Hypoaminoacidemia and Pyroglutamic Aciduria: Potential Biomarkers in Malnutrition-Related Hyperammonemia

Hyperammonemia is a medical emergency, and the cause must be identified quickly in order to treat appropriately. Malnutrition is a known risk factor for hyperammonemia; however, there are limited reliable lab indicators used to identify malnutrition. Early identification of the etiology of hyperammonemia is crucial to optimizing care, specifically reintroduction of appropriate amounts of protein into the diet. Herein, we discuss three patients with complex medical histories and clinical signs of malnutrition who presented with hyperammonemia. In all three patients, both hypoaminoacidemia and pyroglutamic aciduria were observed. Specifically, all patients had low tyrosine, tryptophan, methionine, and branched-chain amino acids. Recognizing this biochemical pattern could result in more rapid initiation of supplementing protein, a primary tenet of treatment in malnutrition-related hyperammonemia. We highlight the unique features of malnutrition-related hyperammonemia, propose mechanisms to explain the pattern, and suggest a framework for managing these cases.