Lathyrism
Encyclopedia
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 tissue
s.
(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.
, 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.
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.
s 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
) denature
s protease inhibitor
s 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.
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.
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.
, 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.
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...
Lathyrus
Lathyrus
Lathyrus is a genus of flowering plant species known as sweet peas and vetchlings. Lathyrus is in the legume family Fabaceae and contains approximately 160 species. They are native to temperate areas, with a breakdown of 52 species in Europe, 30 species in North America, 78 in Asia, 24 in...
. This problem is mainly associated with Lathyrus sativus
Lathyrus sativus
Lathyrus sativus, is a legume commonly grown for human consumption and livestock feed in Asia and East Africa. It is a particularly important crop in areas that are prone to drought and famine, and is thought of as an 'insurance crop' as it produces reliable yields when all other crops...
(also known as Grass pea, Kesari Dhal, Khesari Dhal or Almorta) and to a lesser degree with Lathyrus cicera
Lathyrus cicera
Lathyrus cicera is a species of wild pea known by the common names red pea and flatpod peavine. It is native to Europe, North Africa, and the Middle East, and it is known from other places as an introduced species. This is a hairless annual herb producing a slightly winged stem. The leaves are each...
, Lathyrus ochrus and Lathyrus clymenum containing the toxin
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...
ODAP
Oxalyldiaminopropionic acid
Oxalyldiaminopropionic acid is the neurotoxin responsible for lathyrism.-See also:* β-Methylamino-L-alanine, a related toxin...
. The lathyrism resulting from the ingestion of Lathyrus odoratus
Sweet pea
Sweet pea is a flowering plant in the genus Lathyrus in the family Fabaceae , native to the eastern Mediterranean region from Sicily east to Crete....
seeds (sweet peas) is often referred to as odoratism or osteolathyrism
Osteolathyrism
Osteolathyrism is a collagen cross-linking deficiency brought on by dietary over-reliance on the seeds of Lathyrus sativus. It is commonly seen in combination with neurolathyrism and angiolathyrism in impoverished areas where famine demands reliance on a crop with known detrimental effects...
, which is caused by a different toxin (beta-aminopropionitrile) that affects the linking of collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
, a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
of connective tissue
Connective tissue
"Connective tissue" is a fibrous tissue. It is one of the four traditional classes of tissues . Connective Tissue is found throughout the body.In fact the whole framework of the skeleton and the different specialized connective tissues from the crown of the head to the toes determine the form of...
s.
Symptoms
The consumption of large quantities of Lathyrus grain containing high concentrations of the glutamate analogue neurotoxin β-oxalyl-L-α,β-diaminopropionic acidOxalyldiaminopropionic acid
Oxalyldiaminopropionic acid is the neurotoxin responsible for lathyrism.-See also:* β-Methylamino-L-alanine, a related toxin...
(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
Emaciation
Emaciation occurs when an organism loses substantial amounts of much needed fat and often muscle tissue, making that organism look extremely thin. The cause of emaciation is a lack of nutrients, starvation, or disease....
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 BangladeshBangladesh
Bangladesh , officially the People's Republic of Bangladesh is a sovereign state located in South Asia. It is bordered by India on all sides except for a small border with Burma to the far southeast and by the Bay of Bengal to the south...
, Ethiopia
Ethiopia
Ethiopia , officially known as the Federal Democratic Republic of Ethiopia, is a country located in the Horn of Africa. It is the second-most populous nation in Africa, with over 82 million inhabitants, and the tenth-largest by area, occupying 1,100,000 km2...
, India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
and Nepal
Nepal
Nepal , officially the Federal Democratic Republic of Nepal, is a landlocked sovereign state located in South Asia. It is located in the Himalayas and bordered to the north by the People's Republic of China, and to the south, east, and west by the Republic of India...
, 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
Neurotoxin
A neurotoxin is a toxin that acts specifically on nerve cells , usually by interacting with membrane proteins such as ion channels. Some sources are more general, and define the effect of neurotoxins as occurring at nerve tissue...
ODAP
Oxalyldiaminopropionic acid
Oxalyldiaminopropionic acid is the neurotoxin responsible for lathyrism.-See also:* β-Methylamino-L-alanine, a related toxin...
which acts as a structural analogue of the neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
glutamate. Ingestion of legumes containing the toxin results mostly from ignorance of their toxicity and usually occurs where the despair of poverty
Poverty
Poverty is the lack of a certain amount of material possessions or money. Absolute poverty or destitution is inability to afford basic human needs, which commonly includes clean and fresh water, nutrition, health care, education, clothing and shelter. About 1.7 billion people are estimated to live...
and malnutrition
Malnutrition
Malnutrition is the condition that results from taking an unbalanced diet in which certain nutrients are lacking, in excess , or in the wrong proportions....
leaves few other food options. Lathyrism can also be caused by food adulteration.
Prevention
Recent research suggests that sulfur amino acidAmino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s 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
Lactic acid
Lactic acid, also known as milk acid, is a chemical compound that plays a role in various biochemical processes and was first isolated in 1780 by the Swedish chemist Carl Wilhelm Scheele. Lactic acid is a carboxylic acid with the chemical formula C3H6O3...
) and fungal (tempeh
Tempeh
Tempeh , or tempe , is a traditional soy product originally from Indonesia. It is made by a natural culturing and controlled fermentation process that binds soybeans into a cake form, similar to a very firm vegetarian burger patty...
) fermentation is useful to reduce ODAP content. Moist heat (boiling
Boiling
Boiling is the rapid vaporization of a liquid, which occurs when a liquid is heated to its boiling point, the temperature at which the vapor pressure of the liquid is equal to the pressure exerted on the liquid by the surrounding environmental pressure. While below the boiling point a liquid...
, steaming
Steaming
Steaming is a method of cooking using steam. Steaming is considered a healthy cooking technique and capable of cooking almost all kinds of food.-Method:...
) denature
Denaturation (biochemistry)
Denaturation is a process in which proteins or nucleic acids lose their tertiary structure and secondary structure by application of some external stress or compound, such as a strong acid or base, a concentrated inorganic salt, an organic solvent , or heat...
s protease inhibitor
Protease inhibitor
Protease inhibitor can refer to:* Protease inhibitor : a class of medication that inhibits viral protease* Protease inhibitor : molecules that inhibit proteases...
s 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
Poverty
Poverty is the lack of a certain amount of material possessions or money. Absolute poverty or destitution is inability to afford basic human needs, which commonly includes clean and fresh water, nutrition, health care, education, clothing and shelter. About 1.7 billion people are estimated to live...
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 HippocratesHippocrates
Hippocrates of Cos or Hippokrates of Kos was an ancient Greek physician of the Age of Pericles , and is considered one of the most outstanding figures in the history of medicine...
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
Peninsular War
The Peninsular War was a war between France and the allied powers of Spain, the United Kingdom, and Portugal for control of the Iberian Peninsula during the Napoleonic Wars. The war began when French and Spanish armies crossed Spain and invaded Portugal in 1807. Then, in 1808, France turned on its...
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
Andrzej Wajda
Andrzej Wajda is a Polish film director. Recipient of an honorary Oscar, he is possibly the most prominent member of the unofficial "Polish Film School"...
based on the novel Popioly
The Ashes (film)
The Ashes is a 1965 Polish drama film directed by Andrzej Wajda. It was entered into the 1966 Cannes Film Festival.-Cast:* Daniel Olbrychski - Rafal Olbromski* Boguslaw Kierc - Krzysztof Cedro* Piotr Wysocki - Jan Gintult...
[Polish title] translated as Lost army [English title] by Stefan Żeromski
Stefan Zeromski
Stefan Żeromski was a Polish novelist and dramatist. He was called the "conscience of Polish literature". He also wrote under the pen names: Maurycy Zych, Józef Katerla and Stefan Iksmoreż.- Life :...
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 osteolathyrismOsteolathyrism
Osteolathyrism is a collagen cross-linking deficiency brought on by dietary over-reliance on the seeds of Lathyrus sativus. It is commonly seen in combination with neurolathyrism and angiolathyrism in impoverished areas where famine demands reliance on a crop with known detrimental effects...
, 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
Aortic dissection
Aortic dissection occurs when a tear in the inner wall of the aorta causes blood to flow between the layers of the wall of the aorta and force the layers apart. The dissection typically extends anterograde, but can extend retrograde from the site of the intimal tear. Aortic dissection is a medical...
, exostoses, and kyphoscoliosis
Ehlers-Danlos syndrome
Ehlers–Danlos syndrome is a group of inherited connective tissue disorders, caused by a defect in the synthesis of collagen . The collagen in connective tissue helps tissues to resist deformation...
and other skeletal deformities, apparently as the result of defective aging of collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
tissue
Connective tissue
"Connective tissue" is a fibrous tissue. It is one of the four traditional classes of tissues . Connective Tissue is found throughout the body.In fact the whole framework of the skeleton and the different specialized connective tissues from the crown of the head to the toes determine the form of...
. The cause of this disease is attributed to beta-aminopropionitrile, which inhibits the copper-containing enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
lysyl oxidase
Lysyl oxidase
Lysyl oxidase also known as protein-lysine 6-oxidase is a protein that, in humans, is encoded by the LOX gene. Its inhibition can cause lathyrism, but, at the same time, its upregulation by tumor cells may promote metastasis of the existing tumor, causing it to become malignant and cancerous.-...
, responsible for cross-linking procollagen and proelastin. BAPN is also a metabolic product of a compound present in sprouts of grasspea, pea and lentils.