title: Reduced production of sulfated glycosaminoglycans occurs in Zambian children with kwashiorkor but not marasmus.
abstract: 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.
authors.affiliation: Department of Paediatrics and Child Health, University Teaching Hospital of Lusaka, Lusaka, Zambia.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Amadi
authors.forename: Andrew O
authors.initials: AO
authors.lastname: Fagbemi
authors.forename: Paul
authors.initials: P
authors.lastname: Kelly
authors.forename: Mwiya
authors.initials: M
authors.lastname: Mwiya
authors.forename: Franco
authors.initials: F
authors.lastname: Torrente
authors.forename: Camilla
authors.initials: C
authors.lastname: Salvestrini
authors.forename: Richard
authors.initials: R
authors.lastname: Day
authors.forename: Michael H
authors.initials: MH
authors.lastname: Golden
authors.forename: Erik A
authors.initials: EA
authors.lastname: Eklund
authors.forename: Hudson H
authors.initials: HH
authors.lastname: Freeze
authors.forename: Simon H
authors.initials: SH
authors.lastname: Murch
mesh_terms: 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
chemical_list: D015415:Biomarkers; D006025:Glycosaminoglycans; D019812:Heparan Sulfate Proteoglycans; C013786:A73025