C6—C10-Dicarboxylic Aciduria: Investigations of a Patient with Riboflavin Responsive Multiple Acyl-CoA Dehydrogenation Defects

Abstract

SummaryThe abnormal metabolites-adipic, suberic, and sebacic acidswere detected in large amounts in the urine of a boy during a Reye's syndrome-like crisis. Substantial amounts of 5-OH-caproic acid, caproylglycine, glutaric acid, and 3-OH-butyric acid and moderately elevated amounts of ethylmalonic acid, methylsuccinic acid, 3-OH-isovaleric acid, and isovalerylglycine were also found. These metabolites were consistently present in urine samples collected in the boy's habitual condition after the attack.

Multiple Acyl-Coenzyme A Dehydrogenation Disorder Responsive to Riboflavin: Substrate Oxidation, Flavin Metabolism, and Flavoenzyme Activities in Fibroblasts

“…Thus, control mitochondrial FAD contents apparently attain steady state at even very low extracellular riboflavin concentrations (4.4 crg/L = 12 nM), whereas the patient's cells require much higher extracellular concentrations to reach control FAD levels. These observations are consistent with the vitamin responsiveness of his metabolic block (4,11). Inasmuch as we found normal whole cell and cytosolic I4C-FMN and -FAD contents in the patient, this result suggests defective maintenance of mitochondrial FMN and FAD levels in his cells.…”

“…The first patient with this variant was described by Gregersen ct 01. (4) ["C(U)]palmitate at 50% of control levels (4). fibroblast ADH activities.…”

On the Biologic Origin of C6-C10-Dicarboxylic and C6-C10-ω-1-Hydroxy Monocarboxylic Acids in Human and Rat with Acyl-CoA Dehydrogenation Deficiencies: in Vitro Studies on the ω- and ω-1-Oxidation of Medium-Chain (C6-C12) Fatty Acids in Human and Rat Liver

“…The apparent Km of 4-1 86 pmole/liter for dodecanoic acid may also be important in humans when the liberation of fatty acids from the fat deposits is excessive, i.e., ketosis and in patients with acyl-CoA dehydrogenation deficiencies, where medium-chain fatty acids have been indicated to be accumulated (6,8,10,11,12,13,15,25,30,31,36,37).…”

“…It is argued that 5-hydroxy hexanoic, 7-hydroxy octanoic, and 9-hydroxy decanoic acids found in some patients with acyl-CoA dehydrogenation deficiencies are produced by /I-oxidation of 11-hydroxy dodecanoic acid, which may be produced directly by w-1-hydroxylation of dodecanoic acid. (25) and riboflavin responsive multiple acyl-CoA dehydrogenation defect (15) is the urinary excretion of pathologic amounts of the three dicarboxylic acids, adipic, suberic and sebacic acids. In some of the patients, the finding of 5-hydroxy hexanoic acid has also been reported (6,12,13,15), and in a single case 7-hydroxy octanoic and 9-hydroxy decanoic acids have been found (6, 24).…”

“…(25) and riboflavin responsive multiple acyl-CoA dehydrogenation defect (15) is the urinary excretion of pathologic amounts of the three dicarboxylic acids, adipic, suberic and sebacic acids. In some of the patients, the finding of 5-hydroxy hexanoic acid has also been reported (6,12,13,15), and in a single case 7-hydroxy octanoic and 9-hydroxy decanoic acids have been found (6, 24). Several workers including ourselves, have suggested that the dicarboxylic and w-1-hydroxy acid in these types of patients are formed, respectively, by w-and w-1-oxidation of the chain-length corresponding monocarboxylic acids, which are accumulated intracellularly due to a deficiency of medium-chained fatty acylCoA dehydrogenation (4, 13).…”