Late-Onset Multiple Acyl-CoA Dehydrogenase Deficiency Presenting as Hyperammonemia and Encephalopathy: Case Series

Abstract

Background: Multiple acyl-CoA dehydrogenase deficiency (MADD) is an inherited metabolic disorder (IMD) that affects the electron transfer chain and fatty acid oxidation. The late-onset form of MADD has a heterogenous clinical presentation that typically results in episodic lethargy, hypoglycemia, acidosis, and rhabdomyolysis during metabolic decompensations. Purpose: In this case report series we describe three cases of late-onset MADD presenting with hyperammonemia and encephalopathy, a less frequent but severe complication. Methods: the medical records of three patients with MADD and hyperammonemia were retrospectively analyzed for details surrounding their presentation and workup. Results: One patient had hyperammonemia to 445 μmol/L, obtundation, and seizures, requiring venovenous hemodialysis. Two patients had abnormal brain imaging findings. Two of the cases were initially diagnosed as hepatic encephalopathy, but treatment for this did not reverse the hyperammonemia. Workup for IMDs revealed biochemical profiles consistent with MADD, with non-diagnostic genetic testing. MADD-directed therapy led to a reversal of hyperammonemia and return to neurologic baseline of all patients. Conclusion: This series highlights hyperammonemia as a presentation of late-onset MADD, a potentially lethal but treatable disorder.