Reduced production of sulfated glycosaminoglycans occurs in Zambian children with kwashiorkor but not marasmus.
BACKGROUND
Kwashiorkor, a form of severe malnutrition with high mortality, is characterized by edema and systemic abnormalities. Although extremely common, its pathophysiology remains poorly understood, and its characteristic physical signs are unexplained.


OBJECTIVE
Because kwashiorkor can develop in protein-losing enteropathy, which is caused by a loss of enterocyte heparan sulfate proteoglycan (HSPG), and previous observations suggest abnormal sulfated glycosaminoglycan (GAG) metabolism, we examined whether intestinal GAG and HSPG are abnormal in children with kwashiorkor.


METHODS
Duodenal biopsy samples collected from Zambian children with marasmus (n = 18), marasmic kwashiorkor (n = 8), and kwashiorkor (n = 15) were examined for expression of HSPG, GAGs, and immunologic markers and compared against reference samples from healthy UK control children. GAG and HSPG expression density and inflammatory cell populations were quantitated by computerized analysis.


RESULTS
The kwashiorkor group was less wasted and had a lower HIV incidence than did the other groups. All duodenal biopsy samples showed inflammation compared with the histologically uninflamed control samples. Biopsy samples from marasmic children had greater inflammation and greater CD3+ and HLA-DR (human leukocyte antigen DR)-positive cell densities than did samples from children with kwashiorkor. Expression of both HSPG and GAGs was similar between marasmic and well-nourished UK children but was markedly lower in children with kwashiorkor in both the epithelium and lamina propria. Although underglycosylated and undersulfated, epithelial syndecan-1 protein was normally expressed in kwashiorkor, which confirmed that abnormalities arise after core protein synthesis.


CONCLUSIONS
Intestinal HSPG loss occurs in kwashiorkor, which may precipitate protein-losing enteropathy to cause edema. If occurring systemically, impaired HSPG expression could cause several previously unexplained features of kwashiorkor. We speculate that a genetic predisposition to reduced HSPG biosynthesis may offer a contrasting selective advantage, by both diminishing protein catabolism during transient undernutrition and protecting against specific infectious diseases.
Amadi
Beatrice
B
Department of Paediatrics and Child Health, University Teaching Hospital of Lusaka, Lusaka, Zambia.
Fagbemi
Andrew O
AO
Kelly
Paul
P
Mwiya
Mwiya
M
Torrente
Franco
F
Salvestrini
Camilla
C
Day
Richard
R
Golden
Michael H
MH
Eklund
Erik A
EA
Freeze
Hudson H
HH
Murch
Simon H
SH
D000704:Analysis of Variance; D015415:Biomarkers; D016022:Case-Control Studies; D004386:Duodenum / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004487:Edema / Q000209:etiology; D005260:Female; D006025:Glycosaminoglycans / Q000378:metabolism*; D015658:HIV Infections / Q000150:complications / Q000453:epidemiology; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000150:complications / Q000378:metabolism; D007732:Kwashiorkor / Q000378:metabolism*; D008297:Male; D015995:Prevalence; D011502:Protein-Energy Malnutrition / Q000150:complications / Q000378:metabolism*; D011504:Protein-Losing Enteropathies / Q000209:etiology* / Q000378:metabolism; D015024:Zambia / Q000453:epidemiology
D015415:Biomarkers; D006025:Glycosaminoglycans; D019812:Heparan Sulfate Proteoglycans; C013786:A73025