One-carbon metabolism in children with marasmus and kwashiorkor

Thaddaeus May; Bethany de la Haye; Gabrielle Nord; Kevin Klatt; Kevin Stephenson; Sara Adams; Lucy Bollinger; Neil Hanchard; Erland Arning; Teodoro Bottiglieri; Kenneth Maleta; Mark Manary; Farook Jahoor

doi:10.1016/j.ebiom.2021.103791

One-carbon metabolism in children with marasmus and kwashiorkor

EBioMedicine. 2022 Jan:75:103791. doi: 10.1016/j.ebiom.2021.103791. Epub 2022 Jan 11.

Authors

Affiliations

¹ Children's Nutrition Research Center, Baylor College of Medicine, One Baylor Plaza, Houston TX, USA. Electronic address: tdmay@bcm.edu.
² Washington University in St. Louis School of Medicine, USA.
³ Stanford University School of Medicine, USA.
⁴ Children's Nutrition Research Center, Baylor College of Medicine, One Baylor Plaza, Houston TX, USA; Center for Precision Environmental Health, Baylor College of Medicine.
⁵ PATH, USA.
⁶ National Institutes of Health, USA; National Human Genome Research Institute, Nationl Institutes of Health.
⁷ Center of Metabolomics, Institute of Metabolic Disease, Baylor Scott and White Research Institute.
⁸ The University of Malawi College of Medicine, Malawi.
⁹ Children's Nutrition Research Center, Baylor College of Medicine, One Baylor Plaza, Houston TX, USA; The University of Malawi College of Medicine, Malawi; Washington University in St. Louis School of Medicine, USA.
¹⁰ Children's Nutrition Research Center, Baylor College of Medicine, One Baylor Plaza, Houston TX, USA.

Abstract

Background: Kwashiorkor is a childhood syndrome of edematous malnutrition. Its precise nutritional precipitants remain uncertain despite nine decades of study. Remarkably, kwashiorkor's disturbances resemble the effects of experimental diets that are deficient in one-carbon nutrients. This similarity suggests that kwashiorkor may represent a nutritionally mediated syndrome of acute one-carbon metabolism dysfunction. Here we report findings from a cross-sectional exploration of serum one-carbon metabolites in Malawian children.

Methods: Blood was collected from children aged 12-60 months before nutritional rehabilitation: kwashiorkor (N = 94), marasmic-kwashiorkor (N = 43) marasmus (N = 118), moderate acute malnutrition (N = 56) and controls (N = 46). Serum concentrations of 16 one-carbon metabolites were quantified using LC/MS techniques, and then compared across participant groups.

Findings: Twelve of 16 measured one-carbon metabolites differed significantly between participant groups. Measured outputs of one-carbon metabolism, asymmetric dimethylarginine (ADMA) and cysteine, were lower in marasmic-kwashiorkor (median µmol/L (± SD): 0·549 (± 0·217) P = 0·00045 & 90 (± 40) P < 0·0001, respectively) and kwashiorkor (0·557 (± 0·195) P < 0·0001 & 115 (± 50) P < 0·0001), relative to marasmus (0·698 (± 0·212) & 153 (± 42)). ADMA and cysteine were well correlated with methionine in both kwashiorkor and marasmic-kwashiorkor.

Interpretation: Kwashiorkor and marasmic-kwashiorkor were distinguished by evidence of one-carbon metabolism dysfunction. Correlative observations suggest that methionine deficiency drives this dysfunction, which is implicated in the syndrome's pathogenesis. The hypothesis that kwashiorkor can be prevented by fortifying low quality diets with methionine, along with nutrients that support efficient methionine use, such as choline, requires further investigation.

Funding: The Hickey Family Foundation, the American College of Gastroenterology, the NICHD, and the USDA/ARS.

Keywords: Choline; Edematous malnutrition; Methionine; Methyl donors; Nutritional edema; Severe acute malnutrition.

MeSH terms

Carbon
Child
Child, Preschool
Cross-Sectional Studies
Humans
Infant
Kwashiorkor* / etiology
Kwashiorkor* / metabolism
Malnutrition*
Protein-Energy Malnutrition* / metabolism

Substances

Carbon

Abstract

MeSH terms

Substances

Grants and funding