Konzo: Neurology of a permanent and non-progressive motor neuron disorder associated with food (Cassava) toxicity

Abstract

Epidemics of neurodegenerative diseases putatively caused by food toxins have been reported under the tropics with no clear understanding of their pathogenetic mechanisms. These diseases include the disease named konzo, which has been well documented in sub-Saharan Africa, mostly among children and women of childbearing age. Konzo is highly prevalent in Congo-Kinshasa, Mozambique, Tanzania, Central African Republic, Angola, and Cameroun. The main clinical picture consists of a symmetrical, permanent and irreversible spastic paraparesis (motor neuron disease) with no signs of sensory or genitourinary impairments. Impaired cognition is possible but yet to be elucidated. The exact pathogenetic mechanisms of the disease remain unknown. Serological studies rule out the role of retroviruses such as the human lymphotropic viruses HIV-I/II or HTLV-I/II. Epidemiological studies consistently show an association between outbreaks of the disease and chronic dietary reliance on foodstuffs derived from insufficiently processed cyanogenic cassava (aka manioc or tapioca). Biochemical and toxicological studies suggest that the metabolites of linamarin (α-hydroxyisobutyronitrile β-d-glucopyranoside, the main cassava cyanogen), notably cyanide (mitochondrial toxin), thiocyanate (AMPA chaotropic agent), and cyanate (protein carbamoylating agent) may be important players in the pathogenesis of konzo. Experimental data suggest that thiol-redox and protein-folding mechanisms may also be perturbed. Factors of susceptibility including genetics, poor nutrition, and environmental exposures, or their interaction, have yet to be elucidated. There is no cure for konzo. Prevention of the disease remains of paramount importance.