Lathyrism

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 Dhal, Khesari Dhal or Almorta) and to a lesser degree with Lathyrus cicera, Lathyrus ochrus and Lathyrus clymenum 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, BOAA) causes paralysis, characterized by lack of strength in or inability to move the lower limbs. A unique symptom of lathyrism is the emaciation of gluteal muscles (buttocks). ODAP is a poison of mitochondria leading to excess cell death, especially in motor neurons.

Prevalence
This disease is prevalent in some areas of Bangladesh, Ethiopia, India and Nepal, and affects more men than women. The reason for this is unclear, female hormones have been suggested to offer a measure of protection, but also less food allocation and less oxidatively stressful activity [work] are plausible.

Causes


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 and 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.

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.

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. 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.

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.

In Spain, a seed mixture known as comuña 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.

Related conditions
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.