Motor control and cognition deficits associated with protein carbamoylation in food (cassava) cyanogenic poisoning: Neurodegeneration and genomic perspectives

F. A. Rwatambuga, E. R. Ali, M. S. Bramble, J. E. Gosschalk, Morris Kim, D. L. Yandju, L. A. Okitundu, M. J. Boivin, J. P. Banea, S. K. Westaway, D. Larry, Eric Vilain, D. Mumba Ngoyi, D. D. Tshala-Katumbay

Research output: Contribution to journalArticlepeer-review

Abstract

A case-control design determined whether konzo, an upper motoneuron disease linked to food (cassava) toxicity was associated with protein carbamoylation and genetic variations. Exon sequences of thiosulfate sulfurtransferase (TST) or mercaptopyruvate sulfurtransferase (MPST), plasma cyanide detoxification rates, and 2D-LC-MS/MS albumin carbamoylation were assessed in 40 children [21 konzo-affected and 19 putatively healthy controls, mean (SD) age: 9.2 (3.0) years] subjected to cognition and motor testing using the Kaufman Assessment Battery and the Bruininks/Oseretsky Test, respectively. Konzo was significantly associated with higher levels of carbamoylated peptides 206–219 (LDELRDEGKASSAK, pep1) after adjusting for age, gender, albumin concentrations and BUN [regression coefficient: 0.03 (95%CI:0.02–0.05), p = 0.01]. Levels of pep1 negatively correlated with performance scores at all modalities of motor proficiency (r = 0.38 to 0.61; all p < 0.01) or sequential processing (memory)(r = - 0.59, p = 0.00) and overall cognitive performance (r = - 0.48, p = 0.00) but positively with time needed for cyanide detoxification in plasma (r = 0.33, p = 0.04). Rare potentially damaging TST p.Arg206Cys (rs61742280) and MPST p.His317Tyr (rs1038542246) heterozygous variants were identified but with no impact on subject phenotypes. Protein carbamoylation appears to be a reliable marker for cassava related neurodegeneration.

Original languageEnglish (US)
Article number111917
JournalFood and Chemical Toxicology
Volume148
DOIs
StatePublished - Feb 2021

Keywords

  • Carbamoylation
  • Cassava
  • Cyanide
  • Neurodegeneration
  • Sulfurtransferases

ASJC Scopus subject areas

  • Food Science
  • Toxicology

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