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MADD
MCID: MLT118
MIFTS: 68
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Multiple Acyl-Coa Dehydrogenase Deficiency (MADD)
Categories:
Genetic diseases, Liver diseases, Metabolic diseases, Neuronal diseases, Rare diseases
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MalaCards integrated aliases for Multiple Acyl-Coa Dehydrogenase Deficiency:
Characteristics:Orphanet epidemiological data:58
multiple acyl-coa dehydrogenase deficiency
Inheritance: Autosomal recessive; Age of onset: All ages; Age of death: early childhood; HPO:31
multiple acyl-coa dehydrogenase deficiency:
Clinical modifier neonatal death Inheritance autosomal recessive inheritance Classifications:
MalaCards categories:
Global: Genetic diseases Rare diseases Metabolic diseases Anatomical: Neuronal diseases Liver diseases
ICD10:
33
Orphanet: 58
Rare neurological diseases
Inborn errors of metabolism External Ids:
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OMIM :
56
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)
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 Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.. The drugs Omeprazole and Nitric Oxide have been mentioned in the context of this disorder. Affiliated tissues include kidney, liver and brain, and related phenotypes are muscular hypotonia and elevated serum creatine kinase Disease Ontology : 12 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. Genetics Home Reference : 25 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. NIH Rare Diseases : 52 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 among affected individuals. Some have a very severe form which appears in the neonatal period and may be fatal; individuals with this form 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 mutations in the ETFA , ETFB , or ETFDH genes . Treatment varies depending on the severity and symptoms but often includes a low fat, low protein, and high carbohydrate diet. 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. Wikipedia : 74 Organic acidemia, is a term used to classify a group of metabolic disorders which disrupt normal amino... more...
GeneReviews:
NBK558236
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Human phenotypes related to Multiple Acyl-Coa Dehydrogenase Deficiency:58 31 (show top 50) (show all 77)
Symptoms via clinical synopsis from OMIM:56Clinical features from OMIM:231680GenomeRNAi Phenotypes related to Multiple Acyl-Coa Dehydrogenase Deficiency according to GeneCards Suite gene sharing:26 (show all 11)
MGI Mouse Phenotypes related to Multiple Acyl-Coa Dehydrogenase Deficiency:45
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Drugs for Multiple Acyl-Coa Dehydrogenase Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):(show all 21)
Interventional clinical trials:
Cochrane evidence based reviews: multiple acyl coenzyme a dehydrogenase deficiency |
MalaCards organs/tissues related to Multiple Acyl-Coa Dehydrogenase Deficiency:40
Kidney,
Liver,
Brain,
Heart,
Thyroid,
Skeletal Muscle,
Bone
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Articles related to Multiple Acyl-Coa Dehydrogenase Deficiency:(show top 50) (show all 462)
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Genes related to Multiple Acyl-Coa Dehydrogenase Deficiency (4 elite genes):(show all 41) - Elite gene
- Cancer Census gene in COSMIC
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ClinVar genetic disease variations for Multiple Acyl-Coa Dehydrogenase Deficiency:6 (show top 50) (show all 233)
UniProtKB/Swiss-Prot genetic disease variations for Multiple Acyl-Coa Dehydrogenase Deficiency:73 (show all 17)
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Search
GEO
for disease gene expression data for Multiple Acyl-Coa Dehydrogenase Deficiency.
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Pathways related to Multiple Acyl-Coa Dehydrogenase Deficiency according to GeneCards Suite gene sharing:(show all 12)
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Cellular components related to Multiple Acyl-Coa Dehydrogenase Deficiency according to GeneCards Suite gene sharing:
Biological processes related to Multiple Acyl-Coa Dehydrogenase Deficiency according to GeneCards Suite gene sharing:(show all 11)
Molecular functions related to Multiple Acyl-Coa Dehydrogenase Deficiency according to GeneCards Suite gene sharing:
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