diseases related to Methylmalonic Acidemia with Homocystinuria

Symptoms & Phenotypes for Methylmalonic Acidemia with Homocystinuria

Human phenotypes related to Methylmalonic Acidemia with Homocystinuria:

59 32 (show all 19)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 microcephaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0000252
2 retinopathy 59 32 hallmark (90%) Very frequent (99-80%) HP:0000488
3 amblyopia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000646
4 intellectual disability 59 32 hallmark (90%) Very frequent (99-80%) HP:0001249
5 seizures 59 32 hallmark (90%) Very frequent (99-80%) HP:0001250
6 muscular hypotonia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001252
7 lethargy 59 32 hallmark (90%) Very frequent (99-80%) HP:0001254
8 global developmental delay 59 32 hallmark (90%) Very frequent (99-80%) HP:0001263
9 failure to thrive 59 32 hallmark (90%) Very frequent (99-80%) HP:0001508
10 megaloblastic bone marrow 59 32 hallmark (90%) Very frequent (99-80%) HP:0001980
11 feeding difficulties 59 32 hallmark (90%) Very frequent (99-80%) HP:0011968
12 fatigue 59 32 hallmark (90%) Very frequent (99-80%) HP:0012378
13 hydrocephalus 59 32 frequent (33%) Frequent (79-30%) HP:0000238
14 behavioral abnormality 59 32 frequent (33%) Frequent (79-30%) HP:0000708
15 gait disturbance 59 32 frequent (33%) Frequent (79-30%) HP:0001288
16 skin rash 59 32 occasional (7.5%) Occasional (29-5%) HP:0000988
17 malformation of the heart and great vessels 59 Frequent (79-30%)
18 abnormality of movement 59 Frequent (79-30%)
19 abnormality of cardiovascular system morphology 32 frequent (33%) HP:0030680

UMLS symptoms related to Methylmalonic Acidemia with Homocystinuria:


lethargy, seizures

GenomeRNAi Phenotypes related to Methylmalonic Acidemia with Homocystinuria according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance GR00297-A 8.62 MMACHC PRDX1

Drugs & Therapeutics for Methylmalonic Acidemia with Homocystinuria

Search Clinical Trials , NIH Clinical Center for Methylmalonic Acidemia with Homocystinuria

Genetic Tests for Methylmalonic Acidemia with Homocystinuria

Genetic tests related to Methylmalonic Acidemia with Homocystinuria:

# Genetic test Affiliating Genes
1 Methylmalonic Acidemia with Homocystinuria 29 MMACHC PRDX1

Anatomical Context for Methylmalonic Acidemia with Homocystinuria

MalaCards organs/tissues related to Methylmalonic Acidemia with Homocystinuria:

41
Eye, Skin, Heart, Bone, Bone Marrow, Kidney

Publications for Methylmalonic Acidemia with Homocystinuria

Articles related to Methylmalonic Acidemia with Homocystinuria:

# Title Authors Year
1
Methylmalonic acidemia with homocystinuria. A very rare cause of kidney failure in the neonatal period. ( 25036075 )
2014

Variations for Methylmalonic Acidemia with Homocystinuria

ClinVar genetic disease variations for Methylmalonic Acidemia with Homocystinuria:

6
(show top 50) (show all 70)
# Gene Variation Type Significance SNP ID Assembly Location
1 MMACHC NM_015506.2(MMACHC): c.271dupA (p.Arg91Lysfs) duplication Pathogenic rs398124292 GRCh38 Chromosome 1, 45507545: 45507545
2 MMACHC NM_015506.2(MMACHC): c.271dupA (p.Arg91Lysfs) duplication Pathogenic rs398124292 GRCh37 Chromosome 1, 45973217: 45973217
3 MMACHC NM_015506.2(MMACHC): c.347T> C (p.Leu116Pro) single nucleotide variant Pathogenic rs121918240 GRCh37 Chromosome 1, 45973954: 45973954
4 MMACHC NM_015506.2(MMACHC): c.347T> C (p.Leu116Pro) single nucleotide variant Pathogenic rs121918240 GRCh38 Chromosome 1, 45508282: 45508282
5 MMACHC NM_015506.2(MMACHC): c.394C> T (p.Arg132Ter) single nucleotide variant Pathogenic rs121918241 GRCh37 Chromosome 1, 45974001: 45974001
6 MMACHC NM_015506.2(MMACHC): c.394C> T (p.Arg132Ter) single nucleotide variant Pathogenic rs121918241 GRCh38 Chromosome 1, 45508329: 45508329
7 MMACHC NM_015506.2(MMACHC): c.331C> T (p.Arg111Ter) single nucleotide variant Pathogenic rs121918242 GRCh37 Chromosome 1, 45973938: 45973938
8 MMACHC NM_015506.2(MMACHC): c.331C> T (p.Arg111Ter) single nucleotide variant Pathogenic rs121918242 GRCh38 Chromosome 1, 45508266: 45508266
9 MMACHC NM_015506.2(MMACHC): c.482G> A (p.Arg161Gln) single nucleotide variant Pathogenic rs121918243 GRCh37 Chromosome 1, 45974520: 45974520
10 MMACHC NM_015506.2(MMACHC): c.482G> A (p.Arg161Gln) single nucleotide variant Pathogenic rs121918243 GRCh38 Chromosome 1, 45508848: 45508848
11 MMACHC NM_015506.2(MMACHC): c.609G> A (p.Trp203Ter) single nucleotide variant Pathogenic rs587776889 GRCh37 Chromosome 1, 45974647: 45974647
12 MMACHC NM_015506.2(MMACHC): c.609G> A (p.Trp203Ter) single nucleotide variant Pathogenic rs587776889 GRCh38 Chromosome 1, 45508975: 45508975
13 MMACHC NM_015506.2(MMACHC): c.481C> T (p.Arg161Ter) single nucleotide variant Pathogenic rs370596113 GRCh37 Chromosome 1, 45974519: 45974519
14 MMACHC NM_015506.2(MMACHC): c.481C> T (p.Arg161Ter) single nucleotide variant Pathogenic rs370596113 GRCh38 Chromosome 1, 45508847: 45508847
15 MMACHC NM_015506.2(MMACHC): c.547_548delGT (p.Val183Thrfs) deletion Pathogenic rs398124293 GRCh37 Chromosome 1, 45974585: 45974586
16 MMACHC NM_015506.2(MMACHC): c.547_548delGT (p.Val183Thrfs) deletion Pathogenic rs398124293 GRCh38 Chromosome 1, 45508913: 45508914
17 MMACHC NM_015506.2(MMACHC): c.608G> A (p.Trp203Ter) single nucleotide variant Pathogenic rs398124295 GRCh37 Chromosome 1, 45974646: 45974646
18 MMACHC NM_015506.2(MMACHC): c.608G> A (p.Trp203Ter) single nucleotide variant Pathogenic rs398124295 GRCh38 Chromosome 1, 45508974: 45508974
19 MMACHC NM_015506.2(MMACHC): c.658_660delAAG (p.Lys220del) deletion Pathogenic rs398124296 GRCh37 Chromosome 1, 45974696: 45974698
20 MMACHC NM_015506.2(MMACHC): c.658_660delAAG (p.Lys220del) deletion Pathogenic rs398124296 GRCh38 Chromosome 1, 45509024: 45509026
21 MMACHC NM_015506.2(MMACHC): c.276G> T (p.Glu92Asp) single nucleotide variant Pathogenic rs556977618 GRCh37 Chromosome 1, 45973222: 45973222
22 MMACHC NM_015506.2(MMACHC): c.276G> T (p.Glu92Asp) single nucleotide variant Pathogenic rs556977618 GRCh38 Chromosome 1, 45507550: 45507550
23 MMACHC NM_015506.2(MMACHC): c.276G> A (p.Glu92=) single nucleotide variant Pathogenic rs556977618 GRCh37 Chromosome 1, 45973222: 45973222
24 MMACHC NM_015506.2(MMACHC): c.276G> A (p.Glu92=) single nucleotide variant Pathogenic rs556977618 GRCh38 Chromosome 1, 45507550: 45507550
25 MMACHC NM_015506.2(MMACHC): c.464G> A (p.Gly155Glu) single nucleotide variant Pathogenic rs606231425 GRCh37 Chromosome 1, 45974502: 45974502
26 MMACHC NM_015506.2(MMACHC): c.464G> A (p.Gly155Glu) single nucleotide variant Pathogenic rs606231425 GRCh38 Chromosome 1, 45508830: 45508830
27 MMACHC NM_015506.2(MMACHC): c.848G> T (p.Ter283Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs201025783 GRCh37 Chromosome 1, 45974886: 45974886
28 MMACHC NM_015506.2(MMACHC): c.848G> T (p.Ter283Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs201025783 GRCh38 Chromosome 1, 45509214: 45509214
29 MMACHC NM_015506.2(MMACHC): c.181C> T (p.Arg61Trp) single nucleotide variant Uncertain significance rs200483477 GRCh38 Chromosome 1, 45507455: 45507455
30 MMACHC NM_015506.2(MMACHC): c.181C> T (p.Arg61Trp) single nucleotide variant Uncertain significance rs200483477 GRCh37 Chromosome 1, 45973127: 45973127
31 MMACHC NM_015506.2(MMACHC): c.316G> A (p.Glu106Lys) single nucleotide variant Uncertain significance rs201617713 GRCh38 Chromosome 1, 45508251: 45508251
32 MMACHC NM_015506.2(MMACHC): c.316G> A (p.Glu106Lys) single nucleotide variant Uncertain significance rs201617713 GRCh37 Chromosome 1, 45973923: 45973923
33 MMACHC NM_015506.2(MMACHC): c.328_331delAACC (p.Asn110Aspfs) deletion Pathogenic rs796052000 GRCh38 Chromosome 1, 45508263: 45508266
34 MMACHC NM_015506.2(MMACHC): c.328_331delAACC (p.Asn110Aspfs) deletion Pathogenic rs796052000 GRCh37 Chromosome 1, 45973935: 45973938
35 MMACHC NM_015506.2(MMACHC): c.388_390delTAC (p.Tyr130del) deletion Pathogenic/Likely pathogenic rs796051998 GRCh37 Chromosome 1, 45973995: 45973997
36 MMACHC NM_015506.2(MMACHC): c.388_390delTAC (p.Tyr130del) deletion Pathogenic/Likely pathogenic rs796051998 GRCh38 Chromosome 1, 45508323: 45508325
37 MMACHC NM_015506.2(MMACHC): c.420G> A (p.Trp140Ter) single nucleotide variant not provided rs796051996 GRCh37 Chromosome 1, 45974027: 45974027
38 MMACHC NM_015506.2(MMACHC): c.420G> A (p.Trp140Ter) single nucleotide variant not provided rs796051996 GRCh38 Chromosome 1, 45508355: 45508355
39 MMACHC NM_015506.2(MMACHC): c.440G> A (p.Gly147Asp) single nucleotide variant Pathogenic rs140522266 GRCh37 Chromosome 1, 45974478: 45974478
40 MMACHC NM_015506.2(MMACHC): c.440G> A (p.Gly147Asp) single nucleotide variant Pathogenic rs140522266 GRCh38 Chromosome 1, 45508806: 45508806
41 MMACHC NM_015506.2(MMACHC): c.440G> C (p.Gly147Ala) single nucleotide variant Pathogenic/Likely pathogenic rs140522266 GRCh38 Chromosome 1, 45508806: 45508806
42 MMACHC NM_015506.2(MMACHC): c.440G> C (p.Gly147Ala) single nucleotide variant Pathogenic/Likely pathogenic rs140522266 GRCh37 Chromosome 1, 45974478: 45974478
43 MMACHC NM_015506.2(MMACHC): c.616C> T (p.Arg206Trp) single nucleotide variant Uncertain significance rs538023671 GRCh38 Chromosome 1, 45508982: 45508982
44 MMACHC NM_015506.2(MMACHC): c.616C> T (p.Arg206Trp) single nucleotide variant Uncertain significance rs538023671 GRCh37 Chromosome 1, 45974654: 45974654
45 MMACHC NM_015506.2(MMACHC): c.766_771delGCCCCC (p.Ala256_Pro257del) deletion Uncertain significance rs796064513 GRCh37 Chromosome 1, 45974804: 45974809
46 MMACHC NM_015506.2(MMACHC): c.766_771delGCCCCC (p.Ala256_Pro257del) deletion Uncertain significance rs796064513 GRCh38 Chromosome 1, 45509132: 45509137
47 MMACHC NM_015506.2(MMACHC): c.615C> G (p.Tyr205Ter) single nucleotide variant Pathogenic rs747527726 GRCh37 Chromosome 1, 45974653: 45974653
48 MMACHC NM_015506.2(MMACHC): c.615C> G (p.Tyr205Ter) single nucleotide variant Pathogenic rs747527726 GRCh38 Chromosome 1, 45508981: 45508981
49 MMACHC NM_015506.2(MMACHC): c.389A> G (p.Tyr130Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs200094982 GRCh38 Chromosome 1, 45508324: 45508324
50 MMACHC NM_015506.2(MMACHC): c.389A> G (p.Tyr130Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs200094982 GRCh37 Chromosome 1, 45973996: 45973996

Expression for Methylmalonic Acidemia with Homocystinuria

Search GEO for disease gene expression data for Methylmalonic Acidemia with Homocystinuria.

Pathways for Methylmalonic Acidemia with Homocystinuria

Pathways related to Methylmalonic Acidemia with Homocystinuria according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.8 MMACHC MMADHC PRDX1
2
Show member pathways
11.76 MMACHC MMADHC
3
Show member pathways
10.92 MMACHC MMADHC
4 9.95 MMACHC MMADHC

GO Terms for Methylmalonic Acidemia with Homocystinuria

Cellular components related to Methylmalonic Acidemia with Homocystinuria according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 8.8 MMACHC MMADHC PRDX1

Biological processes related to Methylmalonic Acidemia with Homocystinuria according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cobalamin metabolic process GO:0009235 8.62 MMACHC MMADHC

Molecular functions related to Methylmalonic Acidemia with Homocystinuria according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 8.62 MMACHC PRDX1

Sources for Methylmalonic Acidemia with Homocystinuria

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
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36 IUPHAR
37 KEGG
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44 MeSH
45 MESH via Orphanet
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58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
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74 UMLS via Orphanet
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