SummaryWhen amino acids were infused at a rate of 4 g/kg/day, an infant with hypoglycemia, metabolic acidemia and chronic regurgitation showed hypersarcosinemia and excreted abnormal amounts of sarcosine, isovalerylglycine, isobutyrylglycine, &agr;‐methylbutyrylglycine, and &bgr;‐hydroxyisovaleric, glutaric, &agr;‐hydroxyglutaric, methylsuccinic, and &agr;‐hydroxyisobutyric acids in urine. On all other occasions, when protein intake was lower and lipid intake higher, urine organic acids were dominated by methylsuccinic, ethylmalonic, and &agr;‐hydroxyglutaric acids, and hypersarcosinemia was absent. Autopsy showed severe fatty changes in liver, kidneys, and skeletal muscle. A previous female sibling had died with similar autopsy findings at 4 days of age. While activity of glutaryl‐CoA dehydrogenase was completely deficient in liver and almost completely so in kidney, it was normal in cultured fibroblasts in the presence of flavin adenine dinucleotide (FAD) and only marginally low in its absence. Incorporation of d‐(2‐14C) riboflavin into flavin mononucleotides (FMN) and FAD by kidney tissue was normal.The authors conclude that this disorder is not due to generalized deficiency of glutaryl‐CoA dehydrogenase or to a defect in FAD synthesis. The amino and organic acid abnormalities noted are most consistent with a defect in the flavoprotein which transfers electrons from the FAD of sarcosine and acyl‐CoA dehydrogenases into the respiratory chain, although a defect in intercompartmental transfer of C4‐5 acyl CoA esters across cell membranes is not excluded.The variability of the organic aciduria, which possibly reflects changes in protein and fat intake, suggests that a previous name for this disorder,i.e., glutaric aciduria type II, is inappropriate and should be replaced, perhaps by “multiple acyl‐CoA dehydrogenase deficiency.”SpeculationWhat appears to be simultaneous deficiency of several acyl‐CoA dehydrogenases may be caused by a number of different primary gene defects; the presence of hypersarcosinemia and/or sarcosinuria may delineate a subtype due to deficiency of an electron carrier flavoprotein. Further, the presence of organic aciduria may define a form of hypersarcosinemia more likely to be associated with phenotypic abnormalities than isolated deficiency of the sarcosine dehydrogenase apoenzyme.