FACULTY OF SCIENCES
DEPARTMENT OF BIOLOGY

By
ALI EKANGU Rosine
Advanced Studies Diploma in Sciences, Head of Works in Biology

Thesis presented and publicly defended with a view to obtaining the degree of Doctor of Science
Group: Biology

Promoter: Professor Yandju Dembo Marie Claire
Co-promoters: Professor Tshala Katumbay Désiré
Professor Okitundu Luwa E-Andjafono Daniel

SUMMARY

Konzo is a pathology associated with hydrocyanic intoxication of dietary origin, the susceptibility factors and etiopathogenic mechanisms of which are not completely elucidated.
The objective is to elucidate the relationship between hydrocyanic detoxification capacities and susceptibility to konzo.
Two studies were conducted using a bioclinical and genetic approach in Kahemba, a region with a high prevalence of konzo. Enzymatic hydrocyanic detoxification in plasma, SCNU and SCNP levels were measured by enzymatic assay, colorimetry and spectrometry respectively. Thiosulfate sulfidetransferase/mercapto pyruvate thiosulfate sulfidetransferase (TSTIMPST) mutations were detected using the PCR sequencing strategy.
In statistical analysis, Student T, Mann-Whitney, Kruskal-Wallis tests, analysis of variance, Spearman correlation and logistic regression were applied at the significance level p:SO.05.
Conditional logistic regression analysis showed that: the odds of konzo were reduced by 63% (OR: 0.37; CI to 95%: 0.15 to 0.89, P = 0.03) for each increase in cyanide detoxification rate of 5 mmol SCN / (ml plasma / min).
Thirty-eight of the forty children carried a mutation in TST or MPST, or both. For TST, seven SNPs were found, six coding and one non-coding, while for MPST, four SNPs were found, three non-coding and one coding. Two SNPs were found to have possible deleterious effects in silico, p.Arg206Cys for TST and p.His317Tyr for MPST.
Reduced hydrocyanic detoxification capacity has been identified as a risk factor for the development of Konzo. Further studies should clarify the potential role of the TST and MPST SNPs found in susceptibility to Konzo.

Keywords : Cyanide, konzo, Genetic polymorphisms, MPST, TST.