INTRODUCTION: We describe a rare cause of severe metabolic acidosis associated with multiple acyl coA deficiency.
CASE PRESENTATION: A 42 year old female presented with 3 day history of nausea, vomiting, chest pain and dyspnea. She denied fever, cough, diarrhea, abdominal pain, ingestion of alcohol or other drugs. She had started an exercise program the week prior to presentation. Medical history was significant for similar presentation 10 years prior. On presentation, she was confused, tachycardic and tachypneic. Metabolic acidosis was present with increased anion gap and osmolar gap. Circulatory failure developed with tachycardia and hypotension requiring IV fluids, administration of bicarbonate and vasopressor support. Due to concern for toxic alcohol ingestion fomepizole was started along with hemodialysis. Toxicology analysis of blood and urine were negative and urine did not show oxalate crystals. Ketonuria was present and thought to be secondary to starvation. Dextrose-containing infusion was started. Urine inorganic acid analysis showed markedly elevated excretion of glutaric acid, 2-OH glutaric acid and 2-OH glutaric lactone, ethylmalonic acid, isovalerylglycine, hexanoylglycine and suberylglycine in addition to of 3-hydroxy butyric acid and acetoacetic acid.
DISCUSSION: This patient was found to have gross dicarboxylic aciduria due to multiple acyl coA dehydrogenase deficiency (MADD). This condition is a rare in-born error of lipid metabolism that is transmitted as an autosomal recessive trait. Fatty acids are metabolized by using β-oxidation reactions which are directly coupled to coenzyme Q of the electron transfer chain through electron transfer flavoprotein (ETF) and electron transfer flavoprotein-ubiquinone (co-enzyme Q) oxidoreductase (ETF-QO). Defects in these flavoproteins affects oxidation of fatty acids and the metabolism of the amino acids lysine and leucine. Alternative pathways for long chain fatty acid oxidation produce dicarboxylic acids that accumulate and are eliminated in the urine. Any condition that encourages increased fatty acid metabolism such as starvation can result in severe metabolic acidosis.
CONCLUSIONS: MADD should be considered in differential diagnosis of severe metabolic acidosis with increased anion gap.
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Reference #2 Shetty AK, Craver RD, Harris JA, Schmidt-Sommerfeld E. Delayed diagnosis of fatal medium-chain acyl-CoA dehydrogenase deficiency in a child. Pediatr Emerg Care. 1999 Dec;15(6):399-401.
Reference #3 Brus F, Smit GP, Knoester H, Reijngoud DJ.Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in 2 patients with symptoms of Reye syndrome. Tijdschr Kindergeneeskd. 1988 Jun;56(3):132-7.
DISCLOSURE: The following authors have nothing to disclose: Aanchal Kapoor, Madhu Sasidhar
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