Etiology of Konzo, epidemic spastic paraparesis associated with cyanogenic glycosides in cassava: role of thiamine deficiency?
Konzo is a syndrome of symmetrical, non-progressive, non-remitting spastic paraparesis occurring in epidemic and endemic forms in several countries in Africa, invariably associated with monotonous consumption of inadequately processed bitter cassava roots (Manihot esculenta) with very minimal protein supplementation. Despite numerous epidemiological, clinical and biochemical studies by authors in several countries aimed at elucidating the etiological mechanisms of Konzo, the etiology remains unknown. High cyanide consumption with low dietary sulfur intake due to almost exclusive consumption of insufficiently processed bitter cassava roots was proposed as the cause of Konzo, but there has been no evidence of a causal association between cyanide consumption and Konzo. In this paper a new etiological mechanism of thiamine deficiency is presented, based on detailed review of the epidemiological, clinical and biochemical features of Konzo. It is postulated that in Konzo patients, a severe exacerbation of thiamine deficiency results from the inactivation of thiamine that occurs when, in the absence of dietary sulfur-containing amino acids; the sulfur in thiamine is utilized for the detoxification of cyanide consumed in improperly processed bitter cassava. Thiamine is known to be rendered inactive when the sulfur in its thiazole moiety is combined with hydrogen cyanide. This hypothesis may stimulate studies examining the role of thiamine in the etiology of Konzo, and may lead to the formulation of strategies for the prevention and treatment of this debilitating disease.
Adamolekun
Bola
B
Department of Neurology, University of Tennessee Health Science Center, 855 Monroe Avenue, Memphis, TN 38163, USA. badamole@uthsc.edu
D000349:Africa; D000603:Amino Acids, Sulfur / Q000172:deficiency; D001925:Brain Damage, Chronic / Q000209:etiology; D002524:Cerebellar Ataxia / Q000209:etiology*; D003486:Cyanides / Q000009:adverse effects / Q000032:analysis; D004032:Diet / Q000009:adverse effects*; D058872:Epidemics; D006801:Humans; D002365:Manihot / Q000737:chemistry*; D009901:Optic Nerve Diseases / Q000209:etiology; D020336:Paraparesis, Spastic / Q000209:etiology* / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000209:etiology; D018517:Plant Roots / Q000737:chemistry; D013577:Syndrome; D013832:Thiamine Deficiency / Q000209:etiology* / Q000473:pathology; D013861:Thiocyanates / Q000032:analysis / Q000378:metabolism
D000603:Amino Acids, Sulfur; D003486:Cyanides; D013861:Thiocyanates; C031760:thiocyanate