Neurolathyrism, is a

neurological disease Neurological disorders represent a complex array of medical conditions that fundamentally disrupt the functioning of the nervous system. These disorders affect the brain, spinal cord, and nerve networks, presenting unique diagnosis, treatment, and ...

of humans, caused by eating certain

legumes Legumes are plants in the pea family Fabaceae (or Leguminosae), or the fruit or seeds of such plants. When used as a dry grain for human consumption, the seeds are also called pulses. Legumes are grown agriculturally, primarily for human consu ...

of the

genus Genus (; : genera ) is a taxonomic rank above species and below family (taxonomy), family as used in the biological classification of extant taxon, living and fossil organisms as well as Virus classification#ICTV classification, viruses. In bino ...

Lathyrus ''Lathyrus'' is a genus of flowering plants in the legume family Fabaceae, and contains approximately 160 species. Commonly known as peavines or vetchlings, they are native to temperate areas, with a breakdown of 52 species in Europe, 30 specie ...

''. This disease is mainly associated with the consumption of ''

Lathyrus sativus ''Lathyrus sativus'', also known as grass pea, cicerchia, blue sweet pea, chickling pea, chickling vetch, Indian pea, white pea and white vetch, is a legume (family Fabaceae) commonly grown for human consumption and livestock feed in Asia and Eas ...

'' (also known as ''grass pea'', ''chickling pea'', ''kesari dal'', or ''almorta'') and to a lesser degree with ''

Lathyrus cicera ''Lathyrus cicera'' is a species of wild pea known by the common names red pea, red vetchling 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 h ...

'', ''

Lathyrus ochrus ''Lathyrus ochrus'', the Cyprus vetch, is a species of annual herb in the family Fabaceae. They are climbers and have compound, broad leaves. Flowers are visited by Old World swallowtails and ''Oxythyrea funesta''. Sources References {{Ta ...

'' and ''

Lathyrus clymenum ''Lathyrus clymenum'', also called Spanish vetchling, is a flowering plant in the family Fabaceae, native to the Mediterranean. The seeds are used to prepare a Greek dish called fava santorinis. The plant is cultivated on the island of Santorin ...

'' containing the

toxin A toxin is a naturally occurring poison produced by metabolic activities of living cells or organisms. They occur especially as proteins, often conjugated. The term was first used by organic chemist Ludwig Brieger (1849–1919), derived ...

ODAP Oxalyldiaminopropionic acid (ODAP) is a structural analogue of the neurotransmitter glutamate found in the grass pea ''Lathyrus sativus''. It is the neurotoxin responsible for the motor neuron degeneration syndrome lathyrism. Sources ODAP is foun ...

. This is not to be confused with

osteolathyrism Osteolathyrism, sometimes referred to as odoratism, is a form of the disease Lathyrism. The disease results from the ingestion of ''Lathyrus odoratus'' seeds (sweet peas). The toxin found in the sweet peas is ( beta-aminopropionitrile), which af ...

, a different type of lathyrism that affects the connective tissues. Osteolathyrism results from the ingestion of ''

Lathyrus odoratus The sweet pea, ''Lathyrus odoratus'', is a flowering plant in the genus ''Lathyrus'' in the family Fabaceae (legumes), native to Sicily, southern Italy and the Aegean Islands. It is an annual climbing plant, growing to a height of , where suit ...

'' seeds (''sweet peas'') and is often referred to as odoratism. It is caused by a different toxin (

beta-aminopropionitrile Aminopropionitrile, also known as β-aminopropionitrile (BAPN), is an organic compound with both amine and nitrile functional groups. It is a colourless liquid. The compound occurs naturally and is of interest in the biomedical community. Biochemi ...

) which affects the linking of

collagen Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...

, a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

connective tissue Connective tissue is one of the four primary types of animal tissue, a group of cells that are similar in structure, along with epithelial tissue, muscle tissue, and nervous tissue. It develops mostly from the mesenchyme, derived from the mesod ...

s. Another type of lathyrism is

angiolathyrism Angiolathyrism is a form of lathyrism disease. It is mainly caused the consumption of ''Lathyrus sativus'' (also known as ''grass pea'') and to a lesser degree by ''Lathyrus cicera'', '' Lathyrus ochrus'' and ''Lathyrus clymenum''glutamate Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that ...

analogue 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 The pyramidal tracts include both the corticobulbar tract and the corticospinal tract. These are aggregations of efferent nerve fibers from the upper motor neurons that travel from the cerebral cortex and terminate either in the brainstem (''cort ...

, producing signs of

upper motor neuron Upper motor neurons (UMNs) is a term introduced by William Gowers in 1886. They are found in the cerebral cortex and brainstem and carry information down to activate interneurons and lower motor neurons, which in turn directly signal muscles ...

damage. The toxin may also cause

aortic aneurysm An aortic aneurysm is an enlargement (dilatation) of the aorta to greater than 1.5 times normal size. Typically, there are no symptoms except when the aneurysm dissects or ruptures, which causes sudden, severe pain in the abdomen and lower back ...

. A unique symptom of lathyrism is the

atrophy Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations (which can destroy the gene to build up the organ), malnutrition, poor nourishment, poor circulatory system, circulation, loss of hormone, ...

of gluteal (buttocks) muscles. ODAP is a poison of the

mitochondria A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...

, leading to excess

cell death Cell death is the event of a biological cell ceasing to carry out its functions. This may be the result of the natural process of old cells dying and being replaced by new ones, as in programmed cell death, or may result from factors such as di ...

, especially in

motor neurons A motor neuron (or motoneuron), also known as efferent neuron is a neuron whose cell body is located in the motor cortex, brainstem or the spinal cord, and whose axon (fiber) projects to the spinal cord or outside of the spinal cord to directly or ...

. Children can additionally develop bone deformity and reduced

brain development The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head ( cephalization), usually near organs for special sens ...

Related conditions

A related disease has been identified and named

, because it affects the bones and connecting tissues, instead of the nervous system. It is a skeletal disorder, caused by the toxin

(BAPN), and characterized by

hernias A hernia (: hernias or herniae, from Latin, meaning 'rupture') is the abnormal exit of tissue or an organ, such as the bowel, through the wall of the cavity in which it normally resides. The term is also used for the normal development of the i ...

aortic dissection Aortic dissection (AD) occurs when an injury to the innermost layer of the aorta allows blood to flow between the layers of the aortic wall, forcing the layers apart. In most cases, this is associated with a sudden onset of agonizing ches ...

exostoses An exostosis, also known as a osteochondroma, is a benign chondrogenic lesions derived from aberrant cartilage from the perichondral ring. Exostoses can cause chronic pain ranging from mild to moderate, but rarely severe, depending on the shape, s ...

, and

kyphoscoliosis Kyphoscoliosis describes an abnormal curvature of the spine in both the coronal and sagittal planes. It is a combination of kyphosis and scoliosis. This musculoskeletal disorder often leads to other issues in patients, such as under-ventilatio ...

and other skeletal deformities, apparently as the result of defective aging of

tissue. The cause of this disease is attributed to beta-aminopropionitrile, which inhibits the copper-containing

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

lysyl oxidase Lysyl oxidase (LOX), also known as protein-lysine 6-oxidase, is an enzyme that, in humans, is encoded by the ''LOX'' gene. It catalyzes the conversion of lysine residues into its aldehyde derivative allysine. Allysine form cross-links in extr ...

, responsible for cross-linking procollagen and proelastin. BAPN is also a

metabolic product In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

of a compound present in sprouts of grasspea, pea and lentils. Disorders that are clinically similar are

konzo Konzo is an epidemic paralytic disease occurring among hunger-stricken rural populations in Africa where a diet dominated by insufficiently processed cassava results in simultaneous malnutrition and high dietary cyanide intake. Konzo was first ...

and

lytico-bodig disease Lytico-Bodig (also Lytigo-bodig) disease, Guam disease, amyotrophic lateral sclerosis-parkinsonism-dementia complex (ALS-PDC), and Western Pacific amyotrophic lateral sclerosis-parkinsonism-dementia complex is a rare, terminal neurodegenerative dis ...

Causes

The toxicological cause of the disease has been attributed to the

neurotoxin Neurotoxins are toxins that are destructive to nervous tissue, nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insult (medical), insultsSpencer 2000 that can adversely affect function ...

which acts as a structural analogue of the

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

glutamate Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that ...

. Lathyrism can also be caused by deliberate food

adulteration An adulterant is a substance secretly added to another that may compromise the safety or effectiveness. Typical substances that are adulterated include food, cosmetics, pharmaceuticals or fuels. Definition Adulteration is the practice of secre ...

Association with famine

Ingestion of legumes containing the toxin occurs despite an awareness of the means to detoxify Lathyrus. Drought conditions can lead to shortages of both fuel and water, preventing the necessary detoxification steps from being taken, particularly in impoverished countries. Lathyrism usually occurs where the combination of

poverty Poverty is a state or condition in which an individual lacks the financial resources and essentials for a basic standard of living. Poverty can have diverse Biophysical environmen ...

and

food insecurity Food security is the state of having reliable access to a sufficient quantity of affordable, healthy food. The availability of food for people of any class, gender, ethnicity, or religion is another element of food protection. Similarly, househo ...

leaves few other food options.

Diagnosis

There are no diagnostic criteria for neurolathyrism. Diagnosis is based on clinical features and exclusion of other diagnoses.

Prevention

Eating the chickling pea with legumes having high concentrations of sulphur-based

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

s reduces the risk of lathyrism if such 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 Lactic acid is an organic acid. It has the molecular formula C3H6O3. It is white in the solid state and it is miscible with water. When in the dissolved state, it forms a colorless solution. Production includes both artificial synthesis as wel ...

) and fungal (

tempeh Tempe or tempeh (; , ) is a traditional Indonesian food made from fermented soybeans. It is made by a natural culturing and controlled fermentation process that binds soybeans into a cake form. A fungus, '' Rhizopus oligosporus'' or '' Rhizopu ...

) fermentation is useful to reduce ODAP content. Moist heat (

boiling Boiling or ebullition is the rapid phase transition from liquid to gas or vapor, vapour; the reverse of boiling is condensation. Boiling occurs when a liquid is heated to its boiling point, so that the vapour pressure of the liquid is equal to ...

steaming Steaming is a method of cooking using steam. This is often done with a food steamer, a kitchen appliance made specifically to cook food with steam, but food can also be steamed in a wok. In the American Southwest, steam pits used for cooking ha ...

) denatures protease inhibitors which otherwise add to the toxic effect of raw chickling pea through depletion of protective

sulfur amino acid Sulfur amino acid, sulfur-containing amino acid, or SAA is an amino acid containing element sulfur. Common sulfur amino acids include: * Proteinogenic amino acids ** Cysteine (Cys, C) ** Methionine (Met or M), an essential amino acid in humans * M ...

s. During drought and famine, water for steeping and fuel for boiling are often also in short supply. Poor people sometimes know how to reduce the chance of developing lathyrism but face a choice between

starvation Starvation is a severe deficiency in caloric energy intake, below the level needed to maintain an organism's life. It is the most extreme form of malnutrition. In humans, prolonged starvation can cause permanent organ damage and eventually, de ...

and risking lathyrism.

Epidemiology

This disease is prevalent in some areas of

Bangladesh Bangladesh, officially the People's Republic of Bangladesh, is a country in South Asia. It is the List of countries and dependencies by population, eighth-most populous country in the world and among the List of countries and dependencies by ...

Ethiopia Ethiopia, officially the Federal Democratic Republic of Ethiopia, is a landlocked country located in the Horn of Africa region of East Africa. It shares borders with Eritrea to the north, Djibouti to the northeast, Somalia to the east, Ken ...

India India, officially the Republic of India, is a country in South Asia. It is the List of countries and dependencies by area, seventh-largest country by area; the List of countries by population (United Nations), most populous country since ...

and

Nepal Nepal, officially the Federal Democratic Republic of Nepal, is a landlocked country in South Asia. It is mainly situated in the Himalayas, but also includes parts of the Indo-Gangetic Plain. It borders the Tibet Autonomous Region of China Ch ...

, and affects more men than women. Men between 25 and 40 are particularly vulnerable.

History

The first mentioned intoxication goes back to ancient India and also

Hippocrates Hippocrates of Kos (; ; ), also known as Hippocrates II, was a Greek physician and philosopher of the Classical Greece, classical period who is considered one of the most outstanding figures in the history of medicine. He is traditionally referr ...

mentions a neurological disorder 46 B.C. in Greece caused by Lathyrus seed. During the

Spanish War of Independence The Peninsular War (1808–1814) was fought in the Iberian Peninsula by Kingdom of Portugal, Portugal, Spain and the United Kingdom of Great Britain and Ireland, United Kingdom against the invading and occupying forces of the First French ...

against Napoleon, grasspea served as a famine food. This was the subject of one of

Francisco de Goya Francisco José de Goya y Lucientes (; ; 30 March 1746 – 16 April 1828) was a Spanish romantic painter and printmaker. He is considered the most important Spanish artist of the late 18th and early 19th centuries. His paintings, drawings, a ...

'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 The Vapniarka concentration camp was a Romania, Romanian-administered concentration camp established in occupied Transnistria Governorate in Vapniarka, Ukraine during the Second World War. History Soon after Romania, under the leadership of I ...

in Transnistria, the detainees - most of them Jews - were fed nearly exclusively with fodder pea. Consequently, they became ill from lathyrism.

Modern occurrence

During the post Civil 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 β-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.

References

External links

*
Detection of Toxic Lathyrus sativus flour in Gram Flour
{{Poisoning and toxicity Toxic effect of noxious substances eaten as food Lathyrus Chris McCandless