MCID: MTH021
MIFTS: 31

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 49 24 55 28
Methylmalonic Acidemia and Homocystinemia 49 24
Vitamin B12 Metabolic Defect with Combined Deficiency of Methylmalonyl-Coa Mutase and Homocysteine:methyltetrahydrofolate Methyltransferase 24
Vitamin B12 Metabolic Defect with Combined Deficiency of Methylmalonyl-Coa Mutase and Methionine Synthase Activities 24
Combined Defect in Adenosylcobalamin and Methylcobalamin Synthesis 55
Methylmalonic Aciduria with Homocystinuria 55
Methylmalonic Acidemia and Homocystinuria 24
Methylmalonic Aciduria and Homocystinuria 24

Characteristics:

Orphanet epidemiological data:

55
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 : 49 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.  Last updated: 10/31/2016

MalaCards based summary : Methylmalonic Acidemia with Homocystinuria, also known as methylmalonic acidemia and homocystinemia, is related to methylmalonic acidemia with homocystinuria type cblj and methylmalonic aciduria and homocystinuria, cbld type, and has symptoms including microcephaly, retinopathy and amblyopia. An important gene associated with Methylmalonic Acidemia with Homocystinuria is MMACHC (Methylmalonic Aciduria (Cobalamin Deficiency) CblC Type, With Homocystinuria). Affiliated tissues include eye, skin and heart, and related phenotype is Decreased shRNA abundance.

Genetics Home Reference : 24 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

Diseases related to Methylmalonic Acidemia with Homocystinuria via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 methylmalonic acidemia with homocystinuria type cblj 12.5
2 methylmalonic aciduria and homocystinuria, cbld type 12.1
3 methylmalonic aciduria and homocystinuria, cblf type 11.9
4 methylmalonic aciduria and homocystinuria, cblc type 11.6
5 methylmalonic acidemia and homocysteinemia, cblx type 11.4
6 methylmalonic aciduria and homocystinuria, cblj type 11.3
7 methylmalonic aciduria, cblb type 10.1
8 homocystinuria 10.1

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:

55 31 (show all 19)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 microcephaly 55 31 hallmark (90%) Very frequent (99-80%) HP:0000252
2 retinopathy 55 31 hallmark (90%) Very frequent (99-80%) HP:0000488
3 amblyopia 55 31 hallmark (90%) Very frequent (99-80%) HP:0000646
4 intellectual disability 55 31 hallmark (90%) Very frequent (99-80%) HP:0001249
5 seizures 55 31 hallmark (90%) Very frequent (99-80%) HP:0001250
6 muscular hypotonia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001252
7 lethargy 55 31 hallmark (90%) Very frequent (99-80%) HP:0001254
8 global developmental delay 55 31 hallmark (90%) Very frequent (99-80%) HP:0001263
9 failure to thrive 55 31 hallmark (90%) Very frequent (99-80%) HP:0001508
10 megaloblastic bone marrow 55 31 hallmark (90%) Very frequent (99-80%) HP:0001980
11 feeding difficulties 55 31 hallmark (90%) Very frequent (99-80%) HP:0011968
12 fatigue 55 31 hallmark (90%) Very frequent (99-80%) HP:0012378
13 hydrocephalus 55 31 frequent (33%) Frequent (79-30%) HP:0000238
14 behavioral abnormality 55 31 frequent (33%) Frequent (79-30%) HP:0000708
15 gait disturbance 55 31 frequent (33%) Frequent (79-30%) HP:0001288
16 skin rash 55 31 occasional (7.5%) Occasional (29-5%) HP:0000988
17 malformation of the heart and great vessels 55 Frequent (79-30%)
18 abnormality of movement 55 Frequent (79-30%)
19 abnormality of cardiovascular system morphology 31 frequent (33%) HP:0030680

UMLS symptoms related to Methylmalonic Acidemia with Homocystinuria:


seizures, lethargy

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

25
# 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 28 MMACHC PRDX1

Anatomical Context for Methylmalonic Acidemia with Homocystinuria

MalaCards organs/tissues related to Methylmalonic Acidemia with Homocystinuria:

38
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 all 18)
# Gene Variation Type Significance SNP ID Assembly Location
1 MMACHC NM_015506.2(MMACHC): c.609G> A (p.Trp203Ter) single nucleotide variant Pathogenic rs587776889 GRCh37 Chromosome 1, 45974647: 45974647
2 MMACHC MMACHC, 3-BP DEL, 658AAG deletion Pathogenic
3 MMACHC NM_015506.2(MMACHC): c.481C> T (p.Arg161Ter) single nucleotide variant Pathogenic rs370596113 GRCh37 Chromosome 1, 45974519: 45974519
4 MMACHC NM_015506.2(MMACHC): c.547_548delGT (p.Val183Thrfs) deletion Pathogenic rs398124293 GRCh37 Chromosome 1, 45974585: 45974586
5 MMACHC NM_015506.2(MMACHC): c.608G> A (p.Trp203Ter) single nucleotide variant Pathogenic rs398124295 GRCh37 Chromosome 1, 45974646: 45974646
6 MMACHC NM_015506.2(MMACHC): c.658_660delAAG (p.Lys220del) deletion Pathogenic rs398124296 GRCh37 Chromosome 1, 45974696: 45974698
7 MMACHC NM_015506.2(MMACHC): c.276G> T (p.Glu92Asp) single nucleotide variant Pathogenic rs556977618 GRCh37 Chromosome 1, 45973222: 45973222
8 MMACHC NM_015506.2(MMACHC): c.276G> A (p.Glu92=) single nucleotide variant Pathogenic rs556977618 GRCh37 Chromosome 1, 45973222: 45973222
9 MMACHC NM_015506.2(MMACHC): c.464G> A (p.Gly155Glu) single nucleotide variant Pathogenic rs606231425 GRCh37 Chromosome 1, 45974502: 45974502
10 MMACHC NM_015506.2(MMACHC): c.271dupA (p.Arg91Lysfs) duplication Pathogenic rs398124292 GRCh38 Chromosome 1, 45507545: 45507545
11 MMACHC NM_015506.2(MMACHC): c.347T> C (p.Leu116Pro) single nucleotide variant Pathogenic rs121918240 GRCh37 Chromosome 1, 45973954: 45973954
12 MMACHC NM_015506.2(MMACHC): c.394C> T (p.Arg132Ter) single nucleotide variant Pathogenic rs121918241 GRCh37 Chromosome 1, 45974001: 45974001
13 MMACHC NM_015506.2(MMACHC): c.331C> T (p.Arg111Ter) single nucleotide variant Pathogenic rs121918242 GRCh37 Chromosome 1, 45973938: 45973938
14 MMACHC NM_015506.2(MMACHC): c.328_331delAACC (p.Asn110Aspfs) deletion Pathogenic rs796052000 GRCh38 Chromosome 1, 45508263: 45508266
15 MMACHC NM_015506.2(MMACHC): c.440G> C (p.Gly147Ala) single nucleotide variant Pathogenic/Likely pathogenic rs140522266 GRCh37 Chromosome 1, 45974478: 45974478
16 MMACHC NM_015506.2(MMACHC): c.615C> G (p.Tyr205Ter) single nucleotide variant Pathogenic rs747527726 GRCh37 Chromosome 1, 45974653: 45974653
17 MMACHC NM_015506.2(MMACHC): c.270dupT (p.Arg91Terfs) duplication Pathogenic GRCh38 Chromosome 1, 45507544: 45507544
18 MMACHC NM_015506.2(MMACHC): c.82-11_82-8delTTCT deletion Pathogenic rs751236442 GRCh38 Chromosome 1, 45507345: 45507348

Expression for Methylmalonic Acidemia with Homocystinuria

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

Pathways for Methylmalonic Acidemia with Homocystinuria

GO Terms for Methylmalonic Acidemia with Homocystinuria

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

# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 8.62 MMACHC PRDX1

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
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
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35 IUPHAR
36 KEGG
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41 MeSH
42 MESH via Orphanet
43 MGI
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53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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