The reference OMIM entry for this protein is 231680

Multiple acyl-coa dehydrogenase deficiency; madd
Glutaric acidemia ii
Glutaric aciduria ii
Ga ii
Ethylmalonic-adipicaciduria; ema glutaric acidemia iia, included
Etfa deficiency, included
Glutaric acidemia iib, included
Etfb deficiency,

A number sign (#) is used with this entry because MADD, also known as glutaric acidemia II or glutaric aciduria II, can be caused by mutations in at least 3 different genes: ETFA (608053), ETFB (130410), and ETFDH (231675). These genes are all involved in electron transfer in the mitochondrial respiratory chain. The disorders resulting from defects in these 3 genes are referred to as glutaric acidemia IIA, IIB, and IIC, respectively, although there appears to be no difference in the clinical phenotypes.

DESCRIPTION

Glutaric aciduria II (GA II) is an autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It differs from GA I (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).

CLINICAL FEATURES

- Neonatal Onset In the son of healthy parents from the same small town in Turkey, Przyrembel et al. (1976) described fatal neonatal acidosis and hypoglycemia with a strong 'sweaty feet' odor. Large amounts of glutaric acid were found in the blood and urine. The defect was tentatively located to the metabolism of a range of acyl-CoA compounds. A possibly identically affected child died earlier. Lehnert et al. (1982), Bohm et al. (1982), and others described malformations with multiple acyl-CoA dehydrogenation deficiency: congenital polycystic kidneys, characteristic facies, etc. Typical clinical features of the disorder are respiratory distress, muscular hypotonia, sweaty feet odor, hepatomegaly, and death often in the neonatal period. Of the 12 previously reported cases reviewed by Niederwieser et al. (1983), 7 died in the first 5 days of life and only 2 patients survived to ages 5 and 19 years. Harkin et al. (1986 ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 231680 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).