URINARY ORGANIC-ACIDS IN INFANT MALNUTRITION

The metabolic derangements in severe protein-energy malnutrition (PEM) are only partially known, due to the limitations of blood collection in these patients. Urinary excretion of organic acids was studied by g as chromatography-mass spectrometry in 39 infants with four types of P EM: 1) upon hospital admission, as soon as eventual infections had bee n cleared, and salt and water deficits corrected, but before oral feed ing was started; 2) after start of protein alimentation; 3) on the day of discharge. All of the patients showed an increased excretion of va rious organic acids at some point of their hospital stay, regardless o f the clinical type of PEM. In nearly half of the malnourished childre n, results were suggestive of blocks in the pathways of propionate (15 .4% with increased methylmalonate and 25.6% with 2-methylcitrate), of fatty acid beta-oxidation (30.8% with raised dicarboxylic acids with l ow or low normal S-hydroxybutyrate), or of both pathways (12.8%). Thes e abnormalities may have been caused by cofactor deficiencies (biotin, vitamin B-12, riboflavin, carnitine, niacin). Dicarboxylic acids were excreted in high amounts since the initial sample, probably due to in creased mobilization of fatty acids. Increased 2-methylcitrate and met hylmalonate excretion was observed more frequently once patients start ed to be orally fed. The accumulation of potentially toxic acyl-CoA pr ecursors of these compounds could contribute to the known clinical wor sening of some malnourished infants after suddenly increased protein i ntake. Other less specific metabolites, such as 3-hydroxybutyrate, lac tate, 4-hydroxyphenylactate, fumarate, succinate, and 4-hydroxyphenyla cetate, were also abnormally excreted in some patients. The analysis o f urinary organic acids provides a new approach for the metabolic stud y of PEM and may have diagnostic and therapeutic implications.