Lathyrism

Lathyrism
Thanks to the grasspea, an aquatint print by Goya showing the use of grasspea as a famine food but also highlighting its effects (crippled woman lying on the floor)
Classification and external resources
Specialty emergency medicine
ICD-10 T62.2
ICD-9-CM 988.2
DiseasesDB 32679
Patient UK Lathyrism
MeSH D007842

Lathyrism or neurolathyrism is a neurological disease of humans and domestic animals, caused by eating certain legumes of the genus Lathyrus. This problem is mainly associated with Lathyrus sativus (also known as Grass pea, Kesari Dal, Khesari Dal or Almorta) and to a lesser degree with Lathyrus cicera, Lathyrus ochrus and Lathyrus clymenum[1] containing the toxin ODAP.

The lathyrism resulting from the ingestion of Lathyrus odoratus seeds (sweet peas) is often referred to as odoratism or osteolathyrism, which is caused by a different toxin (beta-aminopropionitrile) that affects the linking of collagen, a protein of connective tissues.

Symptoms

The consumption of large quantities of Lathyrus grain containing high concentrations of the glutamate analogue neurotoxin β-oxalyl-L-α,β-diaminopropionic acid (ODAP, also known as β-N-oxalyl-amino-L-alanine, or BOAA) causes paralysis, characterized by lack of strength in or inability to move the lower limbs, and may involve pyramidal tracts producing signs of upper motor neuron damage. The toxin may also cause aortic aneurysm.[2][3] A unique symptom of lathyrism is the atrophy of gluteal muscles (buttocks). ODAP is a poison of mitochondria,[3] leading to excess cell death, especially in motor neurons. Children can develop bone deformity and reduced brain development.[4]

Prevalence

This disease is prevalent in some areas of Bangladesh, Ethiopia, India and Nepal,[5] and affects more men than women, . Men between 25 and 40 are particularly vulnerable.[4]

Causes

Glutamic acid
Oxalyldiaminopropionic acid

The toxicological cause of the disease has been attributed to the neurotoxin ODAP which acts as a structural analogue of the neurotransmitter glutamate. Ingestion of legumes containing the toxin results mostly from ignorance of their toxicity but can also be because poor people lack resources to detoxify.[4] Lathyrism usually occurs where the despair of poverty and malnutrition leaves few other food options. Lathyrism can also be caused by food adulteration.

Prevention

Recent research suggests that sulfur amino acids have a protective effect against the toxicity of ODAP.[6]

Eating the chickling pea with grain having high concentrations of sulphur-based amino acids reduces the risk of lathyism if grain is available. Food preparation is also an important factor. Toxic amino acids are readily soluble in water and can be leached. Bacterial (lactic acid) and fungal (tempeh) fermentation is useful to reduce ODAP content. Moist heat (boiling, steaming) denatures protease inhibitors which otherwise add to the toxic effect of raw grasspea through depletion of protective sulfur amino acids. During times of drought and famine water for steeping and fuel for boiling is frequently also in short supply. Poor people sometimes know how to reduce the chance of developing lathyrism but face a choice between risking lathyrism or starvation.[4]

The underlying cause for excessive consumption of grasspea is a lack of alternative food sources. This is a consequence of poverty and political conflict. The prevention of lathyrism is therefore a socio-economic challenge.

Historical occurrence

The first mentioned intoxication goes back to ancient India and also Hippocrates mentions a neurological disorder 46 B.C. in Greece caused by Lathyrus seed.[7] Lathyrism was occurring on a regular basis.

During the Spanish War of Independence against Napoleon, grasspea served as a famine food. This was the subject of one of Francisco de Goya's famous aquatint prints titled Gracias a la Almorta ("Thanks to the Grasspea"), depicting poor people surviving on a porridge made from grasspea flour, one of them lying on the floor, already crippled by it.

During WWII, on the order of Colonel I. Murgescu, commandant of the Vapniarka concentration camp in Transnistria, the detainees - most of them Jews - were fed nearly exclusively with fodder pea. Consequently, they became ill from lathyrism.[8]

In the film Ashes [English title] by Andrzej Wajda based on the novel Popioly [Polish title] translated as Lost army [English title] by Stefan Żeromski spanning the period 1798–1812, a horse is poisoned by grain from a Spanish village. The footage of the horse losing control of its hind legs suggests that it was fed with Almortas.

Modern occurrence

During the post-war period in Spain, there were several outbreaks of lathyrism, caused by the shortage of food, which led people to consume excessive amounts of Almorta flour.[9]

In Spain, a seed mixture known as comuña[10] consisting of Lathyrus sativus, L. cicera, Vicia sativa and V. ervilia provides a potent mixture of toxic amino acids to poison monogastric (single stomached) animals. Particularly the toxin beta-cyanoalanine from seeds of V. sativa enhances the toxicity of such a mixture through its inhibition of sulfur amino acid metabolism [conversion of methionine to cysteine leading to excretion of cystathionine in urine] and hence depletion of protective reduced thiols. Its use for sheep does not pose any lathyrism problems if doses do not exceed 50 percent of the ration.[11]

Ronald Hamilton suggested in his paper The Silent Fire: ODAP and the death of Christopher McCandless that Christopher McCandless may have died from starvation after being unable to hunt or gather food due to lathyrism induced paralysis of his legs caused by eating the seeds of Hedysarum alpinum.[12] In 2014, a preliminary lab analysis indicated that the seeds did contain ODAP.[13] However, a more detailed mass spectrometric analysis conclusively ruled out ODAP and lathyrism.[14] Further studies showed that McCandless' death can be attributed to amino acid L-Canavanine, proven to exist in Hedysarum alpinum.[15]

A related disease has been identified and named osteolathyrism, because it affects the bones and connecting tissues, instead of the nervous system. It is a skeletal disorder, caused by the toxin beta-aminopropionitrile (BAPN), and characterized by hernias, aortic dissection, exostoses, and kyphoscoliosis and other skeletal deformities, apparently as the result of defective aging of collagen tissue. The cause of this disease is attributed to beta-aminopropionitrile, which inhibits the copper-containing enzyme lysyl oxidase, responsible for cross-linking procollagen and proelastin. BAPN is also a metabolic product of a compound present in sprouts of grasspea, pea and lentils.[16] A disorder that is clinically similar is konzo.

References

  1. ↑ "Medical problems caused by plants: Lathyrism" at Prince Leopold Institute of Tropical Medicine online database
  2. ↑ William Howlett (2012). Neurology in Africa. pp. 248–249.
  3. 1 2 "Lathyrism". Egton Medical Information Systems Limited.
  4. 1 2 3 4 Lathyrism
  5. ↑ Spencer P. S.; Ludolph A. C.; Kisby G. E. (July 1993). "Neurologic diseases associated with use of plant components with toxic potential". Environmental Research. 62 (1): 106–113. doi:10.1006/enrs.1993.1095. PMID 8325256.
  6. ↑ Sriram K.; Shankar S.K.; Boyd M.R.; Ravindranath V. (1998). "Thiol Oxidation and Loss of Mitochondrial Complex I Precede Excitatory Amino Acid-Mediated Neurodegeneration". The Journal of Neuroscience. 18 (24): 10287–10296. PMID 9852566.
  7. ↑ Mark V. Barrow; Charles F. Simpson; Edward J. Miller (1974). "Lathyrism: A Review". The Quarterly Review of Biology. 49 (2): 101–128. doi:10.1086/408017. JSTOR 2820941. PMID 4601279.
  8. ↑ isurvived.org: The Holocaust in Romania Under the Antonescu Government, by Marcu Rozen.
  9. ↑ "AZCOYTIA, Carlos (2006): "Historia de la Almorta or el veneno que llegó con el hambre tras la Guerra Civil Española". ''HistoriaCocina''". Historiacocina.com. Retrieved 2013-09-23.
  10. ↑ The etymological origin of this name is from "común" (common) in its meaning of mixture, referring to the mix of seeds obtained when cleaning the grain and which contaminate the main grain, generally wheat.
  11. ↑ J.E. Hernández Bermejo; J. León (1994). Neglected crops 1492 from a different perspective. Rome: Food and Agriculture Organization of the United Nations. ISBN 92-5-103217-3.
  12. ↑ Ronald Hamilton (September 12, 2013). "ODAP and the death of Christopher McCandless".
  13. ↑ newyorker.com
  14. ↑ newyorker.com
  15. ↑ Jon Krakauer et. al. (March 2015). "Presence of L-Canavanine in Hedysarum alpinum seeds and its potential role in the death of Chris McCandless".
  16. ↑ COHN, D.F. (1995) "Are other systems apart from the nervous system involved in human lathyrism?" in Lathyrus sativus and Human Lathyrism: Progress and Prospects. Ed. Yusuf H, Lambein F. University of Dhaka. Dhaka pp. 101-2.
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