FACULTY OF MEDICINE
Department of Basic Sciences
BIOCHEMISTRY DEPARTMENT

By
KAMJ;JALE KIKANDAU Jackin
Master's in Molecular Biology
Works Manager

Thesis defended with a view to obtaining the title of Doctor of Science,

Promoter

Professor MUMBA NGOYI Dieudonné

Co-Promoters:

• Professor MVUMBI LELO Georges
• Professor TSHALA KA TUMBA Y Désiré

SUMMARY

Context

Konzo is a toxico-nutritional disease associated with the consumption of poorly detoxified bitter cassava products. It affects children three years and older, and women of childbearing age. The elucidation
of its physiopathogenesis is incomplete due to the lack of reliable biomarkers.

Objective

To determine some biomarkers involved in the pathogenesis of konzo in order to contribute to its understanding.

Methods

Three studies were carried out in Kahemba. The first assessed the degree of exposure to cyanogenic substances by measuring cyanide in cassava flour and thiocyanate in urine; the second
allowed to evaluate the capacity of hydrocyanic detoxification in humans, taking into account their nutritional status, by measuring the activity of rhodanese; and the third evaluated the oxidative stress in konzo, by measuring serum isoprostanes.

Results

Mean urinary thiocyanate values were above the threshold for no risk of konzo. They were 382.48 ± 226.30 umol/L in non-konzo subjects and 520.43 ± 355 umol/L in subjects
konzo. The average cyanide (CN) level in the flour samples collected was 92.22 (± 56.21) mg HCN/kg dry weight, which was significantly higher than the FAO/WHO safety standard of 10 mg
of HCN/Kg dry weight. The activity of cyanide to thiocyanate conversion by rhodanese was low in konzo and malnourished subjects: mean CDR: 420.1 (±201) mS/(111) mISCN/mg protein. The mean serum level of 8,12-iso-PF2a isoprostanes in konzo children, 0.5 (±0.2) was higher than in non-konzo children, 0.3 (±0.1) (p= 0.04).

Conclusion

In light of different assessments of the markers used, including CN, urinary thiocyanate, rhodanese, HAZNCHS z-score and isoprostanes, the results reveal values that deviate from the values considered normal in sick subjects compared to non-sick subjects.
The occurrence of konzo is associated with cassava cyanide exposure, chronic malnutrition, and low detoxification rates. Keywords: biomarkers, poisoning, biological diagnosis, konzo disease, bitter cassava.

ABSTRACT

Context

Konzo is a toxico-nutritional disease associated with the consumption of mal-detoxified bitter cassava. It affects children of three years old and women at the age of procreation. The elucidation of physiopathology
is incomplete due to the lack reliable biomarkers.

Objective

To elucidate the physiopathogenesis of konzo by determining the biomarkers involved in its genesis.

Method

Tree crossed studies were conducted in Kahemba. The first study evaluated the degree of ex po sure to cyanogenic substances by the cyan ide' measurement in the cassava flour and the thiocyanate in the urine; the second helped to evaluate the capacity of cyanhydric detoxification among the cases study taking into account its nutritional status, by the measure of activity of the rhodanese; and the third study evaluated the oxidative stress in the konzo, by the measurement of ceric isoprostanes.

Results

The mean values of urinary thiocyanate CU-SCN) were superior to the low limit of absence of risk of konzo. They varied between 382.48 ±226.30 umol/L for the subjects without ker-zo and 520.43 ±355 umol/L to the
children with konzo. The rate of cyauide (CN) in the sam pIes of flour varied between 30 and 200 mg of HCN/Kg. That showed the exposure to cyanhydric intoxication with regard to FAO/OMS security norm which is
10 mg of HCN/Kg of dry weight. The activity of the transformation of cyanide into thiocyanate, by rhodanese, was weak among the konzo cases and the rnal-fed cases. \:'f_heoverage ceric rate of isoprostanes of konzo
children was superior campared to that without konzo.

Conclusion

ln the light of different evaluation of the markers used, in particular. cyanide, urinary thiocyanate, rhodanese, HAZNCHS z-score as weil as isoprostanes, the results reveal values which deviate from the values considered normal. The occurrence of konzo is associated with exposure to cassava cyan ide, chronic malnutrition and low detoxification rates. Key words: biomarkers, intoxication, biological diagnosis, bitter cassava and konzodisease.