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  • Updated 03.22.2020
  • Released 05.15.2010
  • Expires For CME 03.22.2023

Multiple acyl-CoA dehydrogenase deficiency

Introduction

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 novel insights in pathophysiology and genetics of Multiple acyl-CoA dehydrogenase deficiency.

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 disturbance of riboflavin metabolism.

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

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

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

• Acylcarnitine profiling should always be included in the diagnostic work-up of infantile lactic acidemia.

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 (25). Przyrembel and colleagues described the first patient in 1976 (68). 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. 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 (08).

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