Lathyrism - dismech

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Mappings

MONDO

MONDO:0043339 lathyrism

Primary MONDO disease identifier for this lathyrism entry.

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Definitions

1

Clinical case definition of neurolathyrism

Neurolathyrism is defined as an upper motor neuron disorder presenting with spastic paraparesis of the lower limbs and sensory sparing, caused by prolonged over-consumption of grass pea (Lathyrus sativus) containing the neurotoxin beta-ODAP.

CASE_DEFINITION Disease-level clinical case definition for the neurolathyrism subtype.

Show evidence (1 reference)

PMID:37798732 SUPPORT Human Clinical

"Neurolathyrism is an upper motor neuron disorder characterized by"

Community studies define neurolathyrism by upper-motor-neuron spastic paraparesis caused by grass pea over-consumption.

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Subtypes

2

Neurolathyrism

The principal human form, caused by chronic dietary exposure to the excitotoxic amino acid beta-ODAP in grass pea (Lathyrus sativus). Produces a permanent spastic paraparesis from selective degeneration of upper motor neurons and the corticospinal tracts, with characteristic sparing of sensory systems. Onset is typically abrupt, often after a period of heavy grass pea consumption during famine, and predominantly affects males aged 15-30. Disability is clinically graded in stages (I-IV), from walking-stick dependence to a bedridden, contracted state.

Connective Tissue Lathyrism (Osteolathyrism / Angiolathyrism)

A connective-tissue group of forms caused by the nitrile beta-aminopropionitrile (BAPN) from sweet pea (Lathyrus odoratus). BAPN irreversibly inhibits lysyl oxidase, blocking cross-linking of collagen and elastin and producing skeletal deformities and exostoses (osteolathyrism) and, in its vascular variant (angiolathyrism), aortic aneurysm, dissection, and rupture. Best characterized in animal models and used experimentally; spontaneous human disease is rare and chiefly historical or reported in isolated cases.

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Pathophysiology

9

Beta-ODAP Excitatory Amino Acid Receptor Agonism

Beta-ODAP is a structural analog of L-glutamate that acts as an agonist at AMPA-type ionotropic glutamate receptors on motor neurons. This is the initiating molecular event of neurolathyrism: an exogenous dietary excitotoxin engaging glutamatergic signaling in the absence of any genetic lesion.

upper motor neuron CL:0008048

glutamate receptor signaling pathway GO:0007215 ↑ INCREASED

Downstream

TRP Channel and Group I mGluR Calcium Entry AMPA agonism is accompanied by voltage-independent calcium entry routes unique to beta-ODAP.

Motor Neuron Calcium Overload Receptor activation drives sustained intracellular calcium accumulation.

Show evidence (1 reference)

PMID:24582715 SUPPORT In Vitro

"β-N-oxalyl-L-α,β-diaminopropionic acid (L-β-ODAP), an AMPA receptor agonist"

Identifies beta-ODAP as an AMPA-type glutamate receptor agonist, the initiating excitotoxic event.

TRP Channel and Group I mGluR Calcium Entry

Beyond classical AMPA-receptor activation, beta-ODAP elicits a prolonged, voltage-independent rise in intracellular calcium mediated by transient receptor potential (TRP) channels and group I metabotropic glutamate receptors. This TRP/mGluR-dependent calcium entry is a distinguishing feature of beta-ODAP toxicity relative to conventional AMPA agonists and sustains the calcium load that injures motor neurons.

motor neuron CL:0000100

calcium ion import GO:0070509 ↑ INCREASED

Downstream

Motor Neuron Calcium Overload TRP/mGluR-mediated entry adds to the sustained calcium burden.

Show evidence (1 reference)

PMID:24582715 SUPPORT In Vitro

"The results show the involvement of TRPs and mGluR I"

Primary rat motor neuron cultures implicate TRP channels and group I mGluR in beta-ODAP-induced calcium mobilization and toxicity.

Motor Neuron Calcium Overload

Convergent calcium entry through AMPA receptors, TRP channels, and group I mGluR produces a prolonged elevation of intracellular calcium in spinal motor neurons. The magnitude of calcium accumulation is inversely related to motor-neuron survival, making calcium overload the proximate driver of excitotoxic injury.

motor neuron CL:0000100

cytosolic calcium ion homeostasis GO:0051480 ⚠ ABNORMAL

Downstream

Mitochondrial Dysfunction and Oxidative Stress Calcium overload disrupts mitochondrial function and generates reactive oxygen species.

Show evidence (1 reference)

PMID:24582715 SUPPORT In Vitro

"L-β-ODAP caused a prolonged rise of intracellular Ca(2+)"

Demonstrates sustained intracellular calcium elevation in motor neurons as the proximate excitotoxic event.

Mitochondrial Dysfunction and Oxidative Stress

Calcium overload contributes to mitochondrial dysfunction and reactive-oxygen-species generation. Proteomic and cellular studies of beta-ODAP exposure show early upregulation of free-radical-scavenging and oxidative-stress proteins and altered mitochondrial membrane potential; in some models these changes are transient and non-lethal, indicating oxidative stress acts alongside excitotoxic calcium injury rather than as a sole effector of motor-neuron degeneration.

motor neuron CL:0000100

response to oxidative stress GO:0006979 ↑ INCREASED

Downstream

Upper Motor Neuron and Corticospinal Tract Degeneration Sustained excitotoxic and oxidative injury culminates in degeneration of upper motor neurons.

Show evidence (1 reference)

PMID:30057701 PARTIAL Model Organism

"free radical scavenging, oxidative stress and neurodegenerative disorders were initially up-regulated"

Chick brain proteomics after beta-ODAP shows early induction of oxidative-stress and neurodegeneration-associated proteins; the study emphasizes these changes can be transient, so it partially supports oxidative stress as a contributing (not sole) effector.

Upper Motor Neuron and Corticospinal Tract Degeneration

Excitotoxic calcium injury and oxidative stress drive degeneration of upper motor neurons, including the large Betz cells of the motor cortex, and their corticospinal (pyramidal) axons, with relative sparing of lower motor neurons and sensory pathways. The resulting upper motor neuron syndrome manifests as spastic paraparesis. In rat models of neurolathyrism, motor neurons are depleted in lumbosacral spinal segments. Once established, the deficit is permanent.

Betz cell CL:0008049 pyramidal neuron CL:0000598

neuron apoptotic process GO:0051402 ↑ INCREASED

Show evidence (2 references)

PMID:41965594 SUPPORT Human Clinical

"Neurolathyrism is an upper motor neuron disorder affecting the corticospinal tracts and causing spastic paraparesis"

Community clinical study characterizes neurolathyrism as an upper motor neuron / corticospinal tract disorder producing spastic paraparesis.

PMID:30930396 SUPPORT Model Organism

"MNs of these rats were greatly decreased at their"

A rat model of neurolathyrism shows motor-neuron depletion in lumbosacral segments, supporting motor-neuron degeneration.

BAPN Inhibition of Lysyl Oxidase

In the connective-tissue forms, the nitrile toxin beta-aminopropionitrile (BAPN) irreversibly inhibits lysyl oxidase (LOX), the copper-dependent oxido-deaminase that initiates covalent cross-linking of collagen and elastin by oxidatively deaminating lysine and hydroxylysine residues. LOX inhibition is the initiating molecular lesion of osteolathyrism and angiolathyrism.

fibroblast CL:0000057

peptidyl-lysine oxidation GO:0018057 ↓ DECREASED

Downstream

Collagen and Elastin Cross-link Failure Loss of LOX activity prevents covalent cross-linking of the extracellular matrix.

Show evidence (2 references)

PMID:33462684 SUPPORT Model Organism

"LOX activity can be irreversibly inhibited by the administration of"

Establishes BAPN as an irreversible inhibitor of lysyl oxidase, the initiating lesion of connective-tissue lathyrism.

PMID:25979340 SUPPORT In Vitro

"modify the side chain of lysyl residues in collagen and elastin"

Defines the lysyl oxidase reaction on collagen and elastin that BAPN blocks.

Collagen and Elastin Cross-link Failure

Without lysyl oxidase activity, collagen and elastin fail to form the non-reducible aldehyde-derived intermolecular cross-links required for tensile strength and proper fibril architecture. The extracellular matrix is mechanically weak and structurally abnormal, predisposing connective tissues throughout the body to failure.

fibroblast CL:0000057

collagen fibril organization GO:0030199 ⚠ ABNORMAL extracellular matrix organization GO:0030198 ⚠ ABNORMAL

Downstream

Skeletal Connective Tissue Weakening (Osteolathyrism) Weak collagen impairs bone matrix quality and skeletal integrity.

Aortic Wall Disruption with TGF-beta and MMP Upregulation (Angiolathyrism) Defective elastin/collagen cross-linking weakens the aortic wall.

Show evidence (1 reference)

PMID:25979340 SUPPORT In Vitro

"the formation of aldimine-derived cross-links in collagen, and the constructs"

BAPN inhibition of LOX blocks collagen cross-link formation and yields mechanically weak, structurally abnormal matrix.

Skeletal Connective Tissue Weakening (Osteolathyrism)

Defective collagen cross-linking degrades bone matrix quality and skeletal connective tissue, producing the skeletal deformities and periosteal/exostotic lesions of osteolathyrism. In a porcine BAPN model, osteolathyrism with skeletal changes arose as an unexpected systemic effect of lysyl oxidase inhibition.

osteoblast CL:0000062

extracellular matrix organization GO:0030198 ⚠ ABNORMAL

Show evidence (1 reference)

PMID:40545783 SUPPORT Model Organism

"CT characteristics of osteolathyrism as an unexpected adverse event in both pigs"

BAPN administration in pigs produced osteolathyrism with skeletal changes detectable on CT.

Aortic Wall Disruption with TGF-beta and MMP Upregulation (Angiolathyrism)

In angiolathyrism, defective elastin and collagen cross-linking weakens the aortic media. In rat models, lysyl oxidase inhibition by BAPN disrupts the ascending aortic wall and is accompanied by increased apoptosis, enhanced TGF-beta/SMAD2 signaling, and upregulation of matrix metalloproteinases MMP-2 and MMP-9 — a secondary remodeling cascade shared with heritable aortopathies — culminating in aneurysm, dissection, and rupture. This node conforms to the conserved aortopathy TGF-beta dysregulation hub, with BAPN-induced lysyl oxidase inhibition substituting for the heritable primary lesions (FBN1/TGFBR/SMAD3, etc.) as the upstream cause.

vascular smooth muscle cell CL:0000359

transforming growth factor beta receptor signaling pathway GO:0007179 ↑ INCREASED extracellular matrix disassembly GO:0022617 ↑ INCREASED

Show evidence (3 references)

PMID:33462684 SUPPORT Model Organism

"stimulated TGF-β signaling (increase of nuclear"

In rats, BAPN-induced LOX inhibition stimulates TGF-beta/SMAD2 signaling contributing to ascending aortic wall disruption.

PMID:33462684 SUPPORT Model Organism

"up-regulated the expression of metalloproteinases-2 and"

MMP-2 and MMP-9 upregulation accompanies LOX inhibition and contributes to aortic wall destruction.

PMID:20547706 SUPPORT Other

"particularly involving the vascular and skeletal systems, especially aortic"

Review of human and animal lathyrism documents vascular and skeletal connective-tissue disruption, especially aortic dissection/rupture.

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Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.

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Phenotypes

12

Cardiovascular 2

Aortic aneurysm Aortic aneurysm HP:0004942

Show evidence (1 reference)

PMID:33462684 SUPPORT Model Organism

"BAPN administration caused disruption of the ascending aortic wall"

BAPN-induced lysyl oxidase inhibition disrupts the ascending aortic wall in rats.

Aortic dissection Aortic dissection HP:0002647

Show evidence (1 reference)

PMID:20547706 SUPPORT Other

"particularly involving the vascular and skeletal systems, especially aortic"

Review documents aortic dissection/rupture as a hallmark of animal lathyrism.

Musculoskeletal 2

Spastic paraplegia Spastic paraplegia HP:0001258

Show evidence (2 references)

PMID:37798732 SUPPORT Human Clinical

"Neurolathyrism is an upper motor neuron disorder characterized by"

Defines neurolathyrism by spastic paraparesis of upper-motor-neuron origin.

PMID:36108319 SUPPORT Human Clinical

"he had spastic paraparesis with brisk deep tendon reflexes and positive Babinski sign with sustained bilateral ankle clonus"

Clinical case documents spastic paraparesis with upper motor neuron signs.

Skeletal dysplasia Skeletal dysplasia HP:0002652

Show evidence (1 reference)

PMID:40545783 SUPPORT Model Organism

"CT characteristics of osteolathyrism as an unexpected adverse event in both pigs"

Porcine BAPN exposure produced osteolathyrism with skeletal changes on CT.

Nervous System 1

Depression FREQUENT Depression HP:0000716

Show evidence (1 reference)

PMID:38627754 SUPPORT Human Clinical

"the prevalence of MDD was found to be 38.7%"

Community study found major depressive disorder in 38.7% of adult neurolathyrism patients.

Other 7

Lower limb spasticity Lower limb spasticity HP:0002061

Show evidence (1 reference)

PMID:9577009 SUPPORT Human Clinical

"spastic muscle tone in the abductors, stiffness of Achilles and"

Randomized trial in neurolathyrism objectively measured spastic lower-limb muscle tone.

Lower limb hyperreflexia Lower limb hyperreflexia HP:0002395

Show evidence (1 reference)

PMID:36108319 SUPPORT Human Clinical

"he had spastic paraparesis with brisk deep tendon reflexes and positive Babinski sign with sustained bilateral ankle clonus"

Brisk deep tendon reflexes documented on examination, indicating lower-limb hyperreflexia.

Babinski sign Babinski sign HP:0003487

Show evidence (1 reference)

PMID:36108319 SUPPORT Human Clinical

"positive Babinski sign with sustained bilateral ankle clonus"

Positive Babinski sign documented on examination, a cardinal corticospinal sign.

Clonus Clonus HP:0002169

Show evidence (2 references)

PMID:36108319 SUPPORT Human Clinical

"sustained bilateral ankle clonus"

Sustained bilateral ankle clonus documented on examination.

PMID:9577009 SUPPORT Human Clinical

"spastic muscle tone in the abductors, stiffness of Achilles and"

The same trial recorded spontaneous ankle clonus as an objective spasticity measure reduced by treatment.

Spastic gait Spastic gait HP:0002064

Show evidence (1 reference)

PMID:36108319 SUPPORT Human Clinical

"a gradual decline in the power in the bilateral lower limbs, both in extension and flexion"

Progressive lower-limb motor decline leading to inability to walk, consistent with spastic gait.

Lower limb muscle weakness Lower limb muscle weakness HP:0007340

Show evidence (1 reference)

PMID:36108319 SUPPORT Human Clinical

"a gradual decline in the power in the bilateral lower limbs, both in extension and flexion"

Documents progressive bilateral lower-limb weakness.

Exostoses Exostoses HP:0100777

Show evidence (1 reference)

PMID:36108319 PARTIAL Human Clinical

"bony exostosis, which have never been reported in"

A single human case reports bony exostosis with neurolathyrism, proposed as a new osteolathyrism-like form; isolated finding.

💊

Medical Actions

5

Toxin Reduction by Food Processing

Action: dietary intervention MAXO:0000088

Soaking, boiling and decanting, fermentation, or roasting grass pea substantially lowers beta-ODAP content and is a principal preventive measure where the crop remains a dietary staple.

Show evidence (1 reference)

PMID:39329978 SUPPORT Other

"traditional ways to reduce β-ODAP"

Review describes traditional food-processing methods that reduce beta-ODAP content.

Dietary Diversification and Low-ODAP Cultivars

Action: dietary intervention MAXO:0000088

Diet: restrict grass pea FOODON:00003735

Public-health prevention through dietary diversification, avoidance of exclusive grass pea reliance, and development of low-ODAP cultivars by classical breeding and, more recently, proposed gene-editing of the beta-ODAP biosynthetic pathway. Improving the low methionine/cysteine content of grass pea is a parallel nutritional goal.

Show evidence (1 reference)

PMID:39329978 SUPPORT Other

"some varieties with low β-ODAP have been developed through classical breeding"

Low-beta-ODAP grass pea cultivars have been developed to reduce neurolathyrism risk.

Antispasticity Pharmacotherapy

Action: Pharmacotherapy NCIT:C15986

Agent: tolperisone CHEBI:32244

Symptomatic treatment of spasticity. A randomized, double-blind, placebo-controlled trial showed the centrally acting muscle relaxant tolperisone improved spastic muscle tone, ankle clonus, and walking in neurolathyrism; other muscle relaxants such as baclofen are used clinically. The AMPA-receptor antagonist perampanel and gabapentin have been used for neuromuscular pain. Pharmacotherapy is symptomatic and does not reverse the underlying motor-neuron injury.

Show evidence (1 reference)

PMID:9577009 SUPPORT Human Clinical

"tolperisone is a well tolerated and efficacious"

Randomized controlled trial concluded tolperisone is efficacious for symptomatic treatment of neurolathyrism spasticity.

Physical Therapy and Rehabilitation

Action: physical therapy MAXO:0000011

Physiotherapy, stretching, orthoses, and assistive devices to maintain mobility and reduce contractures in established neurolathyrism.

Show evidence (1 reference)

PMID:36108319 SUPPORT Human Clinical

"treatment largely remains supportive"

No specific cure exists; physiotherapy and supportive care are the mainstay of management.

Supportive Care

Action: supportive care MAXO:0000950

There is no disease-modifying therapy for established neurolathyrism; care is supportive, addressing disability, pain, and the high burden of psychosocial comorbidity (including major depressive disorder) through counselling and social support.

Show evidence (1 reference)

PMID:38627754 SUPPORT Human Clinical

"Neurolathyrism is a chronic illness characterized by lifelong incurable spastic"

Neurolathyrism is a lifelong, incurable disability requiring long-term supportive care.

🌍

Environmental Factors

1

Grass pea (Lathyrus sativus) overconsumption

Sustained heavy dietary reliance on grass pea — typically over weeks to months during drought and famine when other crops fail — is the cause of neurolathyrism. Risk rises with feeding only grass pea, high grass-pea-to-cereal mixing ratios, and consumption of immature seeds. Grass pea is drought- and flood-tolerant and protein-rich, making it a famine survival food in parts of South Asia (India, Bangladesh, Nepal) and the Horn of Africa (Ethiopia). Male sex and older age are associated with higher risk.

Show evidence (2 references)

PMID:37798732 SUPPORT Human Clinical

"which is caused by the prolonged over-consumption of grass"

Community study attributes neurolathyrism to prolonged grass pea overconsumption.

PMID:41965594 SUPPORT Human Clinical

"male sex (AOR = 3.57; 95% CI = 1.79-7.10)"

Male sex is a significant risk factor for neurolathyrism.

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Differential Diagnoses

2

Conditions with similar clinical presentations that must be differentiated from Lathyrism:

Konzo (cassavism) Not Yet Curated MONDO:0022666

Overlapping Features Konzo is the closest mimic of neurolathyrism: an epidemic, abrupt-onset, symmetric upper-motor-neuron spastic paraparesis affecting young people during food shortages. It is caused by cyanide from insufficiently processed bitter cassava rather than by grass pea beta-ODAP.

Distinguishing Features

Causative exposure is cyanogenic bitter cassava (Manihot esculenta), not grass pea.
Geographically clustered in sub-Saharan Africa (cassava-dependent regions).
Clinically near-identical upper-motor-neuron spastic paraparesis, so dietary history is the key discriminator.

Show evidence (2 references)

PMID:39608576 SUPPORT Other

"konzo, a tropical spastic paraparesis due to selective upper motor"

Konzo is an upper-motor-neuron spastic paraparesis from cassava-derived cyanide, mimicking neurolathyrism but with a distinct toxin.

PMID:37620067 SUPPORT Other

"excessive consumption of cyanide-containing bitter cassava"

Konzo arises from excessive consumption of cyanide-containing bitter cassava, distinguishing it from grass-pea neurolathyrism.

Tropical spastic paraparesis (HTLV-1 myelopathy) Not Yet Curated MONDO:0008039

Overlapping Features HTLV-1-associated myelopathy / tropical spastic paraparesis produces a chronic spastic paraparesis that can resemble neurolathyrism but is caused by the retrovirus HTLV-1, is serologically diagnosable, and often involves sensory and bladder dysfunction.

Distinguishing Features

Infectious etiology (HTLV-1 retrovirus) confirmable by serology/PCR.
Frequently involves sensory and sphincter disturbance, whereas neurolathyrism characteristically spares sensation.
No history of grass pea consumption.

Show evidence (1 reference)

PMID:37620067 SUPPORT Other

"the retrovirus HTLV-1 is the causeof tropical spastic paraparesis/paraplegia or TSP"

TSP is caused by the retrovirus HTLV-1, distinguishing it from toxin-induced neurolathyrism (quote reproduces a spacing artifact in the source abstract).

{ }

Source YAML

click to show

name: Lathyrism
creation_date: "2026-06-12T00:00:00Z"
description: >-
  Lathyrism is a toxin-mediated environmental disorder caused by excessive consumption
  of, or exposure to, Lathyrus legumes and the toxins they contain. The dominant human
  form, neurolathyrism, is an irreversible upper motor neuron disease producing spastic
  paraparesis of the legs, caused by the excitatory amino acid neurotoxin beta-N-oxalyl-
  L-alpha,beta-diaminopropionic acid (beta-ODAP, also called BOAA), a glutamate analog
  found in grass pea (Lathyrus sativus). The toxic beta-isomer accounts for the bulk of
  ODAP and acts as an agonist at AMPA-type ionotropic glutamate receptors, additionally
  driving voltage-independent calcium entry through TRP channels and group I metabotropic
  glutamate receptors; the resulting motor-neuron calcium overload, mitochondrial
  dysfunction and oxidative stress degenerate upper motor neurons and the corticospinal
  tracts. Neurolathyrism characteristically spares sensory and sphincter function and
  emerges in epidemic form during droughts and famines, when grass pea becomes a dietary
  staple, disproportionately affecting young adult males. A second group of forms,
  osteolathyrism (skeletal) and angiolathyrism (vascular), is produced by the nitrile
  toxin beta-aminopropionitrile (BAPN) from sweet pea (Lathyrus odoratus); BAPN
  irreversibly inhibits the copper-dependent enzyme lysyl oxidase, impairing collagen and
  elastin cross-linking and causing connective-tissue fragility, skeletal deformity, and
  aortic aneurysm/dissection. These connective-tissue forms are documented chiefly in
  animal models and are widely used experimentally. There is no cure for established
  neurolathyrism; management is preventive (detoxification of grass pea, dietary
  diversification, low-ODAP cultivars) and supportive (antispasticity therapy,
  physiotherapy, assistive devices).
category: Environmental
disease_term:
  preferred_term: lathyrism
  term:
    id: MONDO:0043339
    label: lathyrism
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0043339
      label: lathyrism
    mapping_predicate: skos:exactMatch
    mapping_source: MONDO
    mapping_justification: Primary MONDO disease identifier for this lathyrism entry.
synonyms:
- Neurolathyrism
- Osteolathyrism
- Angiolathyrism
- Grass pea poisoning
- Lathyrus sativus poisoning
- BOAA poisoning
parents:
- poisoning
has_subtypes:
- name: Neurolathyrism
  display_name: Neurolathyrism
  description: >-
    The principal human form, caused by chronic dietary exposure to the excitotoxic
    amino acid beta-ODAP in grass pea (Lathyrus sativus). Produces a permanent spastic
    paraparesis from selective degeneration of upper motor neurons and the corticospinal
    tracts, with characteristic sparing of sensory systems. Onset is typically abrupt,
    often after a period of heavy grass pea consumption during famine, and predominantly
    affects males aged 15-30. Disability is clinically graded in stages (I-IV), from
    walking-stick dependence to a bedridden, contracted state.
- name: Connective Tissue Lathyrism
  display_name: Connective Tissue Lathyrism (Osteolathyrism / Angiolathyrism)
  description: >-
    A connective-tissue group of forms caused by the nitrile beta-aminopropionitrile
    (BAPN) from sweet pea (Lathyrus odoratus). BAPN irreversibly inhibits lysyl oxidase,
    blocking cross-linking of collagen and elastin and producing skeletal deformities and
    exostoses (osteolathyrism) and, in its vascular variant (angiolathyrism), aortic
    aneurysm, dissection, and rupture. Best characterized in animal models and used
    experimentally; spontaneous human disease is rare and chiefly historical or reported
    in isolated cases.
prevalence:
- subtype: Neurolathyrism
  population: Adults in Delanta district, Amhara region, Ethiopia (community survey, 2023)
  percentage: 6.6
  notes: >-
    Community-based cross-sectional survey; 56 of 470 participants (11.9%) reported
    neurolathyrism, with an estimated population-level prevalence of 6.6%.
  evidence:
  - reference: PMID:41965594
    reference_title: "Neurolathyrism in Delanta, Ethiopia: prevalence, associated factors, and social impact: a cross-sectional study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "56 (11.9%)"
    explanation: "Of 470 participants surveyed in Delanta, 56 (11.9%) reported neurolathyrism."
- subtype: Neurolathyrism
  population: Grass pea cultivation areas of Dawunt district, north-eastern Ethiopia (2022)
  percentage: 2.4
  notes: >-
    Community-based multilevel study; household-level prevalence 9.2% and population-level
    point prevalence 2.4%.
  evidence:
  - reference: PMID:37798732
    reference_title: "Prevalence of Neurolathyrism and its associated factors in Grass pea cultivation areas of Dawunt District, North-eastern Ethiopia; 2022: a community based multilevel analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "9.2% (7.2-11.7%)"
    explanation: "Household-level neurolathyrism prevalence in Dawunt was 9.2%, with a 2.4% population-level point prevalence."
progression:
- phase: Permanent lifelong disability
  subtype: Neurolathyrism
  notes: >-
    Neurolathyrism produces a permanent, incurable spastic paralysis of the lower
    extremities. Disability is clinically graded in stages (I-IV), from walking-stick
    dependence to a bedridden, contracted state; once established the deficit does not
    remit, though it is non-progressive after grass pea exposure ceases.
  evidence:
  - reference: PMID:38627754
    reference_title: "Prevalence of major depressive disorder and its associated factors among adult patients with neurolathyrism in Dawunt District, Ethiopia; 2022: community-based cross-sectional study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Neurolathyrism is a chronic illness characterized by lifelong incurable spastic"
    explanation: "Neurolathyrism is characterized as a chronic illness with lifelong incurable spastic paralysis of the lower extremities."
pathophysiology:
- name: Beta-ODAP Excitatory Amino Acid Receptor Agonism
  description: >-
    Beta-ODAP is a structural analog of L-glutamate that acts as an agonist at AMPA-type
    ionotropic glutamate receptors on motor neurons. This is the initiating molecular
    event of neurolathyrism: an exogenous dietary excitotoxin engaging glutamatergic
    signaling in the absence of any genetic lesion.
  chemical_entities:
  - preferred_term: beta-ODAP
    term:
      id: CHEBI:16399
      label: N(3)-oxalyl-L-2,3-diaminopropionic acid
  cell_types:
  - preferred_term: upper motor neuron
    term:
      id: CL:0008048
      label: upper motor neuron
  biological_processes:
  - preferred_term: glutamate receptor signaling pathway
    modifier: INCREASED
    term:
      id: GO:0007215
      label: glutamate receptor signaling pathway
  evidence:
  - reference: PMID:24582715
    reference_title: "New insights into the mechanism of neurolathyrism: L-β-ODAP triggers [Ca2+]i accumulation and cell death in primary motor neurons through transient receptor potential channels and metabotropic glutamate receptors."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "β-N-oxalyl-L-α,β-diaminopropionic acid (L-β-ODAP), an AMPA receptor agonist"
    explanation: "Identifies beta-ODAP as an AMPA-type glutamate receptor agonist, the initiating excitotoxic event."
  downstream:
  - target: TRP Channel and Group I mGluR Calcium Entry
    description: AMPA agonism is accompanied by voltage-independent calcium entry routes unique to beta-ODAP.
  - target: Motor Neuron Calcium Overload
    description: Receptor activation drives sustained intracellular calcium accumulation.
- name: TRP Channel and Group I mGluR Calcium Entry
  description: >-
    Beyond classical AMPA-receptor activation, beta-ODAP elicits a prolonged,
    voltage-independent rise in intracellular calcium mediated by transient receptor
    potential (TRP) channels and group I metabotropic glutamate receptors. This
    TRP/mGluR-dependent calcium entry is a distinguishing feature of beta-ODAP toxicity
    relative to conventional AMPA agonists and sustains the calcium load that injures
    motor neurons.
  cell_types:
  - preferred_term: motor neuron
    term:
      id: CL:0000100
      label: motor neuron
  biological_processes:
  - preferred_term: calcium ion import
    modifier: INCREASED
    term:
      id: GO:0070509
      label: calcium ion import
  evidence:
  - reference: PMID:24582715
    reference_title: "New insights into the mechanism of neurolathyrism: L-β-ODAP triggers [Ca2+]i accumulation and cell death in primary motor neurons through transient receptor potential channels and metabotropic glutamate receptors."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "The results show the involvement of TRPs and mGluR I"
    explanation: "Primary rat motor neuron cultures implicate TRP channels and group I mGluR in beta-ODAP-induced calcium mobilization and toxicity."
  downstream:
  - target: Motor Neuron Calcium Overload
    description: TRP/mGluR-mediated entry adds to the sustained calcium burden.
- name: Motor Neuron Calcium Overload
  description: >-
    Convergent calcium entry through AMPA receptors, TRP channels, and group I mGluR
    produces a prolonged elevation of intracellular calcium in spinal motor neurons. The
    magnitude of calcium accumulation is inversely related to motor-neuron survival,
    making calcium overload the proximate driver of excitotoxic injury.
  cell_types:
  - preferred_term: motor neuron
    term:
      id: CL:0000100
      label: motor neuron
  biological_processes:
  - preferred_term: cytosolic calcium ion homeostasis
    modifier: ABNORMAL
    term:
      id: GO:0051480
      label: regulation of cytosolic calcium ion concentration
  evidence:
  - reference: PMID:24582715
    reference_title: "New insights into the mechanism of neurolathyrism: L-β-ODAP triggers [Ca2+]i accumulation and cell death in primary motor neurons through transient receptor potential channels and metabotropic glutamate receptors."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "L-β-ODAP caused a prolonged rise of intracellular Ca(2+)"
    explanation: "Demonstrates sustained intracellular calcium elevation in motor neurons as the proximate excitotoxic event."
  downstream:
  - target: Mitochondrial Dysfunction and Oxidative Stress
    description: Calcium overload disrupts mitochondrial function and generates reactive oxygen species.
- name: Mitochondrial Dysfunction and Oxidative Stress
  description: >-
    Calcium overload contributes to mitochondrial dysfunction and reactive-oxygen-species
    generation. Proteomic and cellular studies of beta-ODAP exposure show early
    upregulation of free-radical-scavenging and oxidative-stress proteins and altered
    mitochondrial membrane potential; in some models these changes are transient and
    non-lethal, indicating oxidative stress acts alongside excitotoxic calcium injury
    rather than as a sole effector of motor-neuron degeneration.
  cell_types:
  - preferred_term: motor neuron
    term:
      id: CL:0000100
      label: motor neuron
  biological_processes:
  - preferred_term: response to oxidative stress
    modifier: INCREASED
    term:
      id: GO:0006979
      label: response to oxidative stress
  evidence:
  - reference: PMID:30057701
    reference_title: "Proteomic Changes in Chick Brain Proteome Post Treatment with Lathyrus Sativus Neurotoxin, β-N-Oxalyl-L-α,β-Diaminopropionic Acid (L-ODAP): A Better Insight to Transient Neurolathyrism."
    supports: PARTIAL
    evidence_source: MODEL_ORGANISM
    snippet: "free radical scavenging, oxidative stress and neurodegenerative disorders were initially up-regulated"
    explanation: "Chick brain proteomics after beta-ODAP shows early induction of oxidative-stress and neurodegeneration-associated proteins; the study emphasizes these changes can be transient, so it partially supports oxidative stress as a contributing (not sole) effector."
  downstream:
  - target: Upper Motor Neuron and Corticospinal Tract Degeneration
    description: Sustained excitotoxic and oxidative injury culminates in degeneration of upper motor neurons.
- name: Upper Motor Neuron and Corticospinal Tract Degeneration
  description: >-
    Excitotoxic calcium injury and oxidative stress drive degeneration of upper motor
    neurons, including the large Betz cells of the motor cortex, and their corticospinal
    (pyramidal) axons, with relative sparing of lower motor neurons and sensory pathways.
    The resulting upper motor neuron syndrome manifests as spastic paraparesis. In rat
    models of neurolathyrism, motor neurons are depleted in lumbosacral spinal segments.
    Once established, the deficit is permanent.
  cell_types:
  - preferred_term: Betz cell
    term:
      id: CL:0008049
      label: Betz cell
  - preferred_term: pyramidal neuron
    term:
      id: CL:0000598
      label: pyramidal neuron
  biological_processes:
  - preferred_term: neuron apoptotic process
    modifier: INCREASED
    term:
      id: GO:0051402
      label: neuron apoptotic process
  evidence:
  - reference: PMID:41965594
    reference_title: "Neurolathyrism in Delanta, Ethiopia: prevalence, associated factors, and social impact: a cross-sectional study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Neurolathyrism is an upper motor neuron disorder affecting the corticospinal tracts and causing spastic paraparesis"
    explanation: "Community clinical study characterizes neurolathyrism as an upper motor neuron / corticospinal tract disorder producing spastic paraparesis."
  - reference: PMID:30930396
    reference_title: "[Research in Motor Neuron Diseases Caused by Natural Substances: Focus on Pathological Mechanisms of Neurolathyrism]."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "MNs of these rats were greatly decreased at their"
    explanation: "A rat model of neurolathyrism shows motor-neuron depletion in lumbosacral segments, supporting motor-neuron degeneration."
- name: BAPN Inhibition of Lysyl Oxidase
  description: >-
    In the connective-tissue forms, the nitrile toxin beta-aminopropionitrile (BAPN)
    irreversibly inhibits lysyl oxidase (LOX), the copper-dependent oxido-deaminase that
    initiates covalent cross-linking of collagen and elastin by oxidatively deaminating
    lysine and hydroxylysine residues. LOX inhibition is the initiating molecular lesion
    of osteolathyrism and angiolathyrism.
  chemical_entities:
  - preferred_term: beta-aminopropionitrile
    term:
      id: CHEBI:27413
      label: beta-aminopropionitrile
  cell_types:
  - preferred_term: fibroblast
    term:
      id: CL:0000057
      label: fibroblast
  biological_processes:
  - preferred_term: peptidyl-lysine oxidation
    modifier: DECREASED
    term:
      id: GO:0018057
      label: peptidyl-lysine oxidation
  evidence:
  - reference: PMID:33462684
    reference_title: "Inhibition of lysyl oxidase stimulates TGF-β signaling and metalloproteinases-2 and -9 expression and contributes to the disruption of ascending aorta in rats: protection by propylthiouracil."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "LOX activity can be irreversibly inhibited by the administration of"
    explanation: "Establishes BAPN as an irreversible inhibitor of lysyl oxidase, the initiating lesion of connective-tissue lathyrism."
  - reference: PMID:25979340
    reference_title: "Lysyl Oxidase Activity Is Required for Ordered Collagen Fibrillogenesis by Tendon Cells."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "modify the side chain of lysyl residues in collagen and elastin"
    explanation: "Defines the lysyl oxidase reaction on collagen and elastin that BAPN blocks."
  downstream:
  - target: Collagen and Elastin Cross-link Failure
    description: Loss of LOX activity prevents covalent cross-linking of the extracellular matrix.
- name: Collagen and Elastin Cross-link Failure
  description: >-
    Without lysyl oxidase activity, collagen and elastin fail to form the non-reducible
    aldehyde-derived intermolecular cross-links required for tensile strength and proper
    fibril architecture. The extracellular matrix is mechanically weak and structurally
    abnormal, predisposing connective tissues throughout the body to failure.
  cell_types:
  - preferred_term: fibroblast
    term:
      id: CL:0000057
      label: fibroblast
  biological_processes:
  - preferred_term: collagen fibril organization
    modifier: ABNORMAL
    term:
      id: GO:0030199
      label: collagen fibril organization
  - preferred_term: extracellular matrix organization
    modifier: ABNORMAL
    term:
      id: GO:0030198
      label: extracellular matrix organization
  evidence:
  - reference: PMID:25979340
    reference_title: "Lysyl Oxidase Activity Is Required for Ordered Collagen Fibrillogenesis by Tendon Cells."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "the formation of aldimine-derived cross-links in collagen, and the constructs"
    explanation: "BAPN inhibition of LOX blocks collagen cross-link formation and yields mechanically weak, structurally abnormal matrix."
  downstream:
  - target: Skeletal Connective Tissue Weakening (Osteolathyrism)
    description: Weak collagen impairs bone matrix quality and skeletal integrity.
  - target: Aortic Wall Disruption with TGF-beta and MMP Upregulation (Angiolathyrism)
    description: Defective elastin/collagen cross-linking weakens the aortic wall.
- name: Skeletal Connective Tissue Weakening (Osteolathyrism)
  description: >-
    Defective collagen cross-linking degrades bone matrix quality and skeletal connective
    tissue, producing the skeletal deformities and periosteal/exostotic lesions of
    osteolathyrism. In a porcine BAPN model, osteolathyrism with skeletal changes arose as
    an unexpected systemic effect of lysyl oxidase inhibition.
  cell_types:
  - preferred_term: osteoblast
    term:
      id: CL:0000062
      label: osteoblast
  biological_processes:
  - preferred_term: extracellular matrix organization
    modifier: ABNORMAL
    term:
      id: GO:0030198
      label: extracellular matrix organization
  evidence:
  - reference: PMID:40545783
    reference_title: "CT Characteristics of Osteolathyrism in a Pig Model of β-Aminopropionitrile and Surgery-Induced Aortic Aneurysm."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "CT characteristics of osteolathyrism as an unexpected adverse event in both pigs"
    explanation: "BAPN administration in pigs produced osteolathyrism with skeletal changes detectable on CT."
- name: Aortic Wall Disruption with TGF-beta and MMP Upregulation (Angiolathyrism)
  conforms_to: "aortopathy_tgfbeta_dysregulation#TGF-beta Signaling Dysregulation"
  description: >-
    In angiolathyrism, defective elastin and collagen cross-linking weakens the aortic
    media. In rat models, lysyl oxidase inhibition by BAPN disrupts the ascending aortic
    wall and is accompanied by increased apoptosis, enhanced TGF-beta/SMAD2 signaling, and
    upregulation of matrix metalloproteinases MMP-2 and MMP-9 — a secondary remodeling
    cascade shared with heritable aortopathies — culminating in aneurysm, dissection, and
    rupture. This node conforms to the conserved aortopathy TGF-beta dysregulation hub,
    with BAPN-induced lysyl oxidase inhibition substituting for the heritable primary
    lesions (FBN1/TGFBR/SMAD3, etc.) as the upstream cause.
  cell_types:
  - preferred_term: vascular smooth muscle cell
    term:
      id: CL:0000359
      label: vascular associated smooth muscle cell
  biological_processes:
  - preferred_term: transforming growth factor beta receptor signaling pathway
    modifier: INCREASED
    term:
      id: GO:0007179
      label: transforming growth factor beta receptor signaling pathway
  - preferred_term: extracellular matrix disassembly
    modifier: INCREASED
    term:
      id: GO:0022617
      label: extracellular matrix disassembly
  evidence:
  - reference: PMID:33462684
    reference_title: "Inhibition of lysyl oxidase stimulates TGF-β signaling and metalloproteinases-2 and -9 expression and contributes to the disruption of ascending aorta in rats: protection by propylthiouracil."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "stimulated TGF-β signaling (increase of nuclear"
    explanation: "In rats, BAPN-induced LOX inhibition stimulates TGF-beta/SMAD2 signaling contributing to ascending aortic wall disruption."
  - reference: PMID:33462684
    reference_title: "Inhibition of lysyl oxidase stimulates TGF-β signaling and metalloproteinases-2 and -9 expression and contributes to the disruption of ascending aorta in rats: protection by propylthiouracil."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "up-regulated the expression of metalloproteinases-2 and"
    explanation: "MMP-2 and MMP-9 upregulation accompanies LOX inhibition and contributes to aortic wall destruction."
  - reference: PMID:20547706
    reference_title: "In search of a new therapeutic target for the treatment of genetically triggered thoracic aortic aneurysms and cardiovascular conditions: insights from human and animal lathyrism."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "particularly involving the vascular and skeletal systems, especially aortic"
    explanation: "Review of human and animal lathyrism documents vascular and skeletal connective-tissue disruption, especially aortic dissection/rupture."
phenotypes:
- name: Spastic paraplegia
  subtype: Neurolathyrism
  description: >-
    Bilateral spasticity and weakness of the lower limbs is the defining feature of
    neurolathyrism, reflecting upper motor neuron / corticospinal tract degeneration with
    sensory sparing.
  phenotype_term:
    preferred_term: Spastic paraplegia
    term:
      id: HP:0001258
      label: Spastic paraplegia
  evidence:
  - reference: PMID:37798732
    reference_title: "Prevalence of Neurolathyrism and its associated factors in Grass pea cultivation areas of Dawunt District, North-eastern Ethiopia; 2022: a community based multilevel analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Neurolathyrism is an upper motor neuron disorder characterized by"
    explanation: "Defines neurolathyrism by spastic paraparesis of upper-motor-neuron origin."
  - reference: PMID:36108319
    reference_title: "Neurolathyrism With Deep Vein Thrombosis and Bony Exostosis: Are They New Forms of Angiolathyrism and Osteolathyrism?"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "he had spastic paraparesis with brisk deep tendon reflexes and positive Babinski sign with sustained bilateral ankle clonus"
    explanation: "Clinical case documents spastic paraparesis with upper motor neuron signs."
- name: Lower limb spasticity
  subtype: Neurolathyrism
  description: Increased muscle tone in the legs producing stiffness and scissoring.
  phenotype_term:
    preferred_term: Lower limb spasticity
    term:
      id: HP:0002061
      label: Lower limb spasticity
  evidence:
  - reference: PMID:9577009
    reference_title: "Symptomatic treatment of neurolathyrism with tolperisone HCL (Mydocalm): a randomized double blind and placebo controlled drug trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "spastic muscle tone in the abductors, stiffness of Achilles and"
    explanation: "Randomized trial in neurolathyrism objectively measured spastic lower-limb muscle tone."
- name: Lower limb hyperreflexia
  subtype: Neurolathyrism
  description: Exaggerated deep tendon reflexes in the lower limbs, an upper motor neuron sign.
  phenotype_term:
    preferred_term: Lower limb hyperreflexia
    term:
      id: HP:0002395
      label: Lower limb hyperreflexia
  evidence:
  - reference: PMID:36108319
    reference_title: "Neurolathyrism With Deep Vein Thrombosis and Bony Exostosis: Are They New Forms of Angiolathyrism and Osteolathyrism?"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "he had spastic paraparesis with brisk deep tendon reflexes and positive Babinski sign with sustained bilateral ankle clonus"
    explanation: "Brisk deep tendon reflexes documented on examination, indicating lower-limb hyperreflexia."
- name: Babinski sign
  subtype: Neurolathyrism
  description: Extensor plantar response indicating corticospinal tract dysfunction.
  phenotype_term:
    preferred_term: Babinski sign
    term:
      id: HP:0003487
      label: Babinski sign
  evidence:
  - reference: PMID:36108319
    reference_title: "Neurolathyrism With Deep Vein Thrombosis and Bony Exostosis: Are They New Forms of Angiolathyrism and Osteolathyrism?"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "positive Babinski sign with sustained bilateral ankle clonus"
    explanation: "Positive Babinski sign documented on examination, a cardinal corticospinal sign."
- name: Clonus
  subtype: Neurolathyrism
  description: Sustained ankle clonus, an upper motor neuron sign elicited in neurolathyrism.
  phenotype_term:
    preferred_term: Clonus
    term:
      id: HP:0002169
      label: Clonus
  evidence:
  - reference: PMID:36108319
    reference_title: "Neurolathyrism With Deep Vein Thrombosis and Bony Exostosis: Are They New Forms of Angiolathyrism and Osteolathyrism?"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "sustained bilateral ankle clonus"
    explanation: "Sustained bilateral ankle clonus documented on examination."
  - reference: PMID:9577009
    reference_title: "Symptomatic treatment of neurolathyrism with tolperisone HCL (Mydocalm): a randomized double blind and placebo controlled drug trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "spastic muscle tone in the abductors, stiffness of Achilles and"
    explanation: "The same trial recorded spontaneous ankle clonus as an objective spasticity measure reduced by treatment."
- name: Spastic gait
  subtype: Neurolathyrism
  description: >-
    A stiff, scissoring gait; clinical severity in neurolathyrism is graded by walking
    ability from unaided through walking-stick stages to a bedridden state.
  phenotype_term:
    preferred_term: Spastic gait
    term:
      id: HP:0002064
      label: Spastic gait
  evidence:
  - reference: PMID:36108319
    reference_title: "Neurolathyrism With Deep Vein Thrombosis and Bony Exostosis: Are They New Forms of Angiolathyrism and Osteolathyrism?"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "a gradual decline in the power in the bilateral lower limbs, both in extension and flexion"
    explanation: "Progressive lower-limb motor decline leading to inability to walk, consistent with spastic gait."
- name: Lower limb muscle weakness
  subtype: Neurolathyrism
  description: Weakness of the leg muscles accompanying spasticity.
  phenotype_term:
    preferred_term: Lower limb muscle weakness
    term:
      id: HP:0007340
      label: Lower limb muscle weakness
  evidence:
  - reference: PMID:36108319
    reference_title: "Neurolathyrism With Deep Vein Thrombosis and Bony Exostosis: Are They New Forms of Angiolathyrism and Osteolathyrism?"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "a gradual decline in the power in the bilateral lower limbs, both in extension and flexion"
    explanation: "Documents progressive bilateral lower-limb weakness."
- category: Behavioral
  name: Depression
  subtype: Neurolathyrism
  description: >-
    Major depressive disorder is a frequent comorbidity among patients with established
    neurolathyrism, reflecting the burden of permanent disability, stigma, and social
    impact.
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Depression
    term:
      id: HP:0000716
      label: Depression
  evidence:
  - reference: PMID:38627754
    reference_title: "Prevalence of major depressive disorder and its associated factors among adult patients with neurolathyrism in Dawunt District, Ethiopia; 2022: community-based cross-sectional study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the prevalence of MDD was found to be 38.7%"
    explanation: "Community study found major depressive disorder in 38.7% of adult neurolathyrism patients."
- name: Aortic aneurysm
  subtype: Connective Tissue Lathyrism
  description: >-
    In angiolathyrism, defective elastin and collagen cross-linking weakens the aortic
    wall, predisposing to aneurysm. Documented primarily in animal models.
  phenotype_term:
    preferred_term: Aortic aneurysm
    term:
      id: HP:0004942
      label: Aortic aneurysm
  evidence:
  - reference: PMID:33462684
    reference_title: "Inhibition of lysyl oxidase stimulates TGF-β signaling and metalloproteinases-2 and -9 expression and contributes to the disruption of ascending aorta in rats: protection by propylthiouracil."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "BAPN administration caused disruption of the ascending aortic wall"
    explanation: "BAPN-induced lysyl oxidase inhibition disrupts the ascending aortic wall in rats."
- name: Aortic dissection
  subtype: Connective Tissue Lathyrism
  description: >-
    Aortic dissection and rupture from elastin/collagen cross-link failure, well
    documented in animal lathyrism.
  phenotype_term:
    preferred_term: Aortic dissection
    term:
      id: HP:0002647
      label: Aortic dissection
  evidence:
  - reference: PMID:20547706
    reference_title: "In search of a new therapeutic target for the treatment of genetically triggered thoracic aortic aneurysms and cardiovascular conditions: insights from human and animal lathyrism."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "particularly involving the vascular and skeletal systems, especially aortic"
    explanation: "Review documents aortic dissection/rupture as a hallmark of animal lathyrism."
- name: Skeletal dysplasia
  subtype: Connective Tissue Lathyrism
  description: >-
    Connective-tissue cross-link failure in osteolathyrism produces skeletal deformity and
    abnormal bone, shown in animal models.
  phenotype_term:
    preferred_term: Skeletal dysplasia
    term:
      id: HP:0002652
      label: Skeletal dysplasia
  evidence:
  - reference: PMID:40545783
    reference_title: "CT Characteristics of Osteolathyrism in a Pig Model of β-Aminopropionitrile and Surgery-Induced Aortic Aneurysm."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "CT characteristics of osteolathyrism as an unexpected adverse event in both pigs"
    explanation: "Porcine BAPN exposure produced osteolathyrism with skeletal changes on CT."
- name: Exostoses
  subtype: Connective Tissue Lathyrism
  description: >-
    Bony exostoses have been reported in association with osteolathyrism, including a
    single human neurolathyrism case with concurrent bony exostosis.
  phenotype_term:
    preferred_term: Exostoses
    term:
      id: HP:0100777
      label: Exostoses
  evidence:
  - reference: PMID:36108319
    reference_title: "Neurolathyrism With Deep Vein Thrombosis and Bony Exostosis: Are They New Forms of Angiolathyrism and Osteolathyrism?"
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "bony exostosis, which have never been reported in"
    explanation: "A single human case reports bony exostosis with neurolathyrism, proposed as a new osteolathyrism-like form; isolated finding."
environmental:
- name: Grass pea (Lathyrus sativus) overconsumption
  description: >-
    Sustained heavy dietary reliance on grass pea — typically over weeks to months during
    drought and famine when other crops fail — is the cause of neurolathyrism. Risk rises
    with feeding only grass pea, high grass-pea-to-cereal mixing ratios, and consumption of
    immature seeds. Grass pea is drought- and flood-tolerant and protein-rich, making it a
    famine survival food in parts of South Asia (India, Bangladesh, Nepal) and the Horn of
    Africa (Ethiopia). Male sex and older age are associated with higher risk.
  food_source:
    preferred_term: grass pea
    term:
      id: FOODON:00003735
      label: lathyrus pea
  evidence:
  - reference: PMID:37798732
    reference_title: "Prevalence of Neurolathyrism and its associated factors in Grass pea cultivation areas of Dawunt District, North-eastern Ethiopia; 2022: a community based multilevel analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "which is caused by the prolonged over-consumption of grass"
    explanation: "Community study attributes neurolathyrism to prolonged grass pea overconsumption."
  - reference: PMID:41965594
    reference_title: "Neurolathyrism in Delanta, Ethiopia: prevalence, associated factors, and social impact: a cross-sectional study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "male sex (AOR = 3.57; 95% CI = 1.79-7.10)"
    explanation: "Male sex is a significant risk factor for neurolathyrism."
treatments:
- name: Toxin Reduction by Food Processing
  description: >-
    Soaking, boiling and decanting, fermentation, or roasting grass pea substantially
    lowers beta-ODAP content and is a principal preventive measure where the crop remains a
    dietary staple.
  treatment_term:
    preferred_term: dietary intervention
    term:
      id: MAXO:0000088
      label: dietary intervention
  evidence:
  - reference: PMID:39329978
    reference_title: "The Potential of CRISPR/Cas9 to Circumvent the Risk Factor Neurotoxin β-N-oxalyl-L-α, β-diaminopropionic acid Limiting Wide Acceptance of the Underutilized Grass Pea (Lathyrus sativus L.)."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "traditional ways to reduce β-ODAP"
    explanation: "Review describes traditional food-processing methods that reduce beta-ODAP content."
- name: Dietary Diversification and Low-ODAP Cultivars
  description: >-
    Public-health prevention through dietary diversification, avoidance of exclusive grass
    pea reliance, and development of low-ODAP cultivars by classical breeding and, more
    recently, proposed gene-editing of the beta-ODAP biosynthetic pathway. Improving the
    low methionine/cysteine content of grass pea is a parallel nutritional goal.
  treatment_term:
    preferred_term: dietary intervention
    term:
      id: MAXO:0000088
      label: dietary intervention
    dietary_modifications:
    - action: RESTRICT
      food:
        preferred_term: grass pea
        term:
          id: FOODON:00003735
          label: lathyrus pea
      description: Reduce reliance on grass pea; substitute low-ODAP cultivars and other staples.
  evidence:
  - reference: PMID:39329978
    reference_title: "The Potential of CRISPR/Cas9 to Circumvent the Risk Factor Neurotoxin β-N-oxalyl-L-α, β-diaminopropionic acid Limiting Wide Acceptance of the Underutilized Grass Pea (Lathyrus sativus L.)."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "some varieties with low β-ODAP have been developed through classical breeding"
    explanation: "Low-beta-ODAP grass pea cultivars have been developed to reduce neurolathyrism risk."
- name: Antispasticity Pharmacotherapy
  description: >-
    Symptomatic treatment of spasticity. A randomized, double-blind, placebo-controlled
    trial showed the centrally acting muscle relaxant tolperisone improved spastic muscle
    tone, ankle clonus, and walking in neurolathyrism; other muscle relaxants such as
    baclofen are used clinically. The AMPA-receptor antagonist perampanel and gabapentin
    have been used for neuromuscular pain. Pharmacotherapy is symptomatic and does not
    reverse the underlying motor-neuron injury.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: tolperisone
      term:
        id: CHEBI:32244
        label: Tolperisone hydrochloride
  evidence:
  - reference: PMID:9577009
    reference_title: "Symptomatic treatment of neurolathyrism with tolperisone HCL (Mydocalm): a randomized double blind and placebo controlled drug trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "tolperisone is a well tolerated and efficacious"
    explanation: "Randomized controlled trial concluded tolperisone is efficacious for symptomatic treatment of neurolathyrism spasticity."
- name: Physical Therapy and Rehabilitation
  description: >-
    Physiotherapy, stretching, orthoses, and assistive devices to maintain mobility and
    reduce contractures in established neurolathyrism.
  treatment_term:
    preferred_term: physical therapy
    term:
      id: MAXO:0000011
      label: physical therapy
  evidence:
  - reference: PMID:36108319
    reference_title: "Neurolathyrism With Deep Vein Thrombosis and Bony Exostosis: Are They New Forms of Angiolathyrism and Osteolathyrism?"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "treatment largely remains supportive"
    explanation: "No specific cure exists; physiotherapy and supportive care are the mainstay of management."
- name: Supportive Care
  description: >-
    There is no disease-modifying therapy for established neurolathyrism; care is
    supportive, addressing disability, pain, and the high burden of psychosocial
    comorbidity (including major depressive disorder) through counselling and social
    support.
  treatment_term:
    preferred_term: supportive care
    term:
      id: MAXO:0000950
      label: supportive care
  evidence:
  - reference: PMID:38627754
    reference_title: "Prevalence of major depressive disorder and its associated factors among adult patients with neurolathyrism in Dawunt District, Ethiopia; 2022: community-based cross-sectional study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Neurolathyrism is a chronic illness characterized by lifelong incurable spastic"
    explanation: "Neurolathyrism is a lifelong, incurable disability requiring long-term supportive care."
diagnosis:
- name: Clinical diagnosis of neurolathyrism
  description: >-
    Neurolathyrism is a clinical diagnosis based on the syndrome of bilateral spastic
    paraparesis of upper-motor-neuron type (spasticity, hyperreflexia, Babinski sign,
    clonus) with characteristic sparing of sensation, together with a history of sustained
    grass pea (Lathyrus sativus) consumption. There is no confirmatory biomarker;
    electrophysiology and neuroimaging are typically normal and serve mainly to exclude
    mimics.
  diagnosis_term:
    preferred_term: physical examination
    term:
      id: MAXO:0000527
      label: physical examination
  markers: No confirmatory laboratory biomarker; diagnosis is clinical.
  results: >-
    Upper-motor-neuron signs in the lower limbs with sensory sparing and a positive dietary
    history; normal nerve conduction studies and neuroimaging.
  evidence:
  - reference: PMID:37798732
    reference_title: "Prevalence of Neurolathyrism and its associated factors in Grass pea cultivation areas of Dawunt District, North-eastern Ethiopia; 2022: a community based multilevel analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Neurolathyrism is an upper motor neuron disorder characterized by"
    explanation: "Defines the clinical syndrome (upper motor neuron disorder with spastic paraparesis) that anchors the diagnosis."
  - reference: PMID:36108319
    reference_title: "Neurolathyrism With Deep Vein Thrombosis and Bony Exostosis: Are They New Forms of Angiolathyrism and Osteolathyrism?"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "His electrophysiological studies and neuroimaging were otherwise normal"
    explanation: "Electrophysiology and neuroimaging are typically normal, supporting a clinical diagnosis after exclusion of mimics."
definitions:
- name: Clinical case definition of neurolathyrism
  definition_type: CASE_DEFINITION
  description: >-
    Neurolathyrism is defined as an upper motor neuron disorder presenting with spastic
    paraparesis of the lower limbs and sensory sparing, caused by prolonged over-consumption
    of grass pea (Lathyrus sativus) containing the neurotoxin beta-ODAP.
  scope: Disease-level clinical case definition for the neurolathyrism subtype.
  evidence:
  - reference: PMID:37798732
    reference_title: "Prevalence of Neurolathyrism and its associated factors in Grass pea cultivation areas of Dawunt District, North-eastern Ethiopia; 2022: a community based multilevel analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Neurolathyrism is an upper motor neuron disorder characterized by"
    explanation: "Community studies define neurolathyrism by upper-motor-neuron spastic paraparesis caused by grass pea over-consumption."
animal_models:
- species: Rattus norvegicus
  description: >-
    A neurolathyrism rat model produced by repeated peripheral L-beta-ODAP treatment of
    newborn rats under mild stress; affected rats develop hind-leg paraparesis (incidence
    ~25%) with motor-neuron depletion in lumbosacral spinal segments, recapitulating the
    human upper-motor-neuron syndrome.
  associated_phenotypes:
  - Hind-leg paraparesis
  - Lumbosacral motor neuron loss
  evidence:
  - reference: PMID:30930396
    reference_title: "[Research in Motor Neuron Diseases Caused by Natural Substances: Focus on Pathological Mechanisms of Neurolathyrism]."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "established a neurolathyrism rat model by repeated, peripheral"
    explanation: "Describes the newborn-rat L-beta-ODAP model of neurolathyrism."
  - reference: PMID:30930396
    reference_title: "[Research in Motor Neuron Diseases Caused by Natural Substances: Focus on Pathological Mechanisms of Neurolathyrism]."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "hind-leg paraparesis with an incidence rate of around 25%"
    explanation: "Affected rats develop hind-leg paraparesis at ~25% incidence, modeling the human motor deficit."
- species: Rattus norvegicus
  description: >-
    A BAPN angiolathyrism model in which lysyl oxidase inhibition disrupts the ascending
    aortic wall with increased apoptosis, enhanced TGF-beta/SMAD2 signaling, and MMP-2/-9
    upregulation, modeling the vascular form of lathyrism.
  associated_phenotypes:
  - Ascending aortic wall disruption
  - Aortic aneurysm
  evidence:
  - reference: PMID:33462684
    reference_title: "Inhibition of lysyl oxidase stimulates TGF-β signaling and metalloproteinases-2 and -9 expression and contributes to the disruption of ascending aorta in rats: protection by propylthiouracil."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "BAPN administration caused disruption of the ascending aortic wall"
    explanation: "BAPN-treated rats develop ascending aortic wall disruption, modeling angiolathyrism."
- species: Sus scrofa
  description: >-
    Pigs given oral BAPN to enhance surgically induced aortic aneurysm developed
    osteolathyrism with skeletal changes detectable on CT as an unexpected systemic effect
    of lysyl oxidase inhibition.
  associated_phenotypes:
  - Osteolathyrism with skeletal changes
  - Aortic aneurysm
  evidence:
  - reference: PMID:40545783
    reference_title: "CT Characteristics of Osteolathyrism in a Pig Model of β-Aminopropionitrile and Surgery-Induced Aortic Aneurysm."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "CT characteristics of osteolathyrism as an unexpected adverse event in both pigs"
    explanation: "Porcine BAPN exposure produced osteolathyrism with skeletal changes on CT."
- species: Gallus gallus
  description: >-
    A chick model used to profile proteome-wide brain changes after L-ODAP exposure,
    showing early induction of oxidative-stress and neurodegeneration-associated proteins.
  associated_phenotypes:
  - Brain oxidative-stress protein induction
  evidence:
  - reference: PMID:30057701
    reference_title: "Proteomic Changes in Chick Brain Proteome Post Treatment with Lathyrus Sativus Neurotoxin, β-N-Oxalyl-L-α,β-Diaminopropionic Acid (L-ODAP): A Better Insight to Transient Neurolathyrism."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "the proteome-wide alterations in chick brain"
    explanation: "Chick brain proteomics after L-ODAP reveals early oxidative-stress and neurodegeneration protein changes."
differential_diagnoses:
- name: Konzo (cassavism)
  description: >-
    Konzo is the closest mimic of neurolathyrism: an epidemic, abrupt-onset, symmetric
    upper-motor-neuron spastic paraparesis affecting young people during food shortages. It
    is caused by cyanide from insufficiently processed bitter cassava rather than by grass
    pea beta-ODAP.
  disease_term:
    preferred_term: konzo
    term:
      id: MONDO:0022666
      label: cassavism
  distinguishing_features:
  - Causative exposure is cyanogenic bitter cassava (Manihot esculenta), not grass pea.
  - Geographically clustered in sub-Saharan Africa (cassava-dependent regions).
  - Clinically near-identical upper-motor-neuron spastic paraparesis, so dietary history is the key discriminator.
  evidence:
  - reference: PMID:39608576
    reference_title: "New insight into the molecular etiopathogenesis of konzo: Cyanate could be a plausible neurotoxin contributing to konzo, contrary to thiocyanate."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "konzo, a tropical spastic paraparesis due to selective upper motor"
    explanation: "Konzo is an upper-motor-neuron spastic paraparesis from cassava-derived cyanide, mimicking neurolathyrism but with a distinct toxin."
  - reference: PMID:37620067
    reference_title: "Tropical spastic paraparesis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "excessive consumption of cyanide-containing bitter cassava"
    explanation: "Konzo arises from excessive consumption of cyanide-containing bitter cassava, distinguishing it from grass-pea neurolathyrism."
- name: Tropical spastic paraparesis (HTLV-1 myelopathy)
  description: >-
    HTLV-1-associated myelopathy / tropical spastic paraparesis produces a chronic spastic
    paraparesis that can resemble neurolathyrism but is caused by the retrovirus HTLV-1, is
    serologically diagnosable, and often involves sensory and bladder dysfunction.
  disease_term:
    preferred_term: tropical spastic paraparesis
    term:
      id: MONDO:0008039
      label: tropical spastic paraparesis
  distinguishing_features:
  - Infectious etiology (HTLV-1 retrovirus) confirmable by serology/PCR.
  - Frequently involves sensory and sphincter disturbance, whereas neurolathyrism characteristically spares sensation.
  - No history of grass pea consumption.
  evidence:
  - reference: PMID:37620067
    reference_title: "Tropical spastic paraparesis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "the retrovirus HTLV-1 is the causeof tropical spastic paraparesis/paraplegia or TSP"
    explanation: "TSP is caused by the retrovirus HTLV-1, distinguishing it from toxin-induced neurolathyrism (quote reproduces a spacing artifact in the source abstract)."

📚

References & Deep Research

Deep Research

1

Falcon ▸

1. Disease Information

Edison Scientific Literature 33 citations 2026-06-12T15:32:42.150004

1. Disease Information

1.1 Overview and current understanding

Lathyrism is an environmentally triggered, toxin-associated disorder caused by exposure to specific Lathyrus plant constituents leading to either (i) a neurodegenerative upper motor neuron syndrome (neurolathyrism) or (ii) connective-tissue pathology affecting bone and/or vasculature (osteo-/angiolathyrism). (bekelealemu2024thepotentialof pages 2-3, carlson2002caseiz16753 pages 3-4, merico2021inhibitionoflysyl pages 1-2)

Neurolathyrism is described as a neurodegenerative disease caused by “long-term overconsumption” of grass pea seeds containing the non-protein amino acid β-ODAP, producing an “irreversible spastic paraparesis of the legs while sparing sensory systems.” (bekelealemu2024thepotentialof pages 2-3)

A clinical case definition used in recent community work emphasized symmetrical spastic leg weakness with subacute/insidious onset, no sensory deficit, and history of grass pea consumption around onset. (yesuf2024prevalenceassociatedfactors pages 1-5)

1.2 Key identifiers and synonyms

Evidence in retrieved sources was insufficient to reliably populate ontology identifiers. The following identifiers were not found in the retrieved evidence and should be confirmed from OMIM/Orphanet/ICD/MeSH/MONDO directly before KB entry: - MONDO ID: not found in evidence (needs ontology lookup) - ICD-10/ICD-11 code(s): not found in evidence - MeSH descriptor(s): not found in evidence - Orphanet/OMIM identifiers: not found in evidence

Synonyms / alternative names (from local usage / literature in evidence): - “Neurolathyrism” (disease subtype) (bekelealemu2024thepotentialof pages 2-3, yesuf2024prevalenceassociatedfactors pages 1-5) - In Delanta, Ethiopia, the term “Yeguaya Beshita” is widely recognized as the local name for the condition (97.9% recognized the term). (yesuf2024prevalenceassociatedfactors pages 5-9)

1.3 Data provenance

The retrieved evidence includes aggregated population research (community cross-sectional surveys in Ethiopia) and experimental/mechanistic work (plant genomics/biochemistry and animal models). (yesuf2024prevalenceassociatedfactors pages 12-15, edwards2023genomicsandbiochemical pages 1-2, merico2021inhibitionoflysyl pages 1-2)

2. Etiology

2.1 Disease causal factors

Neurolathyrism (β-ODAP/β-L-ODAP; L. sativus)

Etiology is associated with ingestion of Lathyrus sativus containing a glutamate-analog neurotoxin; neurolathyrism is explicitly linked to the neurotoxin β-ODAP (β-L-ODAP). (yesuf2024prevalenceassociatedfactors pages 1-5, edwards2023genomicsandbiochemical pages 12-13)
β-ODAP exists as α and β isomers; the β-isomer is described as the toxic form accounting for ~99% of ODAP. (bekelealemu2024thepotentialof pages 2-3)

Osteolathyrism / Angiolathyrism (BAPN; L. odoratus; LOX inhibition)

BAPN is described as an irreversible inhibitor of lysyl oxidase (LOX), disrupting collagen and elastin cross-linking and causing osteolathyrism and vascular lesions including aneurysm/rupture in animal models. (carlson2002caseiz16753 pages 3-4, merico2021inhibitionoflysyl pages 1-2)

2.2 Risk factors

Environmental / dietary

Reliance on grass pea as a staple during adverse conditions: outbreaks are linked in review evidence to drought and reliance on grass pea as a major food source. (bekelealemu2024thepotentialof pages 2-3)
Nutritional status: sulfur amino acid deficiency is highlighted as increasing β-ODAP toxicity; supplementation with sulfur-containing amino acids is presented as risk-mitigating. (bekelealemu2024thepotentialof pages 2-3, bekelealemu2024thepotentialof pages 5-7)

Population-level and sociodemographic (recent Ethiopia data)

A 2022 community-based study in Delanta district, Ethiopia (n=470 analyzed) reported 56 cases (11.9% of participants) and estimated population prevalence 6.6%. (yesuf2024prevalenceassociatedfactors pages 1-5)

Multivariable associated factors included: - Male sex: AOR 3.569 (95% CI 1.794–7.098) (yesuf2024prevalenceassociatedfactors pages 12-15) - Older age (>46): AOR 2.690 (95% CI 1.064–9.341) (yesuf2024prevalenceassociatedfactors pages 12-15) - Inability to read: AOR 3.128 (95% CI 1.224–7.993) (yesuf2024prevalenceassociatedfactors pages 12-15) - Family size (reported as “less than 5” in one excerpt): AOR 2.332 (95% CI 1.159–4.692) (yesuf2024prevalenceassociatedfactors pages 12-15) - Farmland lease: AOR 2.734 (95% CI 1.23–6.06) (yesuf2024prevalenceassociatedfactors pages 12-15)

Note: Some odds ratio reporting appears inconsistently formatted across excerpts from the same preprint (e.g., “AOR=23%” with unusual CI formatting). Values above are taken from the excerpt that provided standard numeric AORs and CIs. (yesuf2024prevalenceassociatedfactors pages 12-15, yesuf2024prevalenceassociatedfactors pages 1-5)

2.3 Protective factors

Evidence in the retrieved dataset suggests: - Sulfur amino acid adequacy/supplementation (methionine, cysteine) may reduce β-ODAP neurotoxicity risk. (bekelealemu2024thepotentialof pages 2-3) - In neurolathyrism patients, regular exercise and formal counselling were associated with decreased odds of major depressive disorder (a comorbidity), suggesting plausible QoL-protective interventions in real-world care, though not primary prevention of neurolathyrism itself. (bimerew2024prevalenceofmajor pages 1-2)

2.4 Gene–environment interactions

No human genetic susceptibility loci/variants were identified in the retrieved evidence. However, genotype-by-environment (G×E) interactions are described in the context of grass pea toxin content, where classical breeding for low β-ODAP can be undermined by environmental effects increasing toxin levels. (bekelealemu2024thepotentialof pages 1-2)

3. Phenotypes

3.1 Core phenotypes by subtype

Neurolathyrism (human clinical)

Clinical features include: - Symmetrical spastic leg weakness, spastic gait, pyramidal signs (Babinski, clonus), progressive disability stages I–IV (walking stick dependence to bedridden with contractures). (yesuf2024prevalenceassociatedfactors pages 1-5) - “Irreversible spastic paraparesis” of legs with sensory sparing is emphasized in recent review evidence. (bekelealemu2024thepotentialof pages 2-3)

Suggested HPO terms (mapping; confirm exact best matches in HPO): - Spastic paraplegia: HP:0001258 - Spasticity: HP:0001257 - Abnormal gait: HP:0001288 - Hyperreflexia / Babinski sign: HP:0001347 / HP:0003487 (confirm) - Contractures (advanced): HP:0001371

Osteolathyrism (connective tissue/bone)

Bone deformity and periosteal proliferative exostoses at tendon insertion sites are described in BAPN intoxication; histology includes fibroblastic masses with cartilaginous and bone formation. (carlson2002caseiz16753 pages 3-4)

Suggested HPO terms: - Exostoses: HP:0100777 - Abnormal bone morphology: HP:0003330 - Muscle atrophy (secondary): HP:0003202

Angiolathyrism (vascular)

Aortic/arterial aneurysm and rupture/dissection is described with LOX inhibition by BAPN in animal models and mechanistic vascular wall disruption. (merico2021inhibitionoflysyl pages 1-2, carlson2002caseiz16753 pages 1-3)

Suggested HPO terms: - Aortic aneurysm: HP:0004942 - Aortic dissection: HP:0002647

3.2 Onset, severity, progression

Neurolathyrism can present with subacute/insidious onset and progresses across clinically staged disability levels (I–IV). (yesuf2024prevalenceassociatedfactors pages 1-5)
In a neurolathyrism patient sample (Dawunt district), reported onset age range was 4–37 years (mean 17.32 ± 7.91) with disease duration 4–40 years (mean 17.95 ± 8.28), consistent with long-term disability. (bimerew2024prevalenceofmajor pages 2-4)

3.3 Quality-of-life and psychosocial impact (recent data)

In Delanta, Ethiopia, substantial social impact was reported: 73% discontinued school and 21.4% were divorced after the disease. (yesuf2026neurolathyrismindelanta pages 1-2)
Among adult neurolathyrism patients in Dawunt district, Ethiopia, major depressive disorder prevalence was 38.7%. (bimerew2024prevalenceofmajor pages 1-2)

4. Genetic/Molecular Information

4.1 Human causal genes and pathogenic variants

Lathyrism is primarily an environmental/toxin-mediated condition in the retrieved sources; no causal human genes or variants were identified in the evidence provided. (bekelealemu2024thepotentialof pages 2-3, yesuf2024prevalenceassociatedfactors pages 1-5)

4.2 Plant/crop molecular genetics relevant to risk mitigation (2023–2024 priority)

A major 2023 advance was a long-read genome assembly for L. sativus and biochemical elucidation of the β-L-ODAP biosynthetic pathway. - Edwards et al. (Nature Communications, Feb 2023) report an annotated ~6.5 Gbp L. sativus genome and identify a final-step metabolon involving LsAAE3 (acyl-activating enzyme 3) and LsBOS (a BAHD acyltransferase), “CoA-activated to produce β-L-ODAP.” (edwards2023genomicsandbiochemical pages 1-2) - Pathway-related loci include CAS (β-cyanoalanine synthase) and CS (cysteine synthase) genes, with multiple CS-like copies annotated. (edwards2023genomicsandbiochemical pages 2-4)

A 2024 review proposes gene-editing strategies: - Bekele-Alemu et al. (Current Issues in Molecular Biology, Sep 2024) identify key enzymes β-ODAP synthase (BOS) and β-cyanoalanine synthase (CAS) and propose CRISPR/Cas9 strategies: BOS knockout, CAS knockout, BOS+CAS knockout, or targeted substitutions to reduce toxin while monitoring precursor accumulation. (bekelealemu2024thepotentialof pages 11-13)

Suggested ontology mappings (plant/crop context; for KB cross-references): - Chemical entity: β-ODAP / β-L-ODAP (CHEBI ID not in evidence; needs CHEBI lookup)

5. Environmental Information

5.1 Environmental factors

Food-system stressors: community data emphasize grass pea’s centrality as a primary food and note that “banning grass pea is not feasible” locally due to weather variability leading to overconsumption risk. (yesuf2024prevalenceassociatedfactors pages 5-9)

5.2 Lifestyle factors

No smoking/alcohol or other lifestyle exposures were identified as causal in the retrieved evidence. Exercise appears in the context of mental-health comorbidity reduction rather than primary disease prevention. (bimerew2024prevalenceofmajor pages 1-2)

5.3 Infectious agents

Not applicable based on retrieved evidence.

6. Mechanism / Pathophysiology

6.1 Neurolathyrism causal chain (β-ODAP)

Trigger: prolonged exposure to β-ODAP/β-L-ODAP from grass pea diets (often under drought/food insecurity). (bekelealemu2024thepotentialof pages 2-3)

Molecular/cellular: β-ODAP is described as an excitatory amino acid agonist at AMPA receptors, associated with intracellular Ca2+ overload, mitochondrial respiration disturbance, reduced amino acid transport, and increased oxidative stress, leading to excitotoxic motor neuron degeneration and paralysis. (bekelealemu2024thepotentialof pages 5-7)

Tissue/system: degeneration of corticospinal/pyramidal tract neurons in spinal cord/leg cortex producing spastic paraparesis. (bekelealemu2024thepotentialof pages 2-3)

Suggested GO biological processes (confirm in GO): - Excitotoxicity / glutamate receptor signaling pathway - Neuron death: GO:0070997 (neuron death) (confirm) - Oxidative stress response: GO:0006979

Suggested CL cell types (confirm in Cell Ontology): - Motor neuron: CL:0000100

6.2 Osteo-/angiolathyrism causal chain (BAPN → LOX inhibition)

Trigger: BAPN exposure (classically linked to L. odoratus ingestion; also used experimentally). (carlson2002caseiz16753 pages 3-4, merico2021inhibitionoflysyl pages 1-2)

Molecular: BAPN irreversibly inhibits LOX, disrupting oxidative deamination of lysine/hydroxylysine residues in collagen/elastin and preventing normal intermolecular covalent cross-links required for tensile strength and ECM maturation. (carlson2002caseiz16753 pages 3-4, merico2021inhibitionoflysyl pages 1-2)

Downstream vascular remodeling: In a rat model, LOX inhibition is associated with increased apoptosis, stimulated TGF-β signaling (p-SMAD2), and increased MMP-2/MMP-9 expression contributing to ascending aorta disruption. (merico2021inhibitionoflysyl pages 1-2)

Tissue/system manifestations: - Bone: periosteal exostoses and fibro-osseous lesions; impaired bone quality and remodeling. (carlson2002caseiz16753 pages 3-4, suliman2023theeffectsof pages 1-2) - Vasculature: aortic/arterial aneurysm and fatal rupture in models. (merico2021inhibitionoflysyl pages 1-2, carlson2002caseiz16753 pages 1-3)

Suggested GO terms: - Collagen fibril organization: GO:0030199 - Elastic fiber assembly: GO:0048251 (confirm) - Extracellular matrix organization: GO:0030198 - TGF-β receptor signaling pathway: GO:0007179 - Matrix metalloproteinase activation / extracellular matrix disassembly: GO:0022617

Suggested CL cell types: - Vascular smooth muscle cell: CL:0000192 - Fibroblast: CL:0000057 - Osteoblast: CL:0000062 - Osteocyte: CL:0000136

7. Anatomical Structures Affected

7.1 Organ/system level

Neurolathyrism: central motor pathways (corticospinal/pyramidal tract) with predominant lower-limb functional deficit. (bekelealemu2024thepotentialof pages 2-3, yesuf2024prevalenceassociatedfactors pages 1-5)
Angiolathyrism: ascending aorta / major arteries (aneurysm/dissection/rupture). (merico2021inhibitionoflysyl pages 1-2, carlson2002caseiz16753 pages 1-3)
Osteolathyrism: bone at tendon insertion sites; impaired bone matrix/collagen quality. (carlson2002caseiz16753 pages 3-4, suliman2023theeffectsof pages 1-2)

7.2 Suggested UBERON terms (confirm exact IDs)

Spinal cord (UBERON:0002240)
Cerebral cortex / motor cortex (UBERON:0000956)
Ascending aorta (UBERON:0001496)
Femur (UBERON:0000981)

8. Temporal Development

Neurolathyrism is described as lifelong/incurable spastic paralysis in the Ethiopian patient study context. (bimerew2024prevalenceofmajor pages 1-2)
Community staging (I–IV) reflects progressive functional impairment from spastic gait to being bedridden with contractures. (yesuf2024prevalenceassociatedfactors pages 1-5)

9. Inheritance and Population

9.1 Inheritance

Not applicable: evidence supports an environmental/toxin-driven etiology; no Mendelian inheritance described. (bekelealemu2024thepotentialof pages 2-3)

9.2 Epidemiology (recent statistics)

Delanta district, Ethiopia (survey Nov–Dec 2022; posted May 2024): - n=470 analyzed; 56 cases (11.9% of participants) and “population-level prevalence … 6.6%.” (yesuf2024prevalenceassociatedfactors pages 1-5)

Dawunt district, Ethiopia (community study referenced in BMC Psychiatry Apr 2024): - Point prevalence reported as 2.4% (95% CI 2.0–3.0). (bimerew2024prevalenceofmajor pages 2-4)

10. Diagnostics

10.1 Clinical criteria (from recent community study definition)

Neurolathyrism diagnosis in community work relied on a clinical syndrome of spastic paraparesis with sensory sparing and dietary exposure history (grass pea consumption). (yesuf2024prevalenceassociatedfactors pages 1-5)

10.2 Differential diagnosis

No detailed differential diagnosis workup was found in the retrieved evidence; common differentials in clinical neurology (e.g., hereditary spastic paraplegia, myelopathy, MS, B12 deficiency) should be validated from clinical references not retrieved here.

10.3 Biomarkers / laboratory tests

No validated human diagnostic biomarker assays were identified in the retrieved evidence.

11. Outcome / Prognosis

Neurolathyrism is described as irreversible with “lifelong incurable spastic paralysis of lower extremities” in the Ethiopian patient study context. (bimerew2024prevalenceofmajor pages 1-2)
Major morbidity includes mobility impairment: in Delanta, 100% of cases had walking difficulty and 96.4% relied on a walking stick. (yesuf2024prevalenceassociatedfactors pages 9-12)

12. Treatment

12.1 Pharmacotherapy

No disease-modifying pharmacotherapy for established neurolathyrism was identified in the retrieved evidence.

12.2 Supportive and rehabilitative care

Evidence supports supportive interventions addressing disability and mental health: - Formal counselling and regular exercise were associated with decreased odds of major depressive disorder among neurolathyrism patients. (bimerew2024prevalenceofmajor pages 1-2)

Suggested MAXO terms (confirm IDs in MAXO): - Physical therapy / exercise therapy - Psychological counselling - Assistive device use (walking aids)

13. Prevention

13.1 Primary prevention (risk reduction)

The retrieved evidence supports prevention as primarily food-system and agricultural/toxin-exposure mitigation, including: - Reducing β-ODAP in grass pea via plant breeding/genomics and potentially CRISPR-based targeting of BOS/CAS pathway genes. (bekelealemu2024thepotentialof pages 11-13, edwards2023genomicsandbiochemical pages 1-2) - Nutritional strategies (improving sulfur amino acid adequacy) to reduce β-ODAP neurotoxicity risk. (bekelealemu2024thepotentialof pages 2-3)

13.2 Real-world implementations and applications

Genomics-enabled crop improvement: availability of a high-quality L. sativus genome and identified biosynthetic genes provides a concrete implementation pathway for developing low-toxin cultivars for food security contexts. (edwards2023genomicsandbiochemical pages 1-2, edwards2023genomicsandbiochemical pages 2-4)
Public health: the Delanta study explicitly calls for inclusion of lathyrism in national disease reporting and targeted prevention policies, reflecting real-world surveillance implications. (yesuf2024prevalenceassociatedfactors pages 1-5)

14. Other Species / Natural Disease

Animal susceptibility is supported in lathyrism literature cited by aortic rupture in turkeys fed L. odoratus and BAPN-induced aneurysm/rupture models. (sherif2010insearchof pages 3-4, carlson2002caseiz16753 pages 1-3)

NCBI Taxon identifiers and OMIA links were not retrievable from the current evidence set.

15. Model Organisms

15.1 Induced models

BAPN (LOX inhibition) models in rats reproduce key features of angiolathyrism (ascending aortic disruption, MMP/TGF-β activation) and osteolathyrism (defective collagen cross-linking/bone pathology). (merico2021inhibitionoflysyl pages 1-2, suliman2023theeffectsof pages 1-2)

15.2 Model limitations

The retrieved evidence does not provide direct head-to-head validation against human lathyrism phenotypes for all endpoints; caution is warranted when translating vascular/bone findings to human disease.

Recent developments (2023–2024) highlighted

Pathway resolution and genome resource: 2023 Nature Communications work produced a chromosome-scale genome assembly and identified LsAAE3–LsBOS metabolon controlling final β-L-ODAP production. (edwards2023genomicsandbiochemical pages 1-2)
Genome-editing proposals: 2024 review proposed CRISPR/Cas9 targeting BOS and CAS (including multi-target strategies and amino-acid substitutions) to reduce β-ODAP. (bekelealemu2024thepotentialof pages 11-13)
New epidemiologic measurements and social impact quantification: 2024 Ethiopia community work provided updated prevalence estimates and quantified social consequences (school discontinuation, divorce) and mobility impairment rates. (yesuf2024prevalenceassociatedfactors pages 9-12, yesuf2026neurolathyrismindelanta pages 1-2)

Evidence-based statistics (from recent studies)

Delanta (Ethiopia) neurolathyrism prevalence: 56/470 (11.9% of participants) and estimated population prevalence 6.6%. (yesuf2024prevalenceassociatedfactors pages 1-5)
Dawunt (Ethiopia) point prevalence: 2.4% (95% CI 2.0–3.0). (bimerew2024prevalenceofmajor pages 2-4)
Neurolathyrism patient comorbidity: major depressive disorder prevalence 38.7% among adult neurolathyrism patients (PHQ-9 ≥10). (bimerew2024prevalenceofmajor pages 1-2)

Direct quotes from abstracts (available in retrieved evidence)

Bimerew et al. (BMC Psychiatry, Apr 2024) describes neurolathyrism as: “a chronic illness characterized by lifelong incurable spastic paralysis of lower extremities; causing permanent disability.” (bimerew2024prevalenceofmajor pages 1-2)
The same abstract reports: “the prevalence of MDD was found to be 38.7%.” (bimerew2024prevalenceofmajor pages 1-2)

Key references with URLs and dates (prioritizing 2023–2024)

Edwards A. et al. Nature Communications (Feb 2023). “Genomics and biochemical analyses reveal a metabolon key to β-L-ODAP biosynthesis in Lathyrus sativus.” https://doi.org/10.1038/s41467-023-36503-2 (edwards2023genomicsandbiochemical pages 1-2)
Bekele-Alemu A. et al. Current Issues in Molecular Biology (Sep 2024). “The Potential of CRISPR/Cas9 to Circumvent the Risk Factor Neurotoxin β-N-oxalyl-L-α, β-diaminopropionic acid…” https://doi.org/10.3390/cimb46090626 (bekelealemu2024thepotentialof pages 11-13)
Yesuf A.E. et al. Preprint (May 2024). “Prevalence, Associated Factors, and Social Status of Patients with Neurolathyrisim in Delanta…” https://doi.org/10.21203/rs.3.rs-4332232/v1 (yesuf2024prevalenceassociatedfactors pages 1-5)
Bimerew M. et al. BMC Psychiatry (Apr 2024). “Prevalence of major depressive disorder… among adult patients with neurolathyrism…” https://doi.org/10.1186/s12888-024-05755-7 (bimerew2024prevalenceofmajor pages 1-2)

Major gaps in the retrieved evidence (needs follow-up retrieval for KB completeness)

Standard disease identifiers (MONDO/MeSH/ICD/Orphanet/OMIM) were not available in the retrieved text evidence.
No primary human neuropathology/neuroimaging studies, nor prospective incidence estimates, were retrieved.
No human genetic susceptibility data were retrieved.
No formal diagnostic criteria guidelines or treatment guidelines were retrieved.

These gaps should be filled by targeted ontology lookup (MONDO/MeSH/ICD), and PubMed retrieval of clinical neurology reviews and historical/modern neuropathology studies.

References

(bekelealemu2024thepotentialof pages 2-3): Abreham Bekele-Alemu, Deribew Girma-Tola, and Ayalew Ligaba-Osena. The potential of crispr/cas9 to circumvent the risk factor neurotoxin β-n-oxalyl-l-α, β-diaminopropionic acid limiting wide acceptance of the underutilized grass pea (lathyrus sativus l.). Current Issues in Molecular Biology, 46:10570-10589, Sep 2024. URL: https://doi.org/10.3390/cimb46090626, doi:10.3390/cimb46090626. This article has 6 citations.
(yesuf2024prevalenceassociatedfactors pages 1-5): Andualem Endrias Yesuf, Eden Efrem Mersiehazen, Bemnet Yazew Abegaz, Samson Zegeye Endale, Beyadiglign Wondimu Gebresilssie, and Biniyam Jemaneh Batu. Prevalence, associated factors, and social status of patients with neurolathyrisim in delanta, amhara region, ethiopia: a community-based cross- sectional study. Unknown journal, May 2024. URL: https://doi.org/10.21203/rs.3.rs-4332232/v1, doi:10.21203/rs.3.rs-4332232/v1.
(carlson2002caseiz16753 pages 3-4): CS Carlson. Case i: z16753 (afip 3138054). Unknown journal, 2002.
(merico2021inhibitionoflysyl pages 1-2): Valeria Merico, Jacopo Francesco Imberti, Mario Zanoni, Giuseppe Boriani, Silvia Garagna, and Roberto Imberti. Inhibition of lysyl oxidase stimulates tgf-β signaling and metalloproteinases-2 and -9 expression and contributes to the disruption of ascending aorta in rats: protection by propylthiouracil. Heart and Vessels, 36:738-747, Jan 2021. URL: https://doi.org/10.1007/s00380-020-01750-6, doi:10.1007/s00380-020-01750-6. This article has 7 citations and is from a peer-reviewed journal.
(bekelealemu2024thepotentialof pages 5-7): Abreham Bekele-Alemu, Deribew Girma-Tola, and Ayalew Ligaba-Osena. The potential of crispr/cas9 to circumvent the risk factor neurotoxin β-n-oxalyl-l-α, β-diaminopropionic acid limiting wide acceptance of the underutilized grass pea (lathyrus sativus l.). Current Issues in Molecular Biology, 46:10570-10589, Sep 2024. URL: https://doi.org/10.3390/cimb46090626, doi:10.3390/cimb46090626. This article has 6 citations.
(edwards2023genomicsandbiochemical pages 12-13): Anne Edwards, Isaac Njaci, Abhimanyu Sarkar, Zhouqian Jiang, Gemy George Kaithakottil, Christopher Moore, Jitender Cheema, Clare E. M. Stevenson, Martin Rejzek, Petr Novák, Marielle Vigouroux, Martin Vickers, Roland H. M. Wouters, Pirita Paajanen, Burkhard Steuernagel, Jonathan D. Moore, Janet Higgins, David Swarbreck, Stefan Martens, Colin Y. Kim, Jing-Ke Weng, Sagadevan Mundree, Benjamin Kilian, Shiv Kumar, Matt Loose, Levi Yant, Jiří Macas, Trevor L. Wang, Cathie Martin, and Peter M. F. Emmrich. Genomics and biochemical analyses reveal a metabolon key to β-l-odap biosynthesis in lathyrus sativus. Nature Communications, Feb 2023. URL: https://doi.org/10.1038/s41467-023-36503-2, doi:10.1038/s41467-023-36503-2. This article has 43 citations and is from a highest quality peer-reviewed journal.
(edwards2023genomicsandbiochemical pages 1-2): Anne Edwards, Isaac Njaci, Abhimanyu Sarkar, Zhouqian Jiang, Gemy George Kaithakottil, Christopher Moore, Jitender Cheema, Clare E. M. Stevenson, Martin Rejzek, Petr Novák, Marielle Vigouroux, Martin Vickers, Roland H. M. Wouters, Pirita Paajanen, Burkhard Steuernagel, Jonathan D. Moore, Janet Higgins, David Swarbreck, Stefan Martens, Colin Y. Kim, Jing-Ke Weng, Sagadevan Mundree, Benjamin Kilian, Shiv Kumar, Matt Loose, Levi Yant, Jiří Macas, Trevor L. Wang, Cathie Martin, and Peter M. F. Emmrich. Genomics and biochemical analyses reveal a metabolon key to β-l-odap biosynthesis in lathyrus sativus. Nature Communications, Feb 2023. URL: https://doi.org/10.1038/s41467-023-36503-2, doi:10.1038/s41467-023-36503-2. This article has 43 citations and is from a highest quality peer-reviewed journal.
(suliman2023theeffectsof pages 1-2): Mubarak Suliman, Masako Nagasawa, Farah A. Al-Omari, and Katsumi Uoshima. The effects of collagen cross-link deficiency on osseointegration process of pure titanium implants. Journal of prosthodontic research, 68:449-455, Oct 2023. URL: https://doi.org/10.2186/jpr.jpr_d_22_00249, doi:10.2186/jpr.jpr_d_22_00249. This article has 2 citations and is from a domain leading peer-reviewed journal.
(carlson2002caseiz16753 pages 1-3): CS Carlson. Case i: z16753 (afip 3138054). Unknown journal, 2002.
(yesuf2024prevalenceassociatedfactors pages 5-9): Andualem Endrias Yesuf, Eden Efrem Mersiehazen, Bemnet Yazew Abegaz, Samson Zegeye Endale, Beyadiglign Wondimu Gebresilssie, and Biniyam Jemaneh Batu. Prevalence, associated factors, and social status of patients with neurolathyrisim in delanta, amhara region, ethiopia: a community-based cross- sectional study. Unknown journal, May 2024. URL: https://doi.org/10.21203/rs.3.rs-4332232/v1, doi:10.21203/rs.3.rs-4332232/v1.
(yesuf2024prevalenceassociatedfactors pages 12-15): Andualem Endrias Yesuf, Eden Efrem Mersiehazen, Bemnet Yazew Abegaz, Samson Zegeye Endale, Beyadiglign Wondimu Gebresilssie, and Biniyam Jemaneh Batu. Prevalence, associated factors, and social status of patients with neurolathyrisim in delanta, amhara region, ethiopia: a community-based cross- sectional study. Unknown journal, May 2024. URL: https://doi.org/10.21203/rs.3.rs-4332232/v1, doi:10.21203/rs.3.rs-4332232/v1.
(bimerew2024prevalenceofmajor pages 1-2): Melaku Bimerew, Teshome Gebremeskel, Biruk Beletew, Wondye Ayaliew, Mulugeta Wodaje, and Manay Ayalneh. Prevalence of major depressive disorder and its associated factors among adult patients with neurolathyrism in dawunt district, ethiopia; 2022: community-based cross-sectional study. BMC Psychiatry, Apr 2024. URL: https://doi.org/10.1186/s12888-024-05755-7, doi:10.1186/s12888-024-05755-7. This article has 10 citations and is from a domain leading peer-reviewed journal.
(bekelealemu2024thepotentialof pages 1-2): Abreham Bekele-Alemu, Deribew Girma-Tola, and Ayalew Ligaba-Osena. The potential of crispr/cas9 to circumvent the risk factor neurotoxin β-n-oxalyl-l-α, β-diaminopropionic acid limiting wide acceptance of the underutilized grass pea (lathyrus sativus l.). Current Issues in Molecular Biology, 46:10570-10589, Sep 2024. URL: https://doi.org/10.3390/cimb46090626, doi:10.3390/cimb46090626. This article has 6 citations.
(bimerew2024prevalenceofmajor pages 2-4): Melaku Bimerew, Teshome Gebremeskel, Biruk Beletew, Wondye Ayaliew, Mulugeta Wodaje, and Manay Ayalneh. Prevalence of major depressive disorder and its associated factors among adult patients with neurolathyrism in dawunt district, ethiopia; 2022: community-based cross-sectional study. BMC Psychiatry, Apr 2024. URL: https://doi.org/10.1186/s12888-024-05755-7, doi:10.1186/s12888-024-05755-7. This article has 10 citations and is from a domain leading peer-reviewed journal.
(yesuf2026neurolathyrismindelanta pages 1-2): Andualem Endrias Yesuf, Eden Efrem Mersiehazen, Bemnet Yazew Abegaz, Samson Zegeye Endale, Beyadiglign Wondimu Gebresilssie, and Biniyam Jemaneh Batu. Neurolathyrism in delanta, ethiopia: prevalence, associated factors, and social impact: a cross-sectional study. BMC Neurology, Apr 2026. URL: https://doi.org/10.1186/s12883-026-04871-z, doi:10.1186/s12883-026-04871-z. This article has 0 citations and is from a peer-reviewed journal.
(edwards2023genomicsandbiochemical pages 2-4): Anne Edwards, Isaac Njaci, Abhimanyu Sarkar, Zhouqian Jiang, Gemy George Kaithakottil, Christopher Moore, Jitender Cheema, Clare E. M. Stevenson, Martin Rejzek, Petr Novák, Marielle Vigouroux, Martin Vickers, Roland H. M. Wouters, Pirita Paajanen, Burkhard Steuernagel, Jonathan D. Moore, Janet Higgins, David Swarbreck, Stefan Martens, Colin Y. Kim, Jing-Ke Weng, Sagadevan Mundree, Benjamin Kilian, Shiv Kumar, Matt Loose, Levi Yant, Jiří Macas, Trevor L. Wang, Cathie Martin, and Peter M. F. Emmrich. Genomics and biochemical analyses reveal a metabolon key to β-l-odap biosynthesis in lathyrus sativus. Nature Communications, Feb 2023. URL: https://doi.org/10.1038/s41467-023-36503-2, doi:10.1038/s41467-023-36503-2. This article has 43 citations and is from a highest quality peer-reviewed journal.
(bekelealemu2024thepotentialof pages 11-13): Abreham Bekele-Alemu, Deribew Girma-Tola, and Ayalew Ligaba-Osena. The potential of crispr/cas9 to circumvent the risk factor neurotoxin β-n-oxalyl-l-α, β-diaminopropionic acid limiting wide acceptance of the underutilized grass pea (lathyrus sativus l.). Current Issues in Molecular Biology, 46:10570-10589, Sep 2024. URL: https://doi.org/10.3390/cimb46090626, doi:10.3390/cimb46090626. This article has 6 citations.
(yesuf2024prevalenceassociatedfactors pages 9-12): Andualem Endrias Yesuf, Eden Efrem Mersiehazen, Bemnet Yazew Abegaz, Samson Zegeye Endale, Beyadiglign Wondimu Gebresilssie, and Biniyam Jemaneh Batu. Prevalence, associated factors, and social status of patients with neurolathyrisim in delanta, amhara region, ethiopia: a community-based cross- sectional study. Unknown journal, May 2024. URL: https://doi.org/10.21203/rs.3.rs-4332232/v1, doi:10.21203/rs.3.rs-4332232/v1.
(sherif2010insearchof pages 3-4): H. M. F. Sherif. In search of a new therapeutic target for the treatment of genetically triggered thoracic aortic aneurysms and cardiovascular conditions: insights from human and animal lathyrism. Interactive CardioVascular and Thoracic Surgery, 11:271-276, Jun 2010. URL: https://doi.org/10.1510/icvts.2010.239681, doi:10.1510/icvts.2010.239681. This article has 29 citations.

Artifacts

Edison artifact artifact-00

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OpenScientist Report

Mappings

Definitions

Subtypes

Pathophysiology

Pathograph

Phenotypes

Medical Actions

Environmental Factors

Differential Diagnoses

Source YAML

References & Deep Research

Deep Research

1. Disease Information

1.1 Overview and current understanding

1.2 Key identifiers and synonyms

1.3 Data provenance

2. Etiology

2.1 Disease causal factors

Neurolathyrism (β-ODAP/β-L-ODAP; L. sativus)

Osteolathyrism / Angiolathyrism (BAPN; L. odoratus; LOX inhibition)

2.2 Risk factors

Environmental / dietary

Population-level and sociodemographic (recent Ethiopia data)

2.3 Protective factors

2.4 Gene–environment interactions

3. Phenotypes

3.1 Core phenotypes by subtype

Neurolathyrism (human clinical)

Osteolathyrism (connective tissue/bone)

Angiolathyrism (vascular)

3.2 Onset, severity, progression

3.3 Quality-of-life and psychosocial impact (recent data)

4. Genetic/Molecular Information

4.1 Human causal genes and pathogenic variants

4.2 Plant/crop molecular genetics relevant to risk mitigation (2023–2024 priority)

5. Environmental Information

5.1 Environmental factors

5.2 Lifestyle factors

5.3 Infectious agents

6. Mechanism / Pathophysiology

6.1 Neurolathyrism causal chain (β-ODAP)

6.2 Osteo-/angiolathyrism causal chain (BAPN → LOX inhibition)

7. Anatomical Structures Affected

7.1 Organ/system level

7.2 Suggested UBERON terms (confirm exact IDs)

8. Temporal Development

9. Inheritance and Population

9.1 Inheritance

9.2 Epidemiology (recent statistics)

10. Diagnostics

10.1 Clinical criteria (from recent community study definition)

10.2 Differential diagnosis

10.3 Biomarkers / laboratory tests

11. Outcome / Prognosis

12. Treatment

12.1 Pharmacotherapy

12.2 Supportive and rehabilitative care

13. Prevention

13.1 Primary prevention (risk reduction)

13.2 Real-world implementations and applications

14. Other Species / Natural Disease

15. Model Organisms

15.1 Induced models

15.2 Model limitations

Recent developments (2023–2024) highlighted

Evidence-based statistics (from recent studies)

Direct quotes from abstracts (available in retrieved evidence)

Key references with URLs and dates (prioritizing 2023–2024)

Major gaps in the retrieved evidence (needs follow-up retrieval for KB completeness)

Artifacts