Multiple acyl-CoA dehydrogenase deficiency

Georg F Hoffmann MD (Dr. Hoffmann of the University Center for Child and Adolescent Medicine in Heidelberg has no relevant financial relationships to disclose.)
Marina A Morath MD (Dr. Morath of University Children's Hospital in Heidelberg, Germany, has no relevant financial relationships to disclose.)
Tyler Reimschisel MD, editor. (Dr. Reimschisel of Vanderbilt University has received contracted research grants from Shire and Vtesse.)
Originally released May 15, 2010; last updated June 22, 2016; expires June 22, 2019

This article includes discussion of multiple acyl-CoA dehydrogenase deficiency, MADD, MAD deficiency, glutaric aciduria type II, ethylmalonic-adipic aciduria, electron transfer flavoprotein deficiency, electron transfer flavoprotein dehydrogenase deficiency, electron transfer flavoprotein: ubiquinone oxidoreductase deficiency, ETF deficiency, ETFDH deficiency, and ETFQO deficiency. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Multiple acyl-CoA dehydrogenase deficiency, also known as glutaric aciduria type II, can result in a variety of clinical manifestations. Characteristic phenotypes include the neonatal-onset (lethal) form with congenital abnormalities (type I), the neonatal-onset form with hypoketotic hypoglycemia without congenital abnormalities (type II), and the late-onset form presenting with progressive proximal myopathy (type III). The authors present an interesting and instructional case report of late-onset multiple acyl-CoA dehydrogenase deficiency showing dramatic improvement of muscular symptoms under treatment.

Key points

 

• Multiple acyl-CoA dehydrogenase deficiency, also known as glutaric aciduria type II, is a mitochondrial fatty acid oxidation disorder caused by defects of electron transfer flavoprotein (ETF) or ETF-ubiquinone oxidoreductase, or by a disturbance of riboflavin metabolism.

 

• The disease course is highly variable, ranging from severe neonatal-onset fatal disease with congenital malformations to late-onset forms in adulthood with myopathy.

 

• Multiple acyl-CoA dehydrogenase deficiency has a typical biochemical pattern of organic acids in urine and acylcarnitine profile in dried blood spots or plasma.

 

• A fat-restricted diet, the avoidance of catabolism, and supplementation with riboflavin and carnitine are the therapeutic strategies.

Historical note and terminology

Multiple acyl-CoA dehydrogenase deficiency (MADD, MIM 231680), also known as glutaric aciduria type II, is an autosomal recessive inherited disorder of fatty acid, amino acid, and choline metabolism (Frerman and Goodman 2001). Przyrembel and colleagues described the first patient in 1976 (Przyrembel et al 1976). In most cases, the disorder is due to a defect in either the alpha or beta subunit of electron transfer flavoprotein (ETFA, OMIM 608053; ETFB, OMIM 130410) or ETF dehydrogenase (ETFDH, OMIM 231675), but in some patients the disorder appears to be due to some as yet only partially identified disturbances of riboflavin metabolism (Gregersen et al 1990). Brown-Vialetto-Van Laere syndrome (OMIM 211530) and Fazio-Londe syndrome (OMIM 211500) were shown to be allelic with a riboflavin transporter defect, biochemically resulting in mild MADD (Bosch et al 2011).

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