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Contents 2,5 Differential Diagnosis of in the Same Population Working together to eliminate cyanide poisoning, konzo and tropical ataxic neuropathy (TAN). Cassava Cyanide Diseases Network Issue Number 12, December 2008 and konzo if both disorders occurred Contents 2,5 Differential diagnosis of in the same population. konzo from other tropical Konzo and TAN have been Differential diagnosis of diseases: a review attributed to dietary cyanide konzo from other tropical exposure from consumption of diseases: a review .............. 1 Konzo with its upper motor neurone insufficiently processed cassava manifestations can be confused with roots, but rates of exposure differ in 7 other diseases and differential both diseases. In contrast to konzo, Comparison of cassava flour diagnosis is important. Using the TAN is a progressive disorder with and gari .................................... 2 WHO criteria, konzo by its spastic slow onset that mainly affects older paraparesis can easily be adults. Furthermore, konzo involves distinguished from causes of flaccid damage to upper motor neurones Outbreak of konzo disease in paraplegia such as poliomyelitis, without sensory involvement, health region No. 2 of the leprosy or trauma.1 The commonest whereas TAN is mainly caused by damage of sensory neurons in the Central African Republic ....... 3 neurological diseases to be considered in its differential spinal cord resulting in ataxia. TAN diagnoses include neurolathyrism, rarely progresses to inability to walk, Endomyocardial fibrosis: Tropical Ataxic Neuropathy (TAN) whereas walking difficulties are the primary symptom of konzo and a cause still unknown ................ 4 and Tropical Spastic Paraparesis/ HTL V-I Associated Myelopathy high proportion of the konzo- (TSP/HAM) (see Table 1). affected subjects are unable to walk. About half of the TAN cases have Konzo is clinically very similar to optic atrophy which is rare among konzo cases. About one in five TAN CCDN Coordinator: neurolathyrism but differs from TAN 2-5 cases has exaggerated reflexes, a Dr. J. Howard Bradbury and TSP/HAM. The socio- Botany and Zoology, School of Biology, economic conditions of konzo and sign that occurs in all konzo 1,2 Australian National University neurolathyrism patients are very cases. Canberra ACT 0200, Australia similar as well. Both diseases can Phone: +61-2-6125 0775 be considered a sign of poverty, TSP/HAM is clinically possible to E-mail: [email protected] monotonous unbalanced diet and distinguish from both konzo and illiteracy.6 Neurolathyrism only neurolathyrism, although the clinical Coordinating Group: differs from konzo with the features of TSP/HAM include typical Julie Cliff, Ian Denton, Humberto somewhat higher age of onset, signs that are similar to both Muquingue, Arnaldo Cumbana, Dulce diseases such as weakness in the Nhassico predominance of males among the affected, sphincter involvement in legs, hyperflexia, clonus and extensor plantar responses. Country Contacts: some cases and the absence of 2 TSP/HAM is characterised by a Cameroon: E.E Agbor; cranial nerve involvement. There is no geographical overlap between chronic progressive spastic D.R. Congo: D.D. Ngudi; the consumption of grass pea seed paraparesis with sphincter India: Bala Nambisan and K.T. Shenoy; and cassava roots and therefore disturbances, urinary incontinence Indonesia: A.Hidayat; there is no geographical overlap of and impotence. There is mild to no Mozambique: Anabela Zacarias; the two diseases. Combination of sensory loss and absence of spinal cord compression. Most but not all Nigeria: M.N.Adindu and P.N.Okafor grass pea and cassava in the diet could even amplify the risk. It would cases of TSP/HAM are seropositive 3,4,8,9 be difficult to make a differential for HTLV-1. Website: diagnosis between neurolathyrism www.anu.edu.au/BoZo/CCDN Table 1!:Characteristic features of four tropical myeloneuropathies (Tylleskär et al, 1994b) Konzo Tropical ataxic Neurolathyrism HTLV-I associated neuropathy myelopathy Geographical area Africa Africa Asia/ Africa Worldwide Occurrence Epidemic and endemic epidemic and endemic endemic endemic Highest prevalence 3 % 3 % 3 % 0.1 % Familial clustering yes yes yes yes Type of onset acute slow acute slow Course permanent progressive permanent progressive High incidence age group < 40 > 40 < 40 > 40 Main neurological findings: Gait abnormality Spastic paraparesis Ataxia Spastic paraparesis Spastic paraparesis Peripheral neuropathy no yes no common Sphincter involvement no no rare yes Optic atrophy rare yes no no Deafness no common no no Etiology Attributed to weeks of A t t r i b u t e d t o Caused by months of Caused by chronic high cyanide exposure prolonged, varying high grass pea HTLV-I infection from cassava cyanide exposure (Lathyrus sativus) from cassava consumption References Comparison of cassava flour has a slightly sour taste because of and gari the lactic acid present. 1 Howlett WP (1994). Konzo: A new human disease entity. Acta Horticulturae 375, 323-329. Total cyanide content. The sun Cassava flour is the major stable 2 Tylleskär T, Ruiza HT, Banea M, Howlett WP, drying of peeled cassava roots does product made from cassava roots in Aquilonius S-M, Persson L-Å, Rosling H (1994). not allow the enzyme linamarase to Similarities between konzo and lathyrism suggest Eastern, Southern and Central Africa, come into intimate contact with a common pathogenetic mechanism. In The whereas gari is the main stable linamarin, as occurs during gari grass pea and lathyrism.; Abegaz B. M., product made from cassava roots Haimanot R. T., Palmer, V. S., and Spencer, P. production, and hence linamarin is which is used in West Africa and also S., Eds.; Proceedings of the Second International only partially broken down in the flour, Lathyrus/ lathyrism Conference in Ethiopia; Third in southern Mozambique. World Medical Research Foundation: New York, which is found to contain linamarin at USA,; pp 26-32. average levels of 45 ppm.3 During a P r o c e s s i n g . Table A gives a 3 Cliff J, Nicala D (1997). Long term follow-up of drought the cassava plant produces comparison of the preparation of these konzo patients. Transactions of the Royal Society greatly increased amounts of of Tropical Medicine and hygiene, 91, 447 – 449. two products.1 Sun drying of cassava linamarin4 and the total cyanide 4 Zaninovic! V (2001). Similarities between roots is a very simple method that content of flour increases 2-4 fold to Tropical Spastic Paraparesis (TSP) and requires no mechanised equipment neurolathyrism. Lathyrus Lathyrism Newsletter, 2, >100 ppm.5 The World Health and is carried out by women at home. 11– 14. Organisation (WHO) safe level for total 5 By comparison gari is normally Lambein,F.,Defoort,B.,Kuo,Y-H, (2004). Konzo cyanide in cassava flour is 10 ppm.6 or neurolathyrism. Is there a difference? CCDN produced in a factory using a Levels of total cyanide in gari (present News No 3, 2-3. mechanical grinder to grate the peeled 6 as acetone cyanohydrin) range from 0- Getahun H, Lambein F, Vanhoorne M, Van Der cassava roots, a press for dewatering Stuyft (2002).Pattern and associated factors of 40 ppm with mean values of 15-20 and the roasting process is done by the neurolathyrism epidemic in Ethiopia. Tropical ppm.5 Medicine and International Health, 7, 118 – 124. women. 7 Howlett WP, Brubaker GR, Mlingi N, Rosling H Cassava flour in water is neutral (pH Availability of cyanogens in the (1990). Konzo an upper motor neurone disease about 6.5), whereas gari in water is body. Acetone cyanohydrin is studied in Tanzania. Brain, 113, 223 – 235. acidic (pH 4.1), due to lactic acid 8 completely decomposed to cyanide Tylleskär T (1994). The causation of konzo. fermentation that occurs during Studies on a paralytic disease in Africa. Acta under the alkaline conditions present prolonged processing of the wet Universitatis Upsaliensis. Comprehensive in the human gut, whereas linamarin is Summaries of Uppsala Dissertations from the cassava mash. The long processing stable under these conditions and Faculty of Medicine 413, 67 pp. allows the enzyme linamarase to 9 only about 50% is absorbed in the Cassab J, Penalva-de-Oliveira AC (2000). The hydrolyse linamarin completely to pathogenesis of tropical spastic parparasesis/ body.7 Thus the total cyanide acetone cyanohydrin, which is human T-cell leukemia type I-associated absorbed by the body from cassava myelopathy. Brazilian Journal of Medical and unstable above pH 5,2 and most of it flour under non-drought conditions is Biological Research, 33, 1395 – 1401. breaks down spontaneously to about 22.5 ppm and from gari about acetone and hydrogen cyanide (HCN) 15-20 ppm Delphin D. Ngudi & Fernand Lambein gas which partly escapes to the air. Ghent University, Belgium. The remainder of the HCN and nearly Methods to reduce cyanide. The [email protected]; all the acetone cyanohydrin is total cyanide content of cassava flour [email protected] removed in the roasting process, but is reduced 3-6 fold by mixing it with some remains in the final gari, which water, spreading it in a thin layer on a 2 CCDN News basket and leaving in the shade for comsumption of cyanide from gari at 4Bokanga M, Ekanayake IJ, Dixon AGO & Porto MCM, (1994) Acta Hort., 375, 131-139. five hours. This allows linamarase sub-lethal levels. TAN has also been 5 Cardoso AP, Mirione E, Ernesto M, Massaza F, present to hydrolyse linamarin to reported from a wide range of other Cliff J, Haque MR, & Bradbury JH, (2005) J. Food acetone cyanohydrin which breaks cassava-growing countries including Comp. Anal. 18, 451-460. 6 down spontaneously at pH 6.5 with Tanzania, West Indies and southern FAO/WHO, 1991. Joint FAO/WHO Food 8-10 10,14 Standards Programme. Codex Alimentarius liberation of HCN gas. The method India. Commission XII, Supp. 4, FAO, Rome, Italy. was checked out in northern 7 Carlsson L, Mlingi N, Juma A, Ronquist G & Mozambique and found to be very The key to the removal of these Rosling H, (1999) Food Chem.
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