MCID: CMB011
MIFTS: 26

Combined Malonic and Methylmalonic Aciduria

Categories: Genetic diseases, Rare diseases, Metabolic diseases

Aliases & Classifications for Combined Malonic and Methylmalonic Aciduria

MalaCards integrated aliases for Combined Malonic and Methylmalonic Aciduria:

Name: Combined Malonic and Methylmalonic Aciduria 57 53 25 59 75 37 29 13 6 73
Cmamma 57 53 25 59 75
Aciduria, Combined Malonic and Methylmalonic 40
Combined Malonic and Methylmalonic Acidemia 59

Characteristics:

Orphanet epidemiological data:

59
combined malonic and methylmalonic acidemia
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: All ages;

HPO:

32
combined malonic and methylmalonic aciduria:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Inborn errors of metabolism


External Ids:

OMIM 57 614265
Orphanet 59 ORPHA289504
ICD10 via Orphanet 34 E71.1
UMLS via Orphanet 74 C3280314
MedGen 42 C3280314
MeSH 44 D008052
KEGG 37 H02109
UMLS 73 C3280314

Summaries for Combined Malonic and Methylmalonic Aciduria

NIH Rare Diseases : 53 Combined malonic and methylmalonic aciduria (CMAMMA) is an inherited condition in which certain chemicals accumulate in the blood and urine of affected individuals. People with CMAMMA can have a wide variety of symptoms. Children with CMAMMA can suffer from developmental delays and a failure to gain weight and grow (failure to thrive). In those who were identified as adults, symptoms may include psychiatric features and neurological problems that can mimic Alzheimer's disease and multiple sclerosis. Recently, researchers have found that mutations in the ACSF3 gene cause CMAMMA.

MalaCards based summary : Combined Malonic and Methylmalonic Aciduria, is also known as cmamma. An important gene associated with Combined Malonic and Methylmalonic Aciduria is ACSF3 (Acyl-CoA Synthetase Family Member 3), and among its related pathways/superpathways is Valine, leucine and isoleucine degradation. Related phenotypes are failure to thrive and global developmental delay

Genetics Home Reference : 25 Combined malonic and methylmalonic aciduria (CMAMMA) is a condition characterized by high levels of certain chemicals, known as malonic acid and methylmalonic acid, in the body. A distinguishing feature of this condition is higher levels of methylmalonic acid than malonic acid in the urine, although both are elevated.

UniProtKB/Swiss-Prot : 75 Combined malonic and methylmalonic aciduria: A metabolic disease characterized by malonic and methylmalonic aciduria, with urinary excretion of much larger amounts of methylmalonic acid than malonic acid, in the presence of normal malonyl-CoA decarboxylase activity. Clinical features include coma, ketoacidosis, hypoglycemia, failure to thrive, microcephaly, dystonia, axial hypotonia and/or developmental delay, and neurologic manifestations including seizures, psychiatric disease and/or cognitive decline.

Description from OMIM: 614265

Related Diseases for Combined Malonic and Methylmalonic Aciduria

Symptoms & Phenotypes for Combined Malonic and Methylmalonic Aciduria

Clinical features from OMIM:

614265

Human phenotypes related to Combined Malonic and Methylmalonic Aciduria:

32 (show all 8)
# Description HPO Frequency HPO Source Accession
1 failure to thrive 32 HP:0001508
2 global developmental delay 32 HP:0001263
3 dehydration 32 HP:0001944
4 vomiting 32 HP:0002013
5 diarrhea 32 HP:0002014
6 methylmalonic aciduria 32 HP:0012120
7 ketoacidosis 32 HP:0001993
8 generalized clonic seizures 32 HP:0011169

Drugs & Therapeutics for Combined Malonic and Methylmalonic Aciduria

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Combined Malonic and Methylmalonic Aciduria (CMAMMA): Gene Identification and Outcome Study Unknown status NCT01289158

Search NIH Clinical Center for Combined Malonic and Methylmalonic Aciduria

Genetic Tests for Combined Malonic and Methylmalonic Aciduria

Genetic tests related to Combined Malonic and Methylmalonic Aciduria:

# Genetic test Affiliating Genes
1 Combined Malonic and Methylmalonic Aciduria 29 ACSF3

Anatomical Context for Combined Malonic and Methylmalonic Aciduria

Publications for Combined Malonic and Methylmalonic Aciduria

Articles related to Combined Malonic and Methylmalonic Aciduria:

# Title Authors Year
1
Combined malonic and methylmalonic aciduria due to ACSF3 mutations: benign clinical course in an unselected cohort. ( 29858964 )
2018
2
Exome sequencing identifies ACSF3 as a cause of combined malonic and methylmalonic aciduria. ( 21841779 )
2011
3
Combined malonic and methylmalonic aciduria: exome sequencing reveals mutations in the ACSF3 gene in patients with a non-classic phenotype. ( 21785126 )
2011
4
Combined malonic and methylmalonic aciduria with normal malonyl-coenzyme A decarboxylase activity: a case supporting multiple aetiologies. ( 9700595 )
1998

Variations for Combined Malonic and Methylmalonic Aciduria

UniProtKB/Swiss-Prot genetic disease variations for Combined Malonic and Methylmalonic Aciduria:

75
# Symbol AA change Variation ID SNP ID
1 ACSF3 p.Met198Arg VAR_066504 rs387907121
2 ACSF3 p.Pro243Leu VAR_066505 rs140986055
3 ACSF3 p.Thr358Ile VAR_066506 rs387907120
4 ACSF3 p.Glu359Lys VAR_066507 rs150487794
5 ACSF3 p.Lys462Thr VAR_066508
6 ACSF3 p.Arg471Gln VAR_066510 rs387907119
7 ACSF3 p.Arg471Trp VAR_066511 rs138680796
8 ACSF3 p.Gly480Ser VAR_066512
9 ACSF3 p.Arg558Trp VAR_066513 rs141090143

ClinVar genetic disease variations for Combined Malonic and Methylmalonic Aciduria:

6
(show all 21)
# Gene Variation Type Significance SNP ID Assembly Location
1 ACSF3 NM_174917.4(ACSF3): c.1672C> T (p.Arg558Trp) single nucleotide variant Pathogenic/Likely pathogenic rs141090143 GRCh37 Chromosome 16, 89220556: 89220556
2 ACSF3 NM_174917.4(ACSF3): c.1672C> T (p.Arg558Trp) single nucleotide variant Pathogenic/Likely pathogenic rs141090143 GRCh38 Chromosome 16, 89154148: 89154148
3 ACSF3 NM_174917.4(ACSF3): c.1567C> T (p.Arg523Ter) single nucleotide variant Pathogenic rs387907118 GRCh37 Chromosome 16, 89212411: 89212411
4 ACSF3 NM_174917.4(ACSF3): c.1567C> T (p.Arg523Ter) single nucleotide variant Pathogenic rs387907118 GRCh38 Chromosome 16, 89146003: 89146003
5 ACSF3 NM_174917.4(ACSF3): c.1411C> T (p.Arg471Trp) single nucleotide variant Pathogenic rs138680796 GRCh37 Chromosome 16, 89211719: 89211719
6 ACSF3 NM_174917.4(ACSF3): c.1411C> T (p.Arg471Trp) single nucleotide variant Pathogenic rs138680796 GRCh38 Chromosome 16, 89145311: 89145311
7 ACSF3 NM_174917.4(ACSF3): c.1412G> A (p.Arg471Gln) single nucleotide variant Pathogenic rs387907119 GRCh37 Chromosome 16, 89211720: 89211720
8 ACSF3 NM_174917.4(ACSF3): c.1412G> A (p.Arg471Gln) single nucleotide variant Pathogenic rs387907119 GRCh38 Chromosome 16, 89145312: 89145312
9 ACSF3 NM_174917.4(ACSF3): c.1073C> T (p.Thr358Ile) single nucleotide variant Pathogenic rs387907120 GRCh37 Chromosome 16, 89180842: 89180842
10 ACSF3 NM_174917.4(ACSF3): c.1073C> T (p.Thr358Ile) single nucleotide variant Pathogenic rs387907120 GRCh38 Chromosome 16, 89114434: 89114434
11 ACSF3 NM_174917.4(ACSF3): c.728C> T (p.Pro243Leu) single nucleotide variant Pathogenic rs140986055 GRCh37 Chromosome 16, 89169073: 89169073
12 ACSF3 NM_174917.4(ACSF3): c.728C> T (p.Pro243Leu) single nucleotide variant Pathogenic rs140986055 GRCh38 Chromosome 16, 89102665: 89102665
13 ACSF3 NM_174917.4(ACSF3): c.593T> G (p.Met198Arg) single nucleotide variant Pathogenic rs387907121 GRCh37 Chromosome 16, 89167682: 89167682
14 ACSF3 NM_174917.4(ACSF3): c.593T> G (p.Met198Arg) single nucleotide variant Pathogenic rs387907121 GRCh38 Chromosome 16, 89101274: 89101274
15 ACSF3 ACSF3, LYS462THR AND GLY465_GLY470 DEL deletion Pathogenic
16 ACSF3 NM_174917.4(ACSF3): c.854C> T (p.Pro285Leu) single nucleotide variant Benign rs143793502 GRCh37 Chromosome 16, 89178531: 89178531
17 ACSF3 NM_174917.4(ACSF3): c.854C> T (p.Pro285Leu) single nucleotide variant Benign rs143793502 GRCh38 Chromosome 16, 89112123: 89112123
18 ACSF3 NM_174917.4(ACSF3): c.978-6G> A single nucleotide variant Likely benign rs377217672 GRCh37 Chromosome 16, 89180741: 89180741
19 ACSF3 NM_174917.4(ACSF3): c.978-6G> A single nucleotide variant Likely benign rs377217672 GRCh38 Chromosome 16, 89114333: 89114333
20 ACSF3 NM_174917.4(ACSF3): c.1081G> A (p.Gly361Ser) single nucleotide variant Uncertain significance rs145285434 GRCh38 Chromosome 16, 89114442: 89114442
21 ACSF3 NM_174917.4(ACSF3): c.1081G> A (p.Gly361Ser) single nucleotide variant Uncertain significance rs145285434 GRCh37 Chromosome 16, 89180850: 89180850

Expression for Combined Malonic and Methylmalonic Aciduria

Search GEO for disease gene expression data for Combined Malonic and Methylmalonic Aciduria.

Pathways for Combined Malonic and Methylmalonic Aciduria

Pathways related to Combined Malonic and Methylmalonic Aciduria according to KEGG:

37
# Name Kegg Source Accession
1 Valine, leucine and isoleucine degradation hsa00280

GO Terms for Combined Malonic and Methylmalonic Aciduria

Cellular components related to Combined Malonic and Methylmalonic Aciduria according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 8.96 ACSF3 MLYCD
2 mitochondrial matrix GO:0005759 8.62 ACSF3 MLYCD

Biological processes related to Combined Malonic and Methylmalonic Aciduria according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.16 ACSF3 MLYCD
2 fatty acid metabolic process GO:0006631 8.96 ACSF3 MLYCD
3 fatty acid biosynthetic process GO:0006633 8.62 ACSF3 MLYCD

Sources for Combined Malonic and Methylmalonic Aciduria

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
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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