CMAMMA
MCID: CMB011
MIFTS: 32

Combined Malonic and Methylmalonic Aciduria (CMAMMA)

Categories: Blood diseases, Genetic diseases, Metabolic diseases, Nephrological diseases, Neuronal diseases, Rare 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 12 53 25 59 74 37 29 13 6 72
Cmamma 57 12 53 25 59 74
Combined Malonic and Methylmalonic Acidemia 12 59
Aciduria, Combined Malonic and Methylmalonic 40

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:

Disease Ontology 12 DOID:0111263
OMIM 57 614265
KEGG 37 H02109
MeSH 44 D008052
ICD10 via Orphanet 34 E71.1
UMLS via Orphanet 73 C3280314
Orphanet 59 ORPHA289504
MedGen 42 C3280314
UMLS 72 C3280314

Summaries for Combined Malonic and Methylmalonic Aciduria

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. The signs and symptoms of CMAMMA can begin in childhood. In some children, the buildup of acids causes the blood to become too acidic (ketoacidosis), which can damage the body's tissues and organs. Other signs and symptoms may include involuntary muscle tensing (dystonia), weak muscle tone (hypotonia), developmental delay, an inability to grow and gain weight at the expected rate (failure to thrive), low blood sugar (hypoglycemia), and coma. Some affected children have an unusually small head size (microcephaly). Other people with CMAMMA do not develop signs and symptoms until adulthood. These individuals usually have neurological problems, such as seizures, loss of memory, a decline in thinking ability, or psychiatric diseases.

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

Disease Ontology : 12 An organic acidemia characterized by elevated levels of methylmalonic acid and malonic acid in body fluids typically resulting in developmental delay and failure to thrive in children and neurological symptoms in adults that has material basis in homozygous or compound heterozygous mutation in ACSF3 on 16q24.3.

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.

KEGG : 37
Combined malonic and methylmalonic aciduria (CMAMMA) is a rare recessive inborn error of metabolism characterised by elevations of urine malonic acid and methylmalonic acid. Unlike classic phenotype of methylmalonic acidemia, malonyl-CoA decarboxylase activity is normal. Mutations in ACSF3 have been identified as a cause of CMAMMA. ACSF3 encodes an enzyme that catalyzes the initial reaction in intramitochondrial fatty acid synthesis.

UniProtKB/Swiss-Prot : 74 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.

More information from OMIM: 614265

Related Diseases for Combined Malonic and Methylmalonic Aciduria

Diseases related to Combined Malonic and Methylmalonic Aciduria via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 methylmalonic acidemia 10.6
2 disorders of intracellular cobalamin metabolism 10.4
3 isolated methylmalonic acidemia 10.4
4 malonyl-coa decarboxylase deficiency 10.3
5 metabolic acidosis 10.3

Graphical network of the top 20 diseases related to Combined Malonic and Methylmalonic Aciduria:



Diseases related to Combined Malonic and Methylmalonic Aciduria

Symptoms & Phenotypes for Combined Malonic and Methylmalonic Aciduria

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

Clinical features from OMIM:

614265

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 PMID Year
1
Exome sequencing identifies ACSF3 as a cause of combined malonic and methylmalonic aciduria. 38 8 71
21841779 2011
2
Combined malonic and methylmalonic aciduria with normal malonyl-coenzyme A decarboxylase activity: a case supporting multiple aetiologies. 38 8
9700595 1998
3
Methylmalonic and malonic aciduria in a dog with progressive encephalomyelopathy. 8
8869944 1996
4
Malonic aciduria. 8
7537025 1994
5
The emerging role of the mitochondrial fatty-acid synthase (mtFASII) in the regulation of energy metabolism. 38
31376476 2019
6
Combined malonic and methylmalonic aciduria due to ACSF3 mutations: Benign clinical course in an unselected cohort. 38
30740739 2019
7
Combined malonic and methylmalonic aciduria due to ACSF3 mutations: benign clinical course in an unselected cohort. 38
29858964 2018
8
A New Approach for Fast Metabolic Diagnostics in CMAMMA. 38
26915364 2016
9
Combined malonic and methylmalonic aciduria: exome sequencing reveals mutations in the ACSF3 gene in patients with a non-classic phenotype. 38
21785126 2011

Variations for Combined Malonic and Methylmalonic Aciduria

ClinVar genetic disease variations for Combined Malonic and Methylmalonic Aciduria:

6 (show all 27)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 ACSF3 NM_174917.5(ACSF3): c.1412G> A (p.Arg471Gln) single nucleotide variant Pathogenic rs387907119 16:89211720-89211720 16:89145312-89145312
2 ACSF3 NM_174917.5(ACSF3): c.1073C> T (p.Thr358Ile) single nucleotide variant Pathogenic rs387907120 16:89180842-89180842 16:89114434-89114434
3 ACSF3 NM_174917.5(ACSF3): c.728C> T (p.Pro243Leu) single nucleotide variant Pathogenic rs140986055 16:89169073-89169073 16:89102665-89102665
4 ACSF3 NM_174917.5(ACSF3): c.593T> G (p.Met198Arg) single nucleotide variant Pathogenic rs387907121 16:89167682-89167682 16:89101274-89101274
5 ACSF3 ACSF3, LYS462THR AND GLY465_GLY470 DEL deletion Pathogenic
6 ACSF3 NM_174917.5(ACSF3): c.1567C> T (p.Arg523Ter) single nucleotide variant Pathogenic rs387907118 16:89212411-89212411 16:89146003-89146003
7 ACSF3 NM_174917.5(ACSF3): c.305del (p.Cys102fs) deletion Pathogenic 16:89167394-89167394 16:89100986-89100986
8 ACSF3 NM_174917.5(ACSF3): c.451G> T (p.Glu151Ter) single nucleotide variant Pathogenic 16:89167540-89167540 16:89101132-89101132
9 ACSF3 NM_174917.5(ACSF3): c.675del (p.Leu226fs) deletion Pathogenic 16:89169020-89169020 16:89102612-89102612
10 ACSF3 NM_174917.5(ACSF3): c.689G> A (p.Trp230Ter) single nucleotide variant Pathogenic 16:89169034-89169034 16:89102626-89102626
11 ACSF3 NM_174917.5(ACSF3): c.828G> A (p.Trp276Ter) single nucleotide variant Pathogenic 16:89178505-89178505 16:89112097-89112097
12 ACSF3 NM_174917.5(ACSF3): c.1300C> T (p.Arg434Ter) single nucleotide variant Pathogenic 16:89199604-89199604 16:89133196-89133196
13 ACSF3 NM_174917.5(ACSF3): c.1405C> T (p.Arg469Ter) single nucleotide variant Pathogenic/Likely pathogenic 16:89211713-89211713 16:89145305-89145305
14 ACSF3 NM_174917.5(ACSF3): c.1075G> A (p.Glu359Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs150487794 16:89180844-89180844 16:89114436-89114436
15 ACSF3 NM_174917.5(ACSF3): c.1672C> T (p.Arg558Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs141090143 16:89220556-89220556 16:89154148-89154148
16 ACSF3 NM_174917.5(ACSF3): c.1081G> A (p.Gly361Ser) single nucleotide variant Uncertain significance rs145285434 16:89180850-89180850 16:89114442-89114442
17 ACSF3 NM_174917.5(ACSF3): c.1411C> T (p.Arg471Trp) single nucleotide variant Uncertain significance rs138680796 16:89211719-89211719 16:89145311-89145311
18 ACSF3 NM_174917.5(ACSF3): c.541G> A (p.Glu181Lys) single nucleotide variant Uncertain significance 16:89167630-89167630 16:89101222-89101222
19 ACSF3 NM_174917.5(ACSF3): c.1406G> A (p.Arg469Gln) single nucleotide variant Uncertain significance rs144681140 16:89211714-89211714 16:89145306-89145306
20 ACSF3 NM_174917.5(ACSF3): c.122A> T (p.Asp41Val) single nucleotide variant Uncertain significance 16:89167211-89167211 16:89100803-89100803
21 ACSF3 NM_174917.5(ACSF3): c.358G> A (p.Gly120Ser) single nucleotide variant Uncertain significance 16:89167447-89167447 16:89101039-89101039
22 ACSF3 NM_174917.5(ACSF3): c.682C> G (p.His228Asp) single nucleotide variant Uncertain significance 16:89169027-89169027 16:89102619-89102619
23 ACSF3 NM_174917.5(ACSF3): c.506C> T (p.Pro169Leu) single nucleotide variant Uncertain significance 16:89167595-89167595 16:89101187-89101187
24 ACSF3 NM_174917.5(ACSF3): c.313G> A (p.Asp105Asn) single nucleotide variant Uncertain significance 16:89167402-89167402 16:89100994-89100994
25 ACSF3 NM_174917.5(ACSF3): c.431C> T (p.Ser144Phe) single nucleotide variant Uncertain significance 16:89167520-89167520 16:89101112-89101112
26 ACSF3 NM_174917.5(ACSF3): c.978-6G> A single nucleotide variant Likely benign rs377217672 16:89180741-89180741 16:89114333-89114333
27 ACSF3 NM_174917.5(ACSF3): c.854C> T (p.Pro285Leu) single nucleotide variant Benign rs143793502 16:89178531-89178531 16:89112123-89112123

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

74
# 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 rs136250421
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

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
2 Fatty acid biosynthesis hsa00061

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 MLYCD ACSF3
2 mitochondrial matrix GO:0005759 8.62 MLYCD ACSF3

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 MLYCD ACSF3
2 fatty acid metabolic process GO:0006631 8.96 MLYCD ACSF3
3 fatty acid biosynthetic process GO:0006633 8.62 MLYCD ACSF3

Sources for Combined Malonic and Methylmalonic Aciduria

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 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 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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