MADD
MCID: MLT118
MIFTS: 65

Multiple Acyl-Coa Dehydrogenase Deficiency (MADD)

Categories: Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases
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Aliases & Classifications for Multiple Acyl-Coa Dehydrogenase Deficiency

MalaCards integrated aliases for Multiple Acyl-Coa Dehydrogenase Deficiency:

Name: Multiple Acyl-Coa Dehydrogenase Deficiency 57 11 24 19 42 58 73 73 73 28 5 14
Madd 57 11 24 19 42 58 73
Ethylmalonic-Adipicaciduria 57 19 42 73
Glutaric Acidemia Iia 57 28 5 71
Glutaric Acidemia Iib 57 28 5 71
Ema 57 19 42 73
Glutaric Acidemia Type 2 11 19 58
Glutaric Acidemia Iic 57 28 5
Ga Ii 57 42 53
Multiple Acyl Coenzyme a Dehydrogenase Deficiency 43 71
Electron Transfer Flavoprotein Deficiency 11 42
Glutaric Acidemia Type Ii 19 42
Glutaric Aciduria Type 2 11 58
Glutaric Acidemia Ii 57 24
Glutaric Aciduria Ii 57 24
Glutaric Aciduria 2 19 71
Etfdh Deficiency 42 73
Etfa Deficiency 42 73
Etfb Deficiency 42 73
Mad Deficiency 11 58
Electron Transfer Flavoprotein Ubiquinone Oxidoreductase Deficiency 11
Electron Transfer Flavoprotein Dehydrogenase Deficiency 24
Multiple Fad Dehydrogenase Deficiency 42
Ethylmalonic Adipic Aciduria 75
Glutaricaciduria, Type Iia 12
Glutaric Acidemia, Type 2 42
Glutaric Aciduria, Type 2 42
Glutaric Acidemia Type 2a 5
Glutaric Acidemia Type 2c 5
Glutaric Aciduria Iia 71
Glutaric Aciduria Iib 71
Glutaric Aciduria Iic 71
Glutaric Aciduria 2a 73
Glutaricaciduria Iia 73
Glutaric Aciduria 2b 73
Glutaricaciduria Iib 73
Glutaric Aciduria 2c 73
Glutaricaciduria Iic 73
Glutaric Acidemia 2 19
Glutaricaciduria Ii 75
Gaiia 73
Gaiib 73
Gaiic 73
Ga 2 19
Ga2a 73
Ga2b 73
Ga2c 73
Ga2 57
Mad 42

Inheritance:

Autosomal recessive 58 57

Characteristics:


Age Of Onset:

All ages 58

Age Of Death:

early childhood 58

Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Multiple Acyl-Coa Dehydrogenase Deficiency

OMIM® : 57 Glutaric aciduria II (GA2) is an autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It differs from GA I (GA1; 231670) in that multiple acyl-CoA dehydrogenase deficiencies result in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids. GA II results from deficiency of any 1 of 3 molecules: the alpha (ETFA) and beta (ETFB) subunits of electron transfer flavoprotein, and electron transfer flavoprotein dehydrogenase (ETFDH). The clinical picture of GA II due to the different defects appears to be indistinguishable; each defect can lead to a range of mild or severe cases, depending presumably on the location and nature of the intragenic lesion, i.e., mutation, in each case (Goodman, 1993; Olsen et al., 2003). The heterogeneous clinical features of patients with MADD fall into 3 classes: a neonatal-onset form with congenital anomalies (type I), a neonatal-onset form without congenital anomalies (type II), and a late-onset form (type III). The neonatal-onset forms are usually fatal and are characterized by severe nonketotic hypoglycemia, metabolic acidosis, multisystem involvement, and excretion of large amounts of fatty acid- and amino acid-derived metabolites. Symptoms and age at presentation of late-onset MADD are highly variable and characterized by recurrent episodes of lethargy, vomiting, hypoglycemia, metabolic acidosis, and hepatomegaly often preceded by metabolic stress. Muscle involvement in the form of pain, weakness, and lipid storage myopathy also occurs. The organic aciduria in patients with the late-onset form of MADD is often intermittent and only evident during periods of illness or catabolic stress (summary by Frerman and Goodman, 2001). Importantly, riboflavin treatment has been shown to ameliorate the symptoms and metabolic profiles in many MADD patients, particularly those with type III, the late-onset and mildest form (Liang et al., 2009). (231680) (Updated 04-Aug-2022)

MalaCards based summary : Multiple Acyl-Coa Dehydrogenase Deficiency, also known as madd, is related to multiple acyl-coa dehydrogenase deficiency, severe neonatal type and multiple acyl-coa dehydrogenase deficiency, mild type. An important gene associated with Multiple Acyl-Coa Dehydrogenase Deficiency is ETFDH (Electron Transfer Flavoprotein Dehydrogenase), and among its related pathways/superpathways are Metabolism and Metabolism of water-soluble vitamins and cofactors. The drug Pharmaceutical Solutions has been mentioned in the context of this disorder. Affiliated tissues include liver, kidney and heart, and related phenotypes are hypoglycemia and myalgia

MedlinePlus Genetics : 42 Glutaric acidemia type II is an inherited disorder that interferes with the body's ability to break down proteins and fats to produce energy. Incompletely processed proteins and fats can build up in the body and cause the blood and tissues to become too acidic (metabolic acidosis).Glutaric acidemia type II usually appears in infancy or early childhood as a sudden episode called a metabolic crisis, in which acidosis and low blood sugar (hypoglycemia) cause weakness, behavior changes such as poor feeding and decreased activity, and vomiting. These metabolic crises, which can be life-threatening, may be triggered by common childhood illnesses or other stresses.In the most severe cases of glutaric acidemia type II, affected individuals may also be born with physical abnormalities. These may include brain malformations, an enlarged liver (hepatomegaly), a weakened and enlarged heart (dilated cardiomyopathy), fluid-filled cysts and other malformations of the kidneys, unusual facial features, and genital abnormalities. Glutaric acidemia type II may also cause a characteristic odor resembling that of sweaty feet.Some affected individuals have less severe symptoms that begin later in childhood or in adulthood. In the mildest forms of glutaric acidemia type II, muscle weakness developing in adulthood may be the first sign of the disorder.

UniProtKB/Swiss-Prot 73 Glutaric aciduria 2a : An autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It is characterized by multiple acyl-CoA dehydrogenase deficiencies resulting in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids.

Glutaric aciduria 2b : An autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It is characterized by multiple acyl-CoA dehydrogenase deficiencies resulting in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids.

Glutaric aciduria 2c : An autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It is characterized by multiple acyl-CoA dehydrogenase deficiencies resulting in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids.

GARD : 19 Glutaric acidemia type II (GA2) is a disorder that interferes with the body's ability to break down proteins and fats to produce energy. The severity of GA2 varies widely. Babies most severely affected may be born with physical abnormalities including brain malformations, an enlarged liver, kidney malformations, unusual facial features, and genital abnormalities. They may also emit an odor resembling sweaty feet. Others have a less severe form which may appear in infancy, childhood, or even adulthood. Most often, GA2 first appears in infancy or early childhood as a sudden episode of a metabolic crisis that can cause weakness, behavior changes (such as poor feeding and decreased activity) and vomiting. GA2 is inherited in an autosomal recessive manner and is caused by genetic changes in the ETFA, ETFB, or ETFDH genes.

Disease Ontology : 11 An inherited metabolic disorder characterized by the body's inability to break down proteins and fats to produce energy. It is a disorder of fatty acid, amino acid, and choline metabolism and has an autosomal recessive inheritance pattern. It has material basis in mutations in the ETFA, ETFB and ETFDH genes. It presents three clinical phenotypes: a neonatal-onset form with congenital anomalies (type I), a neonatal-onset form without congenital anomalies (type II), and a late-onset form (type III). The neonatal-onset forms are usually fatal.

Orphanet : 58 Multiple acyl-CoA dehydrogenation deficiency (MADD) is a disorder of fatty acid and amino acid oxidation and is a clinically heterogeneous disorder ranging from a severe neonatal presentation with metabolic acidosis, cardiomyopathy and liver disease, to a mild childhood/adult disease with episodic metabolic decompensation, muscle weakness, and respiratory failure.

Wikipedia : 75 Organic acidemia, is a term used to classify a group of metabolic disorders which disrupt normal amino... more...

GeneReviews: NBK558236

Related Diseases for Multiple Acyl-Coa Dehydrogenase Deficiency

Diseases related to Multiple Acyl-Coa Dehydrogenase Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 495)
# Related Disease Score Top Affiliating Genes
1 multiple acyl-coa dehydrogenase deficiency, severe neonatal type 32.7 FLAD1 ETFDH ETFB ETFA
2 multiple acyl-coa dehydrogenase deficiency, mild type 32.7 SLC25A32 FLAD1 ETFDH ETFB ETFA
3 riboflavin deficiency 32.2 SLC52A3 SLC52A2 SLC52A1 RFK FLAD1 ETFDH
4 encephalopathy, ethylmalonic 31.9 PRODH ETFA ACADS ACAD9
5 myopathy 31.6 PRODH HADHA HADH FLAD1 ETFDH CPT2
6 hypoglycemia 31.3 SLC25A20 HADHA HADH CPT2 ACADVL ACADM
7 abdominal obesity-metabolic syndrome 1 31.3 HADHA ETFDH ACADM
8 metabolic acidosis 31.2 SLC52A1 IVD ACAD9
9 reye syndrome 30.9 PRODH HADHA ETFDH CPT2 ACADVL ACADM
10 riboflavin transporter deficiency 30.8 SLC52A3 SLC52A2
11 organic acidemia 30.8 PRODH IVD GCDH ACADS ACADM
12 myoglobinuria 30.7 HADH CPT2 ACADVL
13 mitochondrial myopathy 30.5 PRODH ETFDH ACAD9
14 glutaric aciduria iii 30.5 IVD GCDH ETFA
15 propionic acidemia 30.3 IVD HADHA GCDH ETFDH CPT2 ACADVL
16 glutaric acidemia i 30.3 IVD HADHA HADH GCDH ETFDH ETFA
17 fazio-londe disease 30.3 SLC52A3 SLC52A2 SLC52A1 SLC25A32 RFK FLAD1
18 brown-vialetto-van laere syndrome 1 30.2 SLC52A3 SLC52A2
19 acyl-coa dehydrogenase, medium-chain, deficiency of 30.1 SLC25A20 HADHA HADH GCDH FLAD1 ETFDH
20 carnitine deficiency, systemic primary 30.1 SLC25A20 HADHA HADH GCDH ETFDH ETFB
21 brown-vialetto-van laere syndrome 29.8 SLC52A3 SLC52A2 SLC52A1 SLC25A32 RFK FLAD1
22 progressive bulbar palsy 29.8 SLC52A3 SLC52A2 SLC52A1 SLC25A32 FLAD1 ETFDH
23 acyl-coa dehydrogenase, very long-chain, deficiency of 29.3 SLC52A1 SLC25A20 PRODH HADHA HADH GCDH
24 transient neonatal multiple acyl-coa dehydrogenase deficiency 11.8
25 acyl-coa dehydrogenase deficiency 11.2
26 deeah syndrome 11.1
27 neurodevelopmental disorder with dysmorphic facies, impaired speech, and hypotonia 11.1
28 warburg micro syndrome 1 11.0
29 neuropathy, congenital hypomyelinating, 1, autosomal recessive 11.0
30 sandhoff disease 11.0
31 amyotrophic lateral sclerosis 1 10.9
32 frontotemporal dementia and/or amyotrophic lateral sclerosis 1 10.9
33 birt-hogg-dube syndrome 10.9
34 frontotemporal dementia 10.9
35 charcot-marie-tooth disease, type 4b2 10.9
36 spinocerebellar ataxia 8 10.9
37 ciliary dyskinesia, primary, 6 10.9
38 charcot-marie-tooth disease, type 4b3 10.9
39 frontometaphyseal dysplasia 10.9
40 charcot-marie-tooth disease 10.9
41 muscular lipidosis 10.9
42 autosomal recessive disease 10.7
43 inherited metabolic disorder 10.7
44 polymyositis 10.5
45 sensory peripheral neuropathy 10.5
46 gestational trophoblastic neoplasm 10.5
47 non-alcoholic fatty liver disease 10.4
48 leukodystrophy 10.4
49 respiratory failure 10.4
50 lipid metabolism disorder 10.4

Graphical network of the top 20 diseases related to Multiple Acyl-Coa Dehydrogenase Deficiency:



Diseases related to Multiple Acyl-Coa Dehydrogenase Deficiency

Symptoms & Phenotypes for Multiple Acyl-Coa Dehydrogenase Deficiency

Human phenotypes related to Multiple Acyl-Coa Dehydrogenase Deficiency:

58 30 (show top 50) (show all 81)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypoglycemia 58 30 Frequent (33%) Frequent (79-30%)
HP:0001943
2 myalgia 58 30 Frequent (33%) Frequent (79-30%)
HP:0003326
3 proximal muscle weakness 58 30 Frequent (33%) Frequent (79-30%)
HP:0003701
4 exercise-induced muscle fatigue 58 30 Frequent (33%) Frequent (79-30%)
HP:0009020
5 hypotonia 30 Frequent (33%) HP:0001252
6 elevated circulating creatine kinase concentration 30 Frequent (33%) HP:0003236
7 dysphagia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002015
8 hyperlordosis 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0003307
9 hepatomegaly 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002240
10 depressed nasal bridge 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0005280
11 vomiting 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002013
12 skeletal muscle atrophy 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0003202
13 congestive heart failure 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001635
14 elevated hepatic transaminase 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002910
15 dyspnea 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002094
16 areflexia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001284
17 telecanthus 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000506
18 high forehead 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000348
19 hyperammonemia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001987
20 wide anterior fontanel 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000260
21 respiratory failure 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002878
22 lactic acidosis 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0003128
23 feeding difficulties 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0011968
24 metabolic acidosis 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001942
25 decreased liver function 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001410
26 increased intramyocellular lipid droplets 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0012240
27 difficulty climbing stairs 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0003551
28 exercise intolerance 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0003546
29 decreased plasma carnitine 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0003234
30 fatigable weakness of neck muscles 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0030199
31 lacticaciduria 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0003648
32 ethylmalonic aciduria 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0003219
33 hepatic periportal necrosis 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002614
34 3-methylglutaric aciduria 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0003344
35 glutaric aciduria 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0003150
36 seizure 30 Occasional (7.5%) HP:0001250
37 abnormal pinna morphology 30 Occasional (7.5%) HP:0000377
38 increased circulating lactate dehydrogenase concentration 30 Occasional (7.5%) HP:0025435
39 elevated circulating acylcarnitine concentration 30 Occasional (7.5%) HP:0045045
40 macrocephaly 58 30 Very rare (1%) Very rare (<4-1%)
HP:0000256
41 scapular winging 58 30 Very rare (1%) Very rare (<4-1%)
HP:0003691
42 arrhythmia 58 30 Very rare (1%) Very rare (<4-1%)
HP:0011675
43 polycystic kidney dysplasia 58 30 Very rare (1%) Very rare (<4-1%)
HP:0000113
44 abnormality of the genital system 58 30 Very rare (1%) Very rare (<4-1%)
HP:0000078
45 encephalopathy 58 30 Very rare (1%) Very rare (<4-1%)
HP:0001298
46 poor head control 58 30 Very rare (1%) Very rare (<4-1%)
HP:0002421
47 cardiomyopathy 58 30 Very rare (1%) Very rare (<4-1%)
HP:0001638
48 gray matter heterotopia 58 30 Very rare (1%) Very rare (<4-1%)
HP:0002282
49 restrictive ventilatory defect 58 30 Very rare (1%) Very rare (<4-1%)
HP:0002091
50 cardiorespiratory arrest 58 30 Very rare (1%) Very rare (<4-1%)
HP:0006543

Symptoms via clinical synopsis from OMIM®:

57 (Updated 04-Aug-2022)
H E E N T:
macrocephaly
telecanthus
high forehead
flat nasal bridge
facial dysmorphism
more
G I:
hepatomegaly
vomiting
nausea
hepatic periportal necrosis
fatty infiltration of liver

Skin:
jaundice

Lab:
generalized aminoaciduria
glycosuria
ethylmalonic aciduria
glutaric acidemia
glutaric aciduria
more
Misc:
sweaty feet odor
stale breath odor
neonatal death frequent

Neuro:
muscular hypotonia
muscle weakness
hypoglycemic coma

Metabolic:
hypoglycemia
neonatal acidosis

Respiratory:
respiratory distress
pulmonary hypoplasia

G U:
renal cortical cysts
polycystic kidneys
selective proximal tubular damage
genital defects

Clinical features from OMIM®:

231680 (Updated 04-Aug-2022)

GenomeRNAi Phenotypes related to Multiple Acyl-Coa Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 no effect GR00402-S-1 10.15 ACAD9 ACADM ACADS ACADVL CPT2 ETFA
2 no effect GR00402-S-2 10.15 ACAD9 ETFA ETFDH FLAD1 GCDH HADH
3 Decreased POU5F1-GFP protein expression GR00184-A-1 9.55 ACADS CPT2 ETFDH HADHA SLC52A1
4 Increased hepcidin::fluc mRNA expression GR00253-A 8.96 HADH HADHA

MGI Mouse Phenotypes related to Multiple Acyl-Coa Dehydrogenase Deficiency:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 mortality/aging MP:0010768 9.47 ACADM ACADS ACADVL CPT2 ETFDH GCDH

Drugs & Therapeutics for Multiple Acyl-Coa Dehydrogenase Deficiency

Drugs for Multiple Acyl-Coa Dehydrogenase Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Pharmaceutical Solutions

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Fat and Sugar Metabolism During Exercise in Patients With Metabolic Myopathy Unknown status NCT02635269

Search NIH Clinical Center for Multiple Acyl-Coa Dehydrogenase Deficiency

Cochrane evidence based reviews: multiple acyl coenzyme a dehydrogenase deficiency

Genetic Tests for Multiple Acyl-Coa Dehydrogenase Deficiency

Genetic tests related to Multiple Acyl-Coa Dehydrogenase Deficiency:

# Genetic test Affiliating Genes
1 Multiple Acyl-Coa Dehydrogenase Deficiency 28 ETFA ETFB ETFDH
2 Glutaric Acidemia Iia 28
3 Glutaric Acidemia Iic 28
4 Glutaric Acidemia Iib 28

Anatomical Context for Multiple Acyl-Coa Dehydrogenase Deficiency

Organs/tissues related to Multiple Acyl-Coa Dehydrogenase Deficiency:

MalaCards : Liver, Kidney, Heart, Brain, Skeletal Muscle, Lung, Ovary
ODiseA : Respiratory System-Lung, Respiratory System, Kidney

Publications for Multiple Acyl-Coa Dehydrogenase Deficiency

Articles related to Multiple Acyl-Coa Dehydrogenase Deficiency:

(show top 50) (show all 1344)
# Title Authors PMID Year
1
Clear relationship between ETF/ETFDH genotype and phenotype in patients with multiple acyl-CoA dehydrogenation deficiency. 53 62 24 57 5
12815589 2003
2
Risk of sudden death and acute life-threatening events in patients with glutaric acidemia type II. 62 24 57 5
17977044 2008
3
Glutaric acidemia type II. Heterogeneity in beta-oxidation flux, polypeptide synthesis, and complementary DNA mutations in the alpha subunit of electron transfer flavoprotein in eight patients. 62 24 57 5
1430199 1992
4
High frequency of ETFDH c.250G>A mutation in Taiwanese patients with late-onset lipid storage myopathy. 62 57 5
20370797 2010
5
ETFDH mutations, CoQ10 levels, and respiratory chain activities in patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency. 62 57 5
19249206 2009
6
The myopathic form of coenzyme Q10 deficiency is caused by mutations in the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene. 62 57 5
17412732 2007
7
Mutations and polymorphisms of the gene encoding the beta-subunit of the electron transfer flavoprotein in three patients with glutaric acidemia type II. 62 57 5
7912128 1994
8
Molecular characterization of variant alpha-subunit of electron transfer flavoprotein in three patients with glutaric acidemia type II--and identification of glycine substitution for valine-157 in the sequence of the precursor, producing an unstable mature protein in a patient. 62 57 5
1882842 1991
9
Muscle Magnetic Resonance Imaging for the Differentiation of Multiple Acyl-CoA Dehydrogenase Deficiency and Immune-mediated Necrotizing Myopathy. 62 24 5
29336361 2018
10
Riboflavin-Responsive Multiple Acyl-CoA Dehydrogenase Deficiency Associated with Hepatoencephalomyopathy and White Matter Signal Abnormalities on Brain MRI. 62 24 5
28388738 2017
11
Riboflavin-Responsive and -Non-responsive Mutations in FAD Synthase Cause Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency. 62 24 5
27259049 2016
12
Multiple acyl-CoA dehydrogenation deficiency as decreased acyl-carnitine profile in serum. 62 24 5
25827849 2015
13
Clinical and genetical heterogeneity of late-onset multiple acyl-coenzyme A dehydrogenase deficiency. 62 24 5
25200064 2014
14
Clinical features and ETFDH mutation spectrum in a cohort of 90 Chinese patients with late-onset multiple acyl-CoA dehydrogenase deficiency. 62 24 5
24357026 2014
15
Secondary coenzyme Q10 deficiency and oxidative stress in cultured fibroblasts from patients with riboflavin responsive multiple Acyl-CoA dehydrogenation deficiency. 62 24 5
23727839 2013
16
Increased muscle coenzyme Q10 in riboflavin responsive MADD with ETFDH gene mutations due to secondary mitochondrial proliferation. 62 24 5
23628458 2013
17
Molecular analysis of 51 unrelated pedigrees with late-onset multiple acyl-CoA dehydrogenation deficiency (MADD) in southern China confirmed the most common ETFDH mutation and high carrier frequency of c.250G>A. 62 24 5
21347544 2011
18
Riboflavin-responsive lipid-storage myopathy caused by ETFDH gene mutations. 62 24 5
19758981 2010
19
Clinical and molecular investigations of Japanese cases of glutaric acidemia type 2. 62 24 5
18289905 2008
20
Electron transfer flavoprotein deficiency: functional and molecular aspects. 62 24 5
16510302 2006
21
Glutaric acidemia type II: gene structure and mutations of the electron transfer flavoprotein:ubiquinone oxidoreductase (ETF:QO) gene. 62 24 5
12359134 2002
22
Multiple acyl-CoA dehydrogenation deficiency (glutaric aciduria type II), congenital polycystic kidneys, and symmetric warty dysplasia of the cerebral cortex in two newborn brothers. II. Morphology and pathogenesis. 57 5
7173260 1982
23
Diagnosis of lethal or prenatal-onset autosomal recessive disorders by parental exome sequencing. 24 5
29096039 2018
24
Lipid-storage myopathy and respiratory insufficiency due to ETFQO mutations in a patient with late-onset multiple acyl-CoA dehydrogenation deficiency. 53 62 5
15669683 2004
25
Newly identified forms of electron transfer flavoprotein deficiency in two patients with glutaric aciduria type II. 53 62 57
2000260 1991
26
Glutaric aciduria type II: report on a previously undescribed metabolic disorder. 24 57
1245071 1976
27
Clinical, Biochemical, and Genetic Heterogeneity in Glutaric Aciduria Type II Patients. 62 5
34573316 2021
28
Hepatic Presentation of Late-Onset Multiple Acyl-CoA Dehydrogenase Deficiency (MADD): Case Report and Systematic Review. 62 5
34041209 2021
29
Mitochondrial energetic impairment in a patient with late-onset glutaric acidemia Type 2. 62 57
32804429 2020
30
Neonatal-onset multiple acyl-CoA dehydrogenase deficiency (MADD) in the ETFDH gene: A case report and a literature review. 62 5
32925727 2020
31
Late-onset riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (MADD): case reports and epidemiology of ETFDH gene mutations. 62 5
31852447 2019
32
Determinants of Riboflavin Responsiveness in Multiple Acyl-CoA Dehydrogenase Deficiency. 62 5
31331668 2019
33
Prediction of disease severity in multiple acyl-CoA dehydrogenase deficiency: A retrospective and laboratory cohort study. 62 5
31268564 2019
34
Characterization of two ETFDH mutations in a novel case of riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency. 62 5
30424791 2018
35
Novel ETFDH mutations in four cases of riboflavin responsive multiple acyl-CoA dehydrogenase deficiency. 62 5
29988809 2018
36
[A novel mutation in the ETFDH gene of an infant with multiple acyl-CoA dehydrogenase deficiency]. 62 5
30022752 2018
37
Neurite growth could be impaired by ETFDH mutation but restored by mitochondrial cofactors. 62 5
27935074 2017
38
Significant clinical heterogeneity with similar ETFDH genotype in three Chinese patients with late-onset multiple acyl-CoA dehydrogenase deficiency. 62 5
27000805 2016
39
Skeletal Muscle Magnetic Resonance Imaging of the Lower Limbs in Late-onset Lipid Storage Myopathy with Electron Transfer Flavoprotein Dehydrogenase Gene Mutations. 62 5
27270537 2016
40
Multiple acyl-CoA dehydrogenase deficiency (MADD) as a cause of late-onset treatable metabolic disease. 62 5
27038534 2016
41
Clinical, biochemical and molecular investigation of adult-onset glutaric acidemia type II: Characteristics in comparison with pediatric cases. 62 5
26403312 2016
42
Hyperprolinemia in Type 2 Glutaric Aciduria and MADD-Like Profiles. 62 5
26409463 2016
43
Riboflavin-responsive multiple Acyl-CoA dehydrogenation deficiency in 13 cases, and a literature review in mainland Chinese patients. 62 5
24522293 2014
44
Newborn Screening for Glutaric Aciduria-II: The New England Experience. 62 5
24190796 2014
45
Multi-organ abnormalities and mTORC1 activation in zebrafish model of multiple acyl-CoA dehydrogenase deficiency. 62 5
23785301 2013
46
Fatty Acid oxidation disorders in a chinese population in taiwan. 62 5
23700290 2013
47
Molecular mechanisms of riboflavin responsiveness in patients with ETF-QO variations and multiple acyl-CoA dehydrogenation deficiency. 62 5
22611163 2012
48
Adult-onset multiple acyl CoA dehydrogenation deficiency associated with an abnormal isoenzyme pattern of serum lactate dehydrogenase. 62 5
21907580 2012
49
Computational analysis of a novel mutation in ETFDH gene highlights its long-range effects on the FAD-binding motif. 62 5
22013910 2011
50
A case of late onset riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency manifesting as recurrent rhabdomyolysis and acute renal failure. 62 5
22041377 2011

Variations for Multiple Acyl-Coa Dehydrogenase Deficiency

ClinVar genetic disease variations for Multiple Acyl-Coa Dehydrogenase Deficiency:

5 (show top 50) (show all 840)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 FLAD1 NM_025207.5(FLAD1):c.836del (p.Phe279fs) DEL Pathogenic 224730 rs876661311 GRCh37: 1:154961043-154961043
GRCh38: 1:154988567-154988567
2 FLAD1 NM_025207.5(FLAD1):c.1484_1486del (p.Ser495del) DEL Pathogenic 224727 rs876661309 GRCh37: 1:154962932-154962934
GRCh38: 1:154990456-154990458
3 FLAD1 NM_025207.5(FLAD1):c.324del (p.Arg109fs) DEL Pathogenic 224733 rs876661314 GRCh37: 1:154956491-154956491
GRCh38: 1:154984015-154984015
4 FLAD1 NM_025207.5(FLAD1):c.568_569dup (p.Val191fs) DUP Pathogenic 224728 rs876661310 GRCh37: 1:154960775-154960776
GRCh38: 1:154988299-154988300
5 FLAD1 NM_025207.5(FLAD1):c.526_537delinsCA (p.Ala176fs) INDEL Pathogenic 224731 rs876661312 GRCh37: 1:154960734-154960745
GRCh38: 1:154988258-154988269
6 FLAD1 NM_025207.5(FLAD1):c.498del (p.Ser167fs) DEL Pathogenic 224734 rs876661315 GRCh37: 1:154960706-154960706
GRCh38: 1:154988230-154988230
7 FLAD1 NM_025207.5(FLAD1):c.1588C>T (p.Arg530Cys) SNV Pathogenic 224729 rs771466122 GRCh37: 1:154965222-154965222
GRCh38: 1:154992746-154992746
8 FLAD1 NM_025207.5(FLAD1):c.401_404del (p.Phe134fs) MICROSAT Pathogenic 224732 rs876661313 GRCh37: 1:154960605-154960608
GRCh38: 1:154988129-154988132
9 ETFDH NM_004453.4(ETFDH):c.1141G>C (p.Gly381Arg) SNV Pathogenic 522495 rs1466787789 GRCh37: 4:159624599-159624599
GRCh38: 4:158703447-158703447
10 ETFDH NM_004453.4(ETFDH):c.684+2T>G SNV Pathogenic 802101 rs1580406119 GRCh37: 4:159611579-159611579
GRCh38: 4:158690427-158690427
11 ETFDH NM_004453.4(ETFDH):c.1169del (p.Gly390fs) DEL Pathogenic 844449 rs1774519872 GRCh37: 4:159624626-159624626
GRCh38: 4:158703474-158703474
12 ETFB NM_001985.3(ETFB):c.253C>T (p.Arg85Ter) SNV Pathogenic 969590 rs187424345 GRCh37: 19:51856508-51856508
GRCh38: 19:51353254-51353254
13 ETFA NM_000126.4(ETFA):c.319_322del (p.His107fs) MICROSAT Pathogenic 1324349 GRCh37: 15:76584801-76584804
GRCh38: 15:76292460-76292463
14 ETFB NM_001985.3(ETFB):c.284_293del (p.Glu95fs) DEL Pathogenic 1322834 GRCh37: 19:51856468-51856477
GRCh38: 19:51353214-51353223
15 ETFDH NM_004453.4(ETFDH):c.1631dup (p.Pro545fs) DUP Pathogenic 1322835 GRCh37: 4:159627942-159627943
GRCh38: 4:158706790-158706791
16 ETFDH NM_004453.4(ETFDH):c.398_402del (p.Glu133fs) DEL Pathogenic 1322836 GRCh37: 4:159603566-159603570
GRCh38: 4:158682414-158682418
17 ETFDH NM_004453.4(ETFDH):c.1629dup (p.Ile544fs) DUP Pathogenic 1341351 GRCh37: 4:159627940-159627941
GRCh38: 4:158706788-158706789
18 ETFDH NM_004453.4(ETFDH):c.583_584dup (p.Pro196fs) MICROSAT Pathogenic 1284260 GRCh37: 4:159606345-159606346
GRCh38: 4:158685193-158685194
19 ETFA NM_000126.4(ETFA):c.*27_*30del DEL Pathogenic 1252024 GRCh37: 15:76508870-76508873
GRCh38: 15:76216529-76216532
20 ETFDH NM_004453.4(ETFDH):c.1570_1571del (p.Leu524fs) MICROSAT Pathogenic 167042 rs727503919 GRCh37: 4:159627880-159627881
GRCh38: 4:158706728-158706729
21 ETFDH NM_004453.4(ETFDH):c.56del (p.Ala18_Leu19insTer) DEL Pathogenic 1386521 GRCh37: 4:159601639-159601639
GRCh38: 4:158680487-158680487
22 ETFDH NM_004453.4(ETFDH):c.999C>A (p.Tyr333Ter) SNV Pathogenic 1403937 GRCh37: 4:159620165-159620165
GRCh38: 4:158699013-158699013
23 ETFDH NM_004453.4(ETFDH):c.1650_1651del (p.Ser551fs) DEL Pathogenic 1375348 GRCh37: 4:159627961-159627962
GRCh38: 4:158706809-158706810
24 ETFDH NM_004453.4(ETFDH):c.1512dup (p.Ile505fs) DUP Pathogenic 1376584 GRCh37: 4:159627823-159627824
GRCh38: 4:158706671-158706672
25 ETFDH NM_004453.4(ETFDH):c.1339G>T (p.Glu447Ter) SNV Pathogenic 1379360 GRCh37: 4:159627394-159627394
GRCh38: 4:158706242-158706242
26 ETFA NM_000126.4(ETFA):c.427dup (p.Thr143fs) DUP Pathogenic 1422394 GRCh37: 15:76580210-76580211
GRCh38: 15:76287869-76287870
27 ETFDH NM_004453.4(ETFDH):c.98G>A (p.Trp33Ter) SNV Pathogenic 1422520 GRCh37: 4:159601682-159601682
GRCh38: 4:158680530-158680530
28 ETFDH NM_004453.4(ETFDH):c.1011del (p.Phe337fs) DEL Pathogenic 1410339 GRCh37: 4:159620175-159620175
GRCh38: 4:158699023-158699023
29 ETFDH NM_004453.4(ETFDH):c.265C>T (p.Gln89Ter) SNV Pathogenic 1413722 GRCh37: 4:159603436-159603436
GRCh38: 4:158682284-158682284
30 ETFDH NM_004453.4(ETFDH):c.1666C>T (p.Pro556Ser) SNV Pathogenic 1417327 GRCh37: 4:159627978-159627978
GRCh38: 4:158706826-158706826
31 ETFA NM_000126.4(ETFA):c.321_322del (p.Ile108fs) MICROSAT Pathogenic 1454663 GRCh37: 15:76584801-76584802
GRCh38: 15:76292460-76292461
32 ETFB NM_001985.3(ETFB):c.490C>T (p.Arg164Trp) SNV Pathogenic 1454900 GRCh37: 19:51850261-51850261
GRCh38: 19:51347007-51347007
33 ETFDH NM_004453.4(ETFDH):c.872T>G (p.Val291Gly) SNV Pathogenic 1453914 GRCh37: 4:159618751-159618751
GRCh38: 4:158697599-158697599
34 ETFA NC_000015.9:g.(?_76508890)_(76603739_?)del DEL Pathogenic 1454539 GRCh37: 15:76508890-76603739
GRCh38:
35 ETFA NC_000015.9:g.(?_76566743)_(76603739_?)del DEL Pathogenic 1454541 GRCh37: 15:76566743-76603739
GRCh38:
36 ETFDH NM_004453.4(ETFDH):c.1699G>T (p.Glu567Ter) SNV Pathogenic 1456129 GRCh37: 4:159629524-159629524
GRCh38: 4:158708372-158708372
37 ETFDH NM_004453.4(ETFDH):c.1395T>G (p.Tyr465Ter) SNV Pathogenic 1456462 GRCh37: 4:159627450-159627450
GRCh38: 4:158706298-158706298
38 ETFB NM_001985.3(ETFB):c.426_427insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNTCTCCTGACCTCTAGATCCACCCGCCTCGGCCTCCCCAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCGACAGCTGGATTTCTT (p.Asp143delinsPhePhePhePhePhePheXaaXaaXaaXaaSerProAspLeuTer) INSERT Pathogenic 1416429 GRCh37: 19:51853594-51853595
GRCh38: 19:51350340-51350341
39 ETFA NM_000126.4(ETFA):c.44C>A (p.Ser15Ter) SNV Pathogenic 1456409 GRCh37: 15:76588074-76588074
GRCh38: 15:76295733-76295733
40 ETFDH NM_004453.4(ETFDH):c.380T>G (p.Leu127Arg) SNV Pathogenic 1456455 GRCh37: 4:159603551-159603551
GRCh38: 4:158682399-158682399
41 ETFDH NM_004453.4(ETFDH):c.344C>G (p.Ser115Ter) SNV Pathogenic 1460191 GRCh37: 4:159603515-159603515
GRCh38: 4:158682363-158682363
42 ETFDH NM_004453.4(ETFDH):c.1062del (p.Gly355fs) DEL Pathogenic 1417698 GRCh37: 4:159620227-159620227
GRCh38: 4:158699075-158699075
43 ETFDH NM_004453.4(ETFDH):c.992A>T (p.Asn331Ile) SNV Pathogenic 1416115 GRCh37: 4:159620158-159620158
GRCh38: 4:158699006-158699006
44 ETFDH NC_000004.11:g.(?_159611480)_(159620302_?)del DEL Pathogenic 1459947 GRCh37: 4:159611480-159620302
GRCh38:
45 ETFDH NM_004453.4(ETFDH):c.71dup (p.Asn24fs) DUP Pathogenic 1437786 GRCh37: 4:159601650-159601651
GRCh38: 4:158680498-158680499
46 ETFDH NM_004453.4(ETFDH):c.163_164del (p.Lys55fs) DEL Pathogenic 1457506 GRCh37: 4:159601747-159601748
GRCh38: 4:158680595-158680596
47 ETFDH NM_004453.4(ETFDH):c.269T>A (p.Leu90Ter) SNV Pathogenic 1455566 GRCh37: 4:159603440-159603440
GRCh38: 4:158682288-158682288
48 ETFDH NC_000004.11:g.(?_159593609)_(159603596_?)del DEL Pathogenic 1459946 GRCh37: 4:159593609-159603596
GRCh38:
49 ETFA NM_000126.4(ETFA):c.285del (p.Ile96fs) DEL Pathogenic 1443409 GRCh37: 15:76584838-76584838
GRCh38: 15:76292497-76292497
50 ETFA NM_000126.4(ETFA):c.693dup (p.Lys232Ter) DUP Pathogenic 1451237 GRCh37: 15:76576137-76576138
GRCh38: 15:76283796-76283797

UniProtKB/Swiss-Prot genetic disease variations for Multiple Acyl-Coa Dehydrogenase Deficiency:

73 (show all 17)
# Symbol AA change Variation ID SNP ID
1 ETFA p.Gly116Arg VAR_002366 rs119458971
2 ETFA p.Val157Gly VAR_002367 rs119458969
3 ETFA p.Thr266Met VAR_002368 rs119458970
4 ETFB p.Arg164Gln VAR_002369 rs104894677
5 ETFB p.Asp128Asn VAR_025804 rs104894678
6 ETFDH p.Ser82Phe VAR_075440 rs887871605
7 ETFDH p.Ser82Pro VAR_075441
8 ETFDH p.Ala84Thr VAR_075442 rs121964954
9 ETFDH p.His112Tyr VAR_075443
10 ETFDH p.Leu127His VAR_075444 rs121964956
11 ETFDH p.Arg175His VAR_075446 rs121964955
12 ETFDH p.Arg175Leu VAR_075447 rs121964955
13 ETFDH p.Pro456Leu VAR_075455 rs398124152
14 ETFDH p.Pro456Thr VAR_075456
15 ETFDH p.Pro562Leu VAR_075458 rs993314323
16 ETFDH p.Lys590Glu VAR_075459
17 ETFDH p.Gly611Glu VAR_075460 rs761669036

Expression for Multiple Acyl-Coa Dehydrogenase Deficiency

Search GEO for disease gene expression data for Multiple Acyl-Coa Dehydrogenase Deficiency.

Pathways for Multiple Acyl-Coa Dehydrogenase Deficiency

Pathways related to Multiple Acyl-Coa Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.08 SLC52A3 SLC52A2 SLC52A1 SLC25A32 SLC25A20 RFK
2
Show member pathways
12.52 SLC52A3 SLC52A2 SLC52A1 SLC25A32 RFK FLAD1
3
Show member pathways
12.49 SLC25A20 HADHA HADH CPT2 ACADVL ACADS
4
Show member pathways
11.58 HADHA HADH ACADVL ACADS ACADM
5
Show member pathways
11.24 HADH ACADVL ACADM
6
Show member pathways
11.16 SLC25A20 HADHA HADH GCDH CPT2 ACADVL
7 10.89 CPT2 ACADM
8 10.75 ETFA ETFDH FLAD1 RFK SLC52A1 SLC52A2
9
Show member pathways
10.74 IVD HADHA
10 9.71 RFK FLAD1

GO Terms for Multiple Acyl-Coa Dehydrogenase Deficiency

Cellular components related to Multiple Acyl-Coa Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial inner membrane GO:0005743 10.1 SLC25A32 SLC25A20 PRODH HADHA ETFDH CPT2
2 mitochondrial matrix GO:0005759 10 ACADM ACADS ACADVL ETFA ETFB ETFDH
3 mitochondrial membrane GO:0031966 9.85 SLC25A32 IVD ETFDH ACADVL ACADM ACAD9
4 mitochondrion GO:0005739 9.83 ACAD9 ACADM ACADS ACADVL CPT2 ETFA
5 electron transfer flavoprotein complex GO:0045251 9.62 ETFB ETFA

Biological processes related to Multiple Acyl-Coa Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 fatty acid beta-oxidation GO:0006635 9.96 ACADM ACADS CPT2 HADH HADHA
2 lipid metabolic process GO:0006629 9.91 IVD HADHA HADH CPT2 ACADVL ACADS
3 respiratory electron transport chain GO:0022904 9.88 ETFA ETFB ETFDH
4 electron transport chain GO:0022900 9.81 ETFDH ETFB ETFA
5 riboflavin transport GO:0032218 9.8 SLC52A3 SLC52A2 SLC52A1
6 medium-chain fatty acid metabolic process GO:0051791 9.78 ACADM ACAD9
7 cellular amino acid catabolic process GO:0009063 9.76 ETFB ETFA
8 carnitine shuttle GO:0006853 9.73 SLC25A20 CPT2
9 fatty acid metabolic process GO:0006631 9.7 IVD HADHA HADH CPT2 ACADVL ACADS
10 carnitine metabolic process GO:0009437 9.67 CPT2 ACADM
11 riboflavin metabolic process GO:0006771 9.65 SLC52A3 SLC52A2 SLC52A1 RFK FLAD1
12 fatty acid beta-oxidation using acyl-CoA dehydrogenase GO:0033539 9.53 IVD GCDH ETFDH ETFB ETFA ACADVL

Molecular functions related to Multiple Acyl-Coa Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 10.07 ACAD9 ACADM ACADS ACADVL ETFA ETFDH
2 electron transfer activity GO:0009055 9.99 ETFDH ETFB ETFA
3 fatty-acyl-CoA binding GO:0000062 9.92 HADHA GCDH ACADVL ACAD9
4 flavin adenine dinucleotide binding GO:0050660 9.86 IVD GCDH ETFDH ETFA ACADVL ACADS
5 riboflavin transmembrane transporter activity GO:0032217 9.85 SLC52A3 SLC52A2 SLC52A1
6 3-hydroxyacyl-CoA dehydrogenase activity GO:0003857 9.8 HADHA HADH
7 very-long-chain-acyl-CoA dehydrogenase activity GO:0017099 9.78 ACADVL ACAD9
8 long-chain-acyl-CoA dehydrogenase activity GO:0004466 9.76 ACADVL ACAD9
9 medium-chain-acyl-CoA dehydrogenase activity GO:0070991 9.73 ACADM ACAD9
10 butyryl-CoA dehydrogenase activity GO:0004085 9.71 ACADS IVD
11 oxidoreductase activity, acting on the CH-CH group of donors GO:0016627 9.63 IVD GCDH ACADVL ACADS ACADM ACAD9
12 acyl-CoA dehydrogenase activity GO:0003995 9.36 IVD GCDH ACADVL ACADS ACADM ACAD9

Sources for Multiple Acyl-Coa Dehydrogenase Deficiency

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 04-Aug-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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