Osteolathyrism, sometimes referred to as odoratism, is a form of the disease

Lathyrism Lathyrism is a condition caused by eating certain legumes of the genus ''Lathyrus''. There are three types of lathyrism: ''neurolathyrism'', ''osteolathyrism'', and ''angiolathyrism'', all of which are incurable, differing in their symptoms and ...

. The disease 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 suita ...

'' seeds (sweet peas). The

toxin A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849– ...

found in the sweet peas is (

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. Biochem ...

), which affects the linking of

collagen Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...

, a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

connective tissue Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tiss ...

s. The condition results in damage to

bone A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...

and mesenchymal connective tissues. Osteolathyrism occurs in people in combination with

neurolathyrism Neurolathyrism, is a neurological disease of humans, caused by eating certain legumes of the genus ''Lathyrus''. This disease is mainly associated with the consumption of '' Lathyrus sativus'' (also known as ''grass pea'', ''chickling pea'', ''ke ...

and

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''famine A famine is a widespread scarcity of food, caused by several factors including war, natural disasters, crop failure, Demographic trap, population imbalance, widespread poverty, an Financial crisis, economic catastrophe or government policies. Th ...

demands reliance on a

crop A crop is a plant that can be grown and harvested extensively for profit or subsistence. When the plants of the same kind are cultivated at one place on a large scale, it is called a crop. Most crops are cultivated in agriculture or hydroponic ...

with known detrimental effects. It occurs in

cattle Cattle (''Bos taurus'') are large, domesticated, cloven-hooved, herbivores. They are a prominent modern member of the subfamily Bovinae and the most widespread species of the genus ''Bos''. Adult females are referred to as cows and adult mal ...

and

horse The horse (''Equus ferus caballus'') is a domesticated, one-toed, hoofed mammal. It belongs to the taxonomic family Equidae and is one of two extant subspecies of ''Equus ferus''. The horse has evolved over the past 45 to 55 million y ...

s with diets overreliant upon the grass pea. Prominent symptoms include skeletal deformities and bone pain.

Signs and symptoms

*Bone pain *Skeletal deformity *Fatigue *Malnourishment

Cause

Aside from ''L. odoratus'', other members of the genus are also known to cause the disease, including '' L. sylvestris'', '' L. cicera'', and '' L. clymenum''. ''L. odoratus'' grows well under famine conditions, often severe drought, where it is cultivated. These legumes carry a variety of osteolathyrogenic compounds, specifically excitatory amino-compounds. The most widely studied of these compounds is

(BAPN), which exerts its deleterious effect by an unknown yet potently irreversible mechanism. Other instigators are

ureide Acylureas (also called ''N''-acylureas or ureides) are a class of chemical compounds formally derived from the acylation of urea. Uses Insecticides A subclass of acylureas known as benzoylureas are insecticides. They act as insect growth regula ...

semicarbazide Semicarbazide is the chemical compound with the formula OC(NH2)(N2H3). It is a water-soluble white solid. It is a derivative of urea. Synthesis The compound prepared by treating urea with hydrazine:Jean-Pierre Schirmann, Paul Bourdauducq "Hydrazi ...

s and

thiosemicarbazide Thiosemicarbazide is the chemical compound with the formula H2NC(S)NHNH2. A white, odorless solid, it is related to thiourea (H2NC(S)NH2) by the insertion of an NH center. They are commonly used as ligands for transition metals. Many thiosemicar ...

s, which are believed to

chelate Chelation is a type of bonding of ions and molecules to metal ions. It involves the formation or presence of two or more separate coordinate bonds between a polydentate (multiple bonded) ligand and a single central metal atom. These ligands are ...

the prosthetic Cu(II)-

bipyridine Bipyridines also known as bipyridyls, dipyridyls, and dipyridines, are a family of chemical compounds with the formula (C5H4N)2, consisting of two pyridyl (C5H4N) rings. Pyridine is an aromatic nitrogen-containing heterocycle. Bipyridines are of sig ...

cofactor complex in the

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

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 molecules into highly reactive aldehydes that form cross-links in extracellular matri ...

. Lysyl oxidase is an important enzyme for the creation of crosslinks between

triple-helices in

. By

oxidizing Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...

the terminal

amino group In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent such a ...

lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −C ...

, an

aldehyde In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl grou ...

is created. This aldehyde can undergo several reactions with neighboring aldehydes or

amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituen ...

s to create strong

covalent A covalent bond is a chemical bond that involves the sharing of electrons to form electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs. The stable balance of attractive and repulsive forces between atoms ...

cross-links between collagen

tertiary structure Protein tertiary structure is the three dimensional shape of a protein. The tertiary structure will have a single polypeptide chain "backbone" with one or more protein secondary structures, the protein domains. Amino acid side chains may int ...

s in

and

cartilage Cartilage is a resilient and smooth type of connective tissue. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck an ...

. The main product of these reactions is the

aldimine In organic chemistry, an imine ( or ) is a functional group or organic compound containing a carbon–nitrogen double bond (). The nitrogen atom can be attached to a hydrogen or an organic group (R). The carbon atom has two additional single bon ...

compound dehydrohydroxylysinonorleucine. This unique crosslink can be formed by the

Schiff base In organic chemistry, a Schiff base (named after Hugo Schiff) is a compound with the general structure ( = alkyl or aryl, but not hydrogen). They can be considered a sub-class of imines, being either secondary ketimines or secondary aldimine ...

mechanism in which the lone pair of

electron The electron ( or ) is a subatomic particle with a negative one elementary electric charge. Electrons belong to the first generation of the lepton particle family, and are generally thought to be elementary particles because they have no kn ...

s on a

primary amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent such a ...

react with the

carbonyl In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containing a ...

carbon of an aldehyde. Other crosslinks include the formation of an α,β- unsaturated

ketone In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bo ...

via

aldol condensation An aldol condensation is a condensation reaction in organic chemistry in which two carbonyl moieties (of aldehydes or ketones) react to form a β-hydroxyaldehyde or β-hydroxyketone (an aldol reaction), and this is then followed by dehydration to ...

and hydroxylysinonorleucine. If these crosslinks are not formed, as in the case of osteolathyrism, the synthesis of strong

mesenchymal Mesenchyme () is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood or bone. The interactions between mesenchyme and epithelium help to form nearly every o ...

and

mesodermal The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical Embry ...

tissue is inhibited. Symptoms of osteolathyrism include weakness and fragility of connective tissue (i.e., skin, bones, and blood vessels (

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''paralysis Paralysis (also known as plegia) is a loss of motor function in one or more muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory damage. In the United States, roughly 1 in 50 ...

of the lower extremities associated with neurolathyrism. For these reasons, compounds containing lathyrogens should be avoided during

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

and growth of a

child A child ( : children) is a human being between the stages of birth and puberty, or between the developmental period of infancy and puberty. The legal definition of ''child'' generally refers to a minor, otherwise known as a person younger ...

Prevention

Prevention of osteolathyrism can be achieved with a cessation of ''L. sativus'' consumption.

References

External links

{{Medical resources , ICD10 = , ICD9 = , ICDO = , OMIM = , DiseasesDB = , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , MeSH = , GeneReviewsNBK = , GeneReviewsName = , Orphanet = Structural proteins Toxic effect of noxious substances eaten as food