Metabolomic Changes in Serum of Children with Different Clinical Diagnoses of Malnutrition.
BACKGROUND
Mortality in children with severe acute malnutrition (SAM) remains high despite standardized rehabilitation protocols. Two forms of SAM are classically distinguished: kwashiorkor and marasmus. Children with kwashiorkor have nutritional edema and metabolic disturbances, including hypoalbuminemia and hepatic steatosis, whereas marasmus is characterized by severe wasting. The metabolic changes underlying these phenotypes have been poorly characterized, and whether homeostasis is achieved during hospital stay is unclear.


OBJECTIVE
We aimed to characterize metabolic differences between children with marasmus and kwashiorkor at hospital admission and after clinical stabilization and to compare them with stunted and nonstunted community controls.


METHODS
We studied children aged 9-59 mo from Malawi who were hospitalized with SAM (n = 40; 21 with kwashiorkor and 19 with marasmus) or living in the community (n = 157; 78 stunted and 79 nonstunted). Serum from patients with SAM was obtained at hospital admission and 3 d after nutritional stabilization and from community controls. With the use of targeted metabolomics, 141 metabolites, including amino acids, biogenic amines, acylcarnitines, sphingomyelins, and phosphatidylcholines, were measured.


RESULTS
At admission, most metabolites (128 of 141; 91%) were lower in children with kwashiorkor than in those with marasmus, with significant differences in several amino acids and biogenic amines, including those of the kynurenine-tryptophan pathway. Several phosphatidylcholines and some acylcarnitines also differed. Patients with SAM had profiles that were profoundly different from those of stunted and nonstunted controls, even after clinical stabilization. Amino acids and biogenic amines generally improved with nutritional rehabilitation, but most sphingomyelins and phosphatidylcholines did not.


CONCLUSIONS
Children with kwashiorkor were metabolically distinct from those with marasmus, and were more prone to severe metabolic disruptions. Children with SAM showed metabolic profiles that were profoundly different from stunted and nonstunted controls, even after clinical stabilization. Therefore, metabolic recovery in children with SAM likely extends beyond discharge, which may explain the poor long-term outcomes in these children. This trial was registered at isrctn.org as ISRCTN13916953.
Department of Physiology and Experimental Medicine.
Valeria
V
Di Giovanni
Department of Physiology and Experimental Medicine.
Celine
http://orcid.org/0000-0002-6336-0906
C
Bourdon
Department of Physiology and Experimental Medicine.
Dominic X
DX
Wang
Program in Molecular Structure and Function.
Swapna
S
Seshadri
Department of Biomedical Sciences.
Edward
E
Senga
Department of Physiology and Experimental Medicine.
Christian J
CJ
Versloot
Department of Pediatrics and Child Health, and.|Global Child Health Group, Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, Netherlands.
Wieger
http://orcid.org/0000-0001-5825-2831
W
Voskuijl
Wilmer Eye Institute, John Hopkins University School of Medicine, Baltimore, MD.
Richard D
RD
Semba
Department of Pediatrics and Child Health, and.|National Institute of Aging, NIH, Baltimore, MD.
Indi
http://orcid.org/0000-0002-3364-6858
I
Trehan
National Institute of Aging, NIH, Baltimore, MD.
Ruin
R
Moaddel
Department of Pediatrics, Washington University in St. Louis, St. Louis, MO; and.
M Isabel
MI
Ordiz
Department of Physiology and Experimental Medicine.
Ling
L
Zhang
Program in Molecular Structure and Function.|Department of Biochemistry and Department of Molecular Genetics, University of Toronto, Toronto, Canada.
John
J
Parkinson
School of Public Health and Family Medicine, College of Medicine, University of Malawi, Blantyre, Malawi.|Department of Pediatrics, Washington University in St. Louis, St. Louis, MO; and.
Mark J
MJ
Manary
Department of Physiology and Experimental Medicine, robert.bandsma@sickkids.ca.|Division of Gastroenterology, Hepatology and Nutrition, and.|Centre for Global Child Health, Hospital for Sick Children, Toronto, Canada.|Department of Biomedical Sciences.
Robert Hj
RH
Bandsma
D015362:Child Nutrition Disorders / Q000097:blood* / Q000378:metabolism / Q000401:mortality; D002675:Child, Preschool; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007223:Infant; D007732:Kwashiorkor / Q000097:blood* / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D008297:Male; D055442:Metabolome; D011502:Protein-Energy Malnutrition / Q000097:blood* / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality
children; kwashiorkor; marasmus; metabolites; p180 kit; severe acute malnutrition; targeted metabolomics