title: Lower sulfurtransferase detoxification rates of cyanide in konzo-A tropical spastic paralysis linked to cassava cyanogenic poisoning.
abstract: Using a matched case-control design, we sought to determine whether the odds of konzo, a distinct spastic paraparesis associated with food (cassava) cyanogenic exposure in the tropics, were associated with lower cyanide detoxification rates (CDR) and malnutrition. Children with konzo (N=122, 5-17 years of age) were age- and sex-matched with presumably healthy controls (N=87) and assessed for motor and cognition performances, cyanogenic exposure, nutritional status, and cyanide detoxification rates (CDR). Cyanogenic exposure was ascertained by thiocyanate (SCN) concentrations in plasma (P-SCN) and urine (U-SCN). Children with a height-for-age z-score (HAZNCHS)<-2 were classified as nutritionally stunted. CDR was measured as time required to convert cyanide to SCN, and expressed as ms/μmol SCN/mg protein or as mmolSCN/ml plasma/min. Mean (SD) U-SCN in children with konzo was 521.9 (353.6) μmol/l and was, significantly higher than 384.6 (223.7) μmol/l in those without konzo. Conditional regression analysis of data for age- and sex- matched case-control pairs showed that konzo was associated with stunting (OR: 5.8; 95% CI: 2.7-12.8; p<0.01; N=83 paired groups) and higher U-SCN (OR: 1.1; 95% CI: 1.02-1.20 per 50-μmol increase in U-SCN; p=0.02; N=47 paired groups). After adjusting for stunting and U-SCN, the odds of developing konzo was reduced by 63% (95% CI: 11-85%, p=0.03; N=41 paired groups) for each 5mmol SCN/(ml plasma/min)-increase in CDR. Linear regression analysis indicated a significant association between BOT-2 or KABC-II scores and both the HAZNCHS z-score and the U-SCN concentration, but not the CDR. Our findings provide evidence in support of interventions to remove cyanogenic compounds from cassava prior to human consumption or, peharps, enhance the detoxification of cyanide in those relying on the cassava as the main source of food.
authors.affiliation: Department of Biomedical Sciences, University of Kinshasa, Congo-Kinshasa, Democratic Republic of the Congo.
authors.forename: K J
authors.initials: KJ
authors.lastname: Kambale
authors.affiliation: Department of Biology, University of Kinshasa, Congo-Kinshasa, Democratic Republic of the Congo; Institut National de Recherches Biomédicales (INRB), Congo-Kinshasa, Democratic Republic of the Congo.
authors.forename: E R
authors.initials: ER
authors.lastname: Ali
authors.affiliation: School of Public Health, University of Kinshasa, Congo-Kinshasa, Democratic Republic of the Congo.
authors.forename: N H
authors.initials: NH
authors.lastname: Sadiki
authors.affiliation: School of Public Health, University of Kinshasa, Congo-Kinshasa, Democratic Republic of the Congo.
authors.forename: K P
authors.initials: KP
authors.lastname: Kayembe
authors.affiliation: Department of Biomedical Sciences, University of Kinshasa, Congo-Kinshasa, Democratic Republic of the Congo.
authors.forename: L G
authors.initials: LG
authors.lastname: Mvumbi
authors.affiliation: Department of Biology, University of Kinshasa, Congo-Kinshasa, Democratic Republic of the Congo.
authors.forename: D L
authors.initials: DL
authors.lastname: Yandju
authors.affiliation: Department of Psychiatry and Neurology/Ophthalmology, Michigan State University, East Lansing, MI, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Boivin
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
authors.forename: G R
authors.initials: GR
authors.lastname: Boss
authors.affiliation: Graduate Programs in Human Nutrition, Oregon Health & Science University, Portland, OR, USA.
authors.forename: D D
authors.initials: DD
authors.lastname: Stadler
authors.affiliation: Department of Public Health and Preventive Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: W E
authors.initials: WE
authors.lastname: Lambert
authors.affiliation: Department of Public Health and Preventive Medicine, Oregon Health & Science University, Portland, OR, USA; Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, OR, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Lasarev
authors.affiliation: Department of Neurology, University of Kinshasa, Congo-Kinshasa, Democratic Republic of the Congo.
authors.forename: L A
authors.initials: LA
authors.lastname: Okitundu
authors.affiliation: Department of Tropical Medicine, University of Kinshasa, Congo-Kinshasa, Democratic Republic of the Congo; Institut National de Recherches Biomédicales (INRB), Congo-Kinshasa, Democratic Republic of the Congo.
authors.forename: D
authors.initials: D
authors.lastname: Mumba Ngoyi
authors.affiliation: School of Public Health, University of Kinshasa, Congo-Kinshasa, Democratic Republic of the Congo; National Nutrition Program, Ministry of Health, Congo-Kinshasa, Democratic Republic of the Congo.
authors.forename: J P
authors.initials: JP
authors.lastname: Banea
authors.affiliation: Department of Neurology, University of Kinshasa, Congo-Kinshasa, Democratic Republic of the Congo; Institut National de Recherches Biomédicales (INRB), Congo-Kinshasa, Democratic Republic of the Congo; Department of Neurology, Oregon Health & Science University, Portland, OR, USA. Electronic address: tshalad@ohsu.edu.
authors.forename: D D
authors.initials: DD
authors.lastname: Tshala-Katumbay
mesh_terms: D000293:Adolescent; D000704:Analysis of Variance; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000209:etiology; D003486:Cyanides / Q000633:toxicity*; D005260:Female; D006801:Humans; D008297:Male; D000068079:Motor Disorders / Q000209:etiology; D009570:Nitriles; D015493:Paraparesis, Tropical Spastic / Q000139:chemically induced* / Q000378:metabolism; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D013466:Sulfurtransferases / Q000378:metabolism*
chemical_list: D003486:Cyanides; D009570:Nitriles; C011206:cyanogen; D013466:Sulfurtransferases
keywords: Cassava; Cyanide detoxification; Konzo; Neurotoxicity; Rhodanese; Sulfurtransferases