Related Experiment Videos
Urinary organic acids in infant malnutrition
M Terán-García1, I Ibarra, A Velázquez
1Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas, Universidad Nacional Autonoma de México, México City.
Insights
Severe malnutrition in infants disrupts metabolism, indicated by abnormal organic acid levels in urine. These metabolic changes, potentially linked to cofactor deficiencies, offer new diagnostic insights for protein-energy malnutrition (PEM).
Area of Science:
- Biochemistry
- Pediatric Nutrition
- Metabolic Disorders
Background:
- Severe protein-energy malnutrition (PEM) presents complex metabolic disturbances that are not fully understood.
- Limitations in blood collection hinder comprehensive metabolic assessment in malnourished patients.
Purpose of the Study:
- To investigate urinary organic acid excretion in infants with severe PEM.
- To identify specific metabolic derangements and potential cofactor deficiencies associated with PEM.
- To explore the diagnostic utility of urinary organic acid analysis in PEM.
Main Methods:
- Urinary organic acid profiles were analyzed using gas chromatography-mass spectrometry in 39 infants with PEM.
- Samples were collected at admission, after initiating protein feeding, and at discharge.
- Metabolic pathways, including propionate metabolism and fatty acid beta-oxidation, were assessed.
Main Results:
- All patients exhibited increased excretion of various organic acids during hospitalization.
- Nearly half of the children showed evidence of metabolic blocks in propionate or fatty acid beta-oxidation pathways, or both.
- Elevated dicarboxylic acids were present from admission, suggesting increased fatty acid mobilization.
- Increased methylmalonate and 2-methylcitrate excretion was noted after oral feeding commenced, potentially linked to cofactor deficiencies.
Conclusions:
- Urinary organic acid analysis offers a novel approach to studying PEM metabolism.
- Abnormalities identified may be attributed to cofactor deficiencies (e.g., biotin, vitamin B12).
- Metabolic changes, particularly after protein refeeding, may contribute to clinical worsening in some PEM infants, highlighting diagnostic and therapeutic implications.
Abstract:
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 gas chromatography-mass spectrometry in 39 infants with four types of PEM: 1) upon hospital admission, as soon as eventual infections had been cleared, and salt and water deficits corrected, but before oral feeding was started; 2) after start of protein alimentation; 3) on the day of discharge. All of the patients showed an increased excretion of various organic acids at some point of their hospital stay, regardless of the clinical type of PEM. In nearly half of the malnourished children, 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 low or low normal 3-hydroxybutyrate), or of both pathways (12.8%). These abnormalities may have been caused by cofactor deficiencies (biotin, vitamin B12, riboflavin, carnitine, niacin). Dicarboxylic acids were excreted in high amounts since the initial sample, probably due to increased mobilization of fatty acids. Increased 2-methylcitrate and methylmalonate excretion was observed more frequently once patients started to be orally fed. The accumulation of potentially toxic acyl-CoA precursors of these compounds could contribute to the known clinical worsening of some malnourished infants after suddenly increased protein intake. Other less specific metabolites, such as 3-hydroxybutyrate, lactate, 4-hydroxyphenyllactate, fumarate, succinate, and 4-hydroxyphenylacetate, were also abnormally excreted in some patients. The analysis of urinary organic acids provides a new approach for the metabolic study of PEM and may have diagnostic and therapeutic implications.