Konzo

Environmental MONDO:0022666 Pathograph 4 Show in embeddings browser Motor Neuron Disease Foodborne Disease

Konzo (cassavism) is an acute-onset, symmetric, permanent and irreversible upper motor neuron disease producing spastic paraparesis of the legs, epidemic and endemic in cassava-dependent regions of sub-Saharan Africa. It is caused by sustained monotonous consumption of insufficiently processed bitter cassava (Manihot esculenta) containing the cyanogenic glucoside linamarin, combined with a protein-poor diet low in sulfur-containing amino acids; the resulting chronic high dietary cyanide exposure cannot be adequately detoxified, leading to selective injury of upper motor neurons and the corticospinal (pyramidal) tracts with characteristic sparing of sensory and genitourinary function. Outbreaks cluster during droughts and food shortages and disproportionately affect children and women of childbearing age. Konzo is clinically near-identical to grass-pea neurolathyrism (a distinct toxic spastic paraparesis) and is distinguished from tropical ataxic neuropathy and HTLV-1-associated tropical spastic paraparesis. There is no cure; management is supportive and rehabilitative, and prevention relies on cassava detoxification (the wetting method) and dietary diversification.

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1
Mappings
1
Definitions
4
Pathophys.
5
Phenotypes
4
Pathograph
4
Medical Actions
3
Differentials
🔗

Mappings

MONDO
MONDO:0022666 cassavism
skos:exactMatch MONDO
Primary MONDO disease identifier for this konzo entry (konzo is an exact synonym of cassavism).
📘

Definitions

1
Clinical case definition of konzo
Konzo is defined as an upper motor neuron disease presenting with abrupt-onset, symmetric, permanent spastic paraparesis of the lower limbs with sensory and genitourinary sparing, caused by chronic dietary cyanide exposure from insufficiently processed bitter cassava combined with protein/sulfur-amino-acid malnutrition.
CASE_DEFINITION Disease-level clinical case definition for konzo.
Show evidence (1 reference)
PMID:33964344 SUPPORT Other
"Konzo is a toxico-nutritional upper motor neuron disease causing a spastic paraparesis in schoolchildren and childbearing women in some African countries."
Defines konzo as a toxico-nutritional upper motor neuron disease causing spastic paraparesis, the basis of the case definition.
⚙

Pathophysiology

4
Cyanogenic Glucoside (Linamarin) and Cyanide Exposure from Bitter Cassava
The initiating exposure of konzo is high dietary intake of the cyanogenic glucoside linamarin from insufficiently processed bitter cassava roots. During digestion linamarin is hydrolysed by the enzyme linamarase to cyanohydrins, which break down to toxic cyanide, so a monotonous diet of poorly processed bitter cassava delivers a high chronic cyanide load. Epidemiological studies associate urinary linamarin and its cyanide metabolite thiocyanate with the occurrence of konzo, and outbreaks cluster geographically and seasonally with high cyanide exposure.
cyanide metabolic process GO:0019499 ↑ INCREASED
Downstream
Impaired Cyanide Detoxification with Low Sulfur Amino Acid Intake The ingested cyanide load must be detoxified, a process dependent on dietary sulfur amino acids.
Show evidence (2 references)
PMID:20510334 SUPPORT Other
"Cassava contains cyanogenic glucosides which are hydrolysed by an enzyme linamarase to produce cyanohydrins which breakdown to toxic cyanide."
Defines the linamarin -> cyanohydrin -> cyanide pathway by which bitter cassava delivers a dietary cyanide load.
PMID:9438470 SUPPORT Human Clinical
"urinary linamarin, the cyanogenic glucoside and source of cyanide in cassava, was more closely associated with the occurrence of konzo"
Field study links urinary linamarin (the cassava cyanogen) to the occurrence of konzo, anchoring linamarin/cyanide as the initiating exposure.
Impaired Cyanide Detoxification with Low Sulfur Amino Acid Intake
Cyanide is normally detoxified to thiocyanate by sulfurtransferase enzymes that require a sulfur donor supplied by dietary sulfur-containing amino acids (methionine, cysteine). In konzo-affected populations the bitter-cassava diet is protein-poor and deficient in sulfur amino acids, so a high cyanide intake is paired with low capacity to detoxify it. Children with konzo have measurably lower cyanide detoxification rates than controls, and worse nutritional status (stunting/wasting) distinguishes konzo patients from equally cyanide-exposed healthy individuals, implicating impaired detoxification and malnutrition as the decisive co-factors.
sulfur amino acid metabolic process GO:0000096 ↓ DECREASED detoxification GO:0098754 ↓ DECREASED
Downstream
Upper Motor Neuron and Corticospinal Tract Injury Inadequately detoxified cyanide and its metabolites injure upper motor neurons via excitotoxic and oxidative mechanisms.
Show evidence (3 references)
PMID:20619859 SUPPORT Other
"High cyanide consumption with low dietary sulfur intake due to almost exclusive consumption of insufficiently processed bitter cassava roots was proposed as the cause of Konzo"
States the core toxico-nutritional mechanism: high cyanide consumption with low dietary sulfur intake from bitter cassava.
PMID:27246648 SUPPORT Human Clinical
"the odds of developing konzo was reduced by 63%"
Case-control study shows higher cyanide detoxification rate is protective, supporting impaired detoxification as a determinant of konzo.
PMID:34444788 SUPPORT Human Clinical
"The only factor differentiating konzo patients from healthy individuals exposed to cyanide poisoning appeared to be their worse nutritional status."
Protein malnutrition (limiting sulfur amino acid supply for detoxification) is the factor distinguishing konzo patients from equally cyanide-exposed controls.
Upper Motor Neuron and Corticospinal Tract Injury
Inadequately detoxified cyanide and its metabolites selectively injure upper motor neurons and their corticospinal (pyramidal) tract axons, with sparing of lower motor neurons, sensory pathways, and sphincter function. Proposed effector mechanisms include excitotoxicity and oxidative stress: cyanide is a mitochondrial toxin, and cassava-cyanide metabolites (thiocyanate, cyanate) act on neurons, with cyanate inducing reactive oxygen species, caspase activation, and depolarizing currents through ionotropic glutamate receptors in spinal cord neurons.
upper motor neuron CL:0008048
glutamate receptor signaling pathway GO:0007215 ↑ INCREASED response to oxidative stress GO:0006979 ↑ INCREASED
corticospinal tract UBERON:0002707
Downstream
Symmetric Permanent Spastic Paraparesis Loss of upper motor neuron / corticospinal input produces a permanent spastic paraparesis of the legs.
Show evidence (3 references)
PMID:33964344 SUPPORT Other
"Konzo is a toxico-nutritional upper motor neuron disease causing a spastic paraparesis in schoolchildren and childbearing women in some African countries."
Characterizes konzo as a toxico-nutritional upper motor neuron disease, the anatomical/cellular target of injury.
PMID:39608576 SUPPORT In Vitro
"OCN (and SCN to a lesser extent) induced depolarizing currents in primary spinal cord neurons, through an activation of ionotropic glutamate receptors."
In vitro, the cassava-cyanide metabolite cyanate induces glutamate-receptor-mediated depolarizing currents in spinal cord neurons, an excitotoxic effector mechanism.
PMID:39608576 SUPPORT In Vitro
"konzo, a tropical spastic paraparesis due to selective upper motor neuron damage"
Confirms selective upper motor neuron damage as the lesion underlying konzo.
Symmetric Permanent Spastic Paraparesis
The clinical endpoint of konzo is an abrupt-onset, symmetric, permanent and non-progressive spastic paraparesis of the lower limbs, with upper motor neuron signs (spasticity, hyperreflexia, extensor plantar responses, clonus) and a stiff, scissoring gait, and no sensory or genitourinary impairment. Once established the deficit is irreversible.
upper motor neuron CL:0008048
neuron apoptotic process GO:0051402 ↑ INCREASED
Show evidence (2 references)
PMID:29981837 SUPPORT Other
"The main clinical picture consists of a symmetrical, permanent and irreversible spastic paraparesis (motor neuron disease) with no signs of sensory or genitourinary impairments."
Defines the konzo endpoint as a symmetrical, permanent, irreversible spastic paraparesis with sensory and genitourinary sparing.
PMID:12376882 SUPPORT Other
"Konzo is characterized by the abrupt onset of isolated and symmetric spastic paraparesis of the lower extremities which is permanent but nonprogressive."
Confirms the abrupt-onset, symmetric, permanent but nonprogressive nature of the spastic paraparesis.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Konzo Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

5
Musculoskeletal 1
Spastic paraplegia Spastic paraplegia HP:0001258
Show evidence (2 references)
PMID:29981837 SUPPORT Other
"The main clinical picture consists of a symmetrical, permanent and irreversible spastic paraparesis (motor neuron disease)"
Defines konzo by symmetrical permanent spastic paraparesis of the lower limbs.
PMID:12376882 SUPPORT Other
"isolated and symmetric spastic paraparesis of the lower extremities"
Documents the symmetric spastic paraparesis of the lower extremities characteristic of konzo.
Nervous System 1
Cognitive impairment Cognitive impairment HP:0100543
Show evidence (1 reference)
PMID:29981837 SUPPORT Other
"cognitive impairments and neurodevelopmental delays have been reported among school-aged and very young children"
Cognitive impairment and neurodevelopmental delay are reported in konzo-affected children.
Other 3
Lower limb spasticity Lower limb spasticity HP:0002061
Course: STABLE
Show evidence (1 reference)
PMID:12376882 SUPPORT Other
"symmetric spastic paraparesis of the lower extremities which is permanent but nonprogressive"
Spastic (increased-tone) paraparesis of the lower extremities, permanent and nonprogressive.
Spastic gait Spastic gait HP:0002064
Show evidence (1 reference)
PMID:20510334 SUPPORT Other
"konzo, an irreversible paralysis of the legs"
Konzo is an irreversible paralysis of the legs, manifesting as a spastic gait disturbance.
Upper motor neuron dysfunction Upper motor neuron dysfunction HP:0002493
Show evidence (1 reference)
PMID:12376882 SUPPORT Other
"consequently developing symptoms of upper motoneuron damage"
Konzo patients develop symptoms of upper motor neuron damage.
💊

Medical Actions

4
Cassava Detoxification by the Wetting Method
Action: dietary intervention Ontology label: Dietary Intervention NCIT:C15447
The wetting method removes residual cyanogens from cassava flour: the flour is wetted, spread in a thin layer in the shade (or sun) for a few hours, and used the same day, reducing total cyanide content several-fold. Community uptake has prevented new konzo cases and lowered urinary thiocyanate, making it the principal preventive intervention where bitter cassava remains a staple.
Show evidence (2 references)
PMID:22342647 SUPPORT Human Clinical
"No new konzo cases occurred"
A village-wide wetting-method intervention prevented new konzo cases over an 18-month period spanning two dry seasons.
PMID:20510334 SUPPORT Other
"we developed a simple wetting method that reduces the total cyanide content of cassava flour 3-6-fold"
Describes the wetting method that reduces cassava-flour total cyanide content 3-6-fold, the basis of prevention.
Dietary Diversification and Protein Supplementation
Action: dietary intervention Ontology label: Dietary Intervention NCIT:C15447
Diet:
Reducing exclusive reliance on bitter cassava and improving intake of protein and sulfur-containing amino acids addresses both arms of konzo pathogenesis (cyanide exposure and impaired detoxification).
Show evidence (1 reference)
PMID:20619859 SUPPORT Other
"High cyanide consumption with low dietary sulfur intake due to almost exclusive consumption of insufficiently processed bitter cassava roots was proposed as the cause of Konzo"
Identifies high cyanide intake with low dietary sulfur as the targetable nutritional cause, motivating diversification and protein supplementation.
Supportive and Rehabilitative Care
Action: supportive care Ontology label: Supportive Care NCIT:C15747
There is no cure for established konzo; care is supportive and rehabilitative, addressing the permanent motor disability with physiotherapy and assistive devices, since prevention is the only means of avoiding the disease.
Show evidence (1 reference)
PMID:29981837 SUPPORT Other
"Because there is no cure for Konzo, prevention of the disease remains of paramount importance."
There is no cure for konzo; management is supportive and prevention is paramount.
Physical Therapy and Rehabilitation
Action: physical therapy Ontology label: Physical Therapy NCIT:C15302
Physiotherapy, stretching, orthoses, and assistive devices to maintain mobility and reduce contractures in established konzo.
Show evidence (1 reference)
PMID:29981837 SUPPORT Other
"Severely affected subjects may use walking aids, but once the neurodamaging process has stabilized, the disability remains unchanged and irreversible"
Supportive/physical management (e.g., walking aids and mobility support) is the mainstay for the established, irreversible motor disability of konzo; there is no curative therapy.
🌍

Environmental Factors

3
Insufficiently processed bitter cassava overconsumption
A monotonous diet dominated by insufficiently processed bitter cassava (Manihot esculenta) is the cause of konzo. Short or shortcut processing leaves large amounts of the cyanogen linamarin in the consumed cassava, delivering a high dietary cyanide load. Outbreaks occur in cassava-dependent regions of sub-Saharan Africa (Democratic Republic of the Congo, Mozambique, Tanzania, Central African Republic, Angola, Cameroon, Zambia), chiefly among children and women of childbearing age.
Show evidence (2 references)
PMID:20619859 SUPPORT Other
"invariably associated with monotonous consumption of inadequately processed bitter cassava roots (Manihot esculenta) with very minimal protein supplementation"
Konzo is invariably associated with monotonous consumption of inadequately processed bitter cassava with minimal protein.
PMID:29981837 SUPPORT Other
"an association between outbreaks of the disease and chronic dietary reliance on insufficiently processed cyanogenic cassava"
Outbreaks are associated with chronic dietary reliance on insufficiently processed cyanogenic cassava.
Protein malnutrition with low sulfur amino acid intake
A protein-poor diet deficient in sulfur-containing amino acids accompanies the bitter-cassava diet and limits the substrate available for cyanide detoxification. Worse nutritional status (wasting and stunting) is the factor that distinguishes konzo patients from equally cyanide-exposed healthy controls.
Show evidence (2 references)
PMID:34444788 SUPPORT Human Clinical
"konzo patients had a high prevalence of both wasting (54.5%) and stunting (72.7%)"
Konzo patients show a high prevalence of wasting and stunting, indicating protein-energy malnutrition as an environmental co-factor.
PMID:34444788 SUPPORT Human Clinical
"malnutrition may be a key factor for the disease occurrence"
Malnutrition is identified as a key factor for konzo occurrence alongside cyanide poisoning.
Drought and food shortage
Epidemic outbreaks cluster during drought-provoked agricultural and social crises that force populations onto a diet of insufficiently processed bitter cassava, with shortcuts in processing that increase dietary cyanide exposure.
Show evidence (1 reference)
PMID:12376882 SUPPORT Other
"Epidemic outbreaks in subtropical and tropical regions are associated with drought-provoked agricultural and social crises rendering populations dependent on a diet of insufficiently processed bitter cassava."
Drought-provoked crises drive dependence on insufficiently processed bitter cassava, precipitating epidemic outbreaks.
🔀

Differential Diagnoses

3

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

Neurolathyrism MONDO:0043339
Overlapping Features Neurolathyrism is the closest mimic of konzo: an epidemic, abrupt-onset, symmetric upper-motor-neuron spastic paraparesis affecting young people during food shortages. It is caused by the excitatory amino acid neurotoxin beta-ODAP in grass pea (Lathyrus sativus) rather than by cassava-derived cyanide, so dietary history is the key discriminator.
Distinguishing Features
  • Causative exposure is grass pea (Lathyrus sativus) beta-ODAP, not cyanogenic bitter cassava.
  • Clinically near-identical upper-motor-neuron spastic paraparesis, so dietary history is the key discriminator.
Show evidence (1 reference)
PMID:37620067 SUPPORT Other
"Other toxic etiologies of TSP include lathyrism and fluorosis."
Lathyrism is listed alongside konzo as a distinct toxic etiology of tropical spastic paraparesis.
Tropical ataxic neuropathy
Overlapping Features Tropical ataxic neuropathy is the other major cassava-associated neurological disorder. Unlike konzo's upper-motor-neuron spastic paraparesis, it is characterized by sensory polyneuropathy, sensory ataxia, optic atrophy and sensorineural deafness, and occurs in elderly individuals.
Distinguishing Features
  • Sensory polyneuropathy and sensory ataxia, in contrast to konzo's spastic (upper motor neuron) paraparesis with sensory sparing.
  • Occurs in elderly individuals, whereas konzo predominates in children and young women.
Show evidence (1 reference)
PMID:21327546 SUPPORT Other
"TAN is characterized by sensory polyneuropathy, sensory ataxia, bilateral optic atrophy and bilateral sensori-neural deafness."
Tropical ataxic neuropathy is a sensory syndrome, distinguishing it from konzo's upper-motor-neuron spastic paraparesis.
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 konzo 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 konzo characteristically spares sensation and genitourinary function.
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 konzo (quote reproduces a spacing artifact in the source abstract).
{ }

Source YAML

click to show 
name: Konzo
creation_date: "2026-06-26T00:00:00Z"
description: >-
  Konzo (cassavism) is an acute-onset, symmetric, permanent and irreversible
  upper motor neuron disease producing spastic paraparesis of the legs, epidemic
  and endemic in cassava-dependent regions of sub-Saharan Africa. It is caused by
  sustained monotonous consumption of insufficiently processed bitter cassava
  (Manihot esculenta) containing the cyanogenic glucoside linamarin, combined with
  a protein-poor diet low in sulfur-containing amino acids; the resulting chronic
  high dietary cyanide exposure cannot be adequately detoxified, leading to
  selective injury of upper motor neurons and the corticospinal (pyramidal) tracts
  with characteristic sparing of sensory and genitourinary function. Outbreaks
  cluster during droughts and food shortages and disproportionately affect children
  and women of childbearing age. Konzo is clinically near-identical to grass-pea
  neurolathyrism (a distinct toxic spastic paraparesis) and is distinguished from
  tropical ataxic neuropathy and HTLV-1-associated tropical spastic paraparesis.
  There is no cure; management is supportive and rehabilitative, and prevention
  relies on cassava detoxification (the wetting method) and dietary diversification.
category: Environmental
disease_term:
  preferred_term: konzo
  term:
    id: MONDO:0022666
    label: cassavism
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0022666
      label: cassavism
    mapping_predicate: skos:exactMatch
    mapping_source: MONDO
    mapping_justification: Primary MONDO disease identifier for this konzo entry (konzo is an exact synonym of cassavism).
synonyms:
- Cassavism
- Mantakassa
- Epidemic spastic paraparesis
- Cassava cyanogenic poisoning
parents:
- Motor Neuron Disease
- Foodborne Disease
pathophysiology:
- name: Cyanogenic Glucoside (Linamarin) and Cyanide Exposure from Bitter Cassava
  description: >-
    The initiating exposure of konzo is high dietary intake of the cyanogenic
    glucoside linamarin from insufficiently processed bitter cassava roots. During
    digestion linamarin is hydrolysed by the enzyme linamarase to cyanohydrins,
    which break down to toxic cyanide, so a monotonous diet of poorly processed
    bitter cassava delivers a high chronic cyanide load. Epidemiological studies
    associate urinary linamarin and its cyanide metabolite thiocyanate with the
    occurrence of konzo, and outbreaks cluster geographically and seasonally with
    high cyanide exposure.
  chemical_entities:
  - preferred_term: linamarin
    term:
      id: CHEBI:16441
      label: linamarin
  - preferred_term: cyanide
    term:
      id: CHEBI:17514
      label: cyanide
  biological_processes:
  - preferred_term: cyanide metabolic process
    modifier: INCREASED
    term:
      id: GO:0019499
      label: cyanide metabolic process
  evidence:
  - reference: PMID:20510334
    reference_title: "Uptake of wetting method in Africa to reduce cyanide poisoning and konzo from cassava."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Cassava contains cyanogenic glucosides which are hydrolysed by an enzyme linamarase to produce cyanohydrins which breakdown to toxic cyanide."
    explanation: "Defines the linamarin -> cyanohydrin -> cyanide pathway by which bitter cassava delivers a dietary cyanide load."
  - reference: PMID:9438470
    reference_title: "Geographical and seasonal association between linamarin and cyanide exposure from cassava and the upper motor neurone disease konzo in former Zaire."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "urinary linamarin, the cyanogenic glucoside and source of cyanide in cassava, was more closely associated with the occurrence of konzo"
    explanation: "Field study links urinary linamarin (the cassava cyanogen) to the occurrence of konzo, anchoring linamarin/cyanide as the initiating exposure."
  downstream:
  - target: Impaired Cyanide Detoxification with Low Sulfur Amino Acid Intake
    description: The ingested cyanide load must be detoxified, a process dependent on dietary sulfur amino acids.
- name: Impaired Cyanide Detoxification with Low Sulfur Amino Acid Intake
  description: >-
    Cyanide is normally detoxified to thiocyanate by sulfurtransferase enzymes that
    require a sulfur donor supplied by dietary sulfur-containing amino acids
    (methionine, cysteine). In konzo-affected populations the bitter-cassava diet is
    protein-poor and deficient in sulfur amino acids, so a high cyanide intake is
    paired with low capacity to detoxify it. Children with konzo have measurably
    lower cyanide detoxification rates than controls, and worse nutritional status
    (stunting/wasting) distinguishes konzo patients from equally cyanide-exposed
    healthy individuals, implicating impaired detoxification and malnutrition as the
    decisive co-factors.
  biological_processes:
  - preferred_term: sulfur amino acid metabolic process
    modifier: DECREASED
    term:
      id: GO:0000096
      label: sulfur amino acid metabolic process
  - preferred_term: detoxification
    modifier: DECREASED
    term:
      id: GO:0098754
      label: detoxification
  evidence:
  - reference: PMID:20619859
    reference_title: "Etiology of Konzo, epidemic spastic paraparesis associated with cyanogenic glycosides in cassava: role of thiamine deficiency?"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "High cyanide consumption with low dietary sulfur intake due to almost exclusive consumption of insufficiently processed bitter cassava roots was proposed as the cause of Konzo"
    explanation: "States the core toxico-nutritional mechanism: high cyanide consumption with low dietary sulfur intake from bitter cassava."
  - reference: PMID:27246648
    reference_title: "Lower sulfurtransferase detoxification rates of cyanide in konzo-A tropical spastic paralysis linked to cassava cyanogenic poisoning."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the odds of developing konzo was reduced by 63%"
    explanation: "Case-control study shows higher cyanide detoxification rate is protective, supporting impaired detoxification as a determinant of konzo."
  - reference: PMID:34444788
    reference_title: "Revisiting Konzo Risk Factors in Three Areas Differently Affected by Spastic Paraparesis in Eastern Democratic Republic of the Congo Discloses a Prominent Role of the Nutritional Status-A Comparative Cross-Sectional Study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The only factor differentiating konzo patients from healthy individuals exposed to cyanide poisoning appeared to be their worse nutritional status."
    explanation: "Protein malnutrition (limiting sulfur amino acid supply for detoxification) is the factor distinguishing konzo patients from equally cyanide-exposed controls."
  downstream:
  - target: Upper Motor Neuron and Corticospinal Tract Injury
    description: Inadequately detoxified cyanide and its metabolites injure upper motor neurons via excitotoxic and oxidative mechanisms.
- name: Upper Motor Neuron and Corticospinal Tract Injury
  description: >-
    Inadequately detoxified cyanide and its metabolites selectively injure upper
    motor neurons and their corticospinal (pyramidal) tract axons, with sparing of
    lower motor neurons, sensory pathways, and sphincter function. Proposed effector
    mechanisms include excitotoxicity and oxidative stress: cyanide is a
    mitochondrial toxin, and cassava-cyanide metabolites (thiocyanate, cyanate)
    act on neurons, with cyanate inducing reactive oxygen species, caspase
    activation, and depolarizing currents through ionotropic glutamate receptors in
    spinal cord neurons.
  cell_types:
  - preferred_term: upper motor neuron
    term:
      id: CL:0008048
      label: upper motor neuron
  locations:
  - preferred_term: corticospinal tract
    term:
      id: UBERON:0002707
      label: corticospinal tract
  biological_processes:
  - preferred_term: glutamate receptor signaling pathway
    modifier: INCREASED
    term:
      id: GO:0007215
      label: glutamate receptor signaling pathway
  - preferred_term: response to oxidative stress
    modifier: INCREASED
    term:
      id: GO:0006979
      label: response to oxidative stress
  evidence:
  - reference: PMID:33964344
    reference_title: "Konzo risk factors, determinants and etiopathogenesis: What is new? A systematic review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Konzo is a toxico-nutritional upper motor neuron disease causing a spastic paraparesis in schoolchildren and childbearing women in some African countries."
    explanation: "Characterizes konzo as a toxico-nutritional upper motor neuron disease, the anatomical/cellular target of injury."
  - 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: IN_VITRO
    snippet: "OCN (and SCN to a lesser extent) induced depolarizing currents in primary spinal cord neurons, through an activation of ionotropic glutamate receptors."
    explanation: "In vitro, the cassava-cyanide metabolite cyanate induces glutamate-receptor-mediated depolarizing currents in spinal cord neurons, an excitotoxic effector mechanism."
  - 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: IN_VITRO
    snippet: "konzo, a tropical spastic paraparesis due to selective upper motor neuron damage"
    explanation: "Confirms selective upper motor neuron damage as the lesion underlying konzo."
  downstream:
  - target: Symmetric Permanent Spastic Paraparesis
    description: Loss of upper motor neuron / corticospinal input produces a permanent spastic paraparesis of the legs.
- name: Symmetric Permanent Spastic Paraparesis
  description: >-
    The clinical endpoint of konzo is an abrupt-onset, symmetric, permanent and
    non-progressive spastic paraparesis of the lower limbs, with upper motor neuron
    signs (spasticity, hyperreflexia, extensor plantar responses, clonus) and a
    stiff, scissoring gait, and no sensory or genitourinary impairment. Once
    established the deficit is irreversible.
  cell_types:
  - preferred_term: upper motor neuron
    term:
      id: CL:0008048
      label: upper motor neuron
  biological_processes:
  - preferred_term: neuron apoptotic process
    modifier: INCREASED
    term:
      id: GO:0051402
      label: neuron apoptotic process
  evidence:
  - reference: PMID:29981837
    reference_title: "Konzo: a distinct neurological disease associated with food (cassava) cyanogenic poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The main clinical picture consists of a symmetrical, permanent and irreversible spastic paraparesis (motor neuron disease) with no signs of sensory or genitourinary impairments."
    explanation: "Defines the konzo endpoint as a symmetrical, permanent, irreversible spastic paraparesis with sensory and genitourinary sparing."
  - reference: PMID:12376882
    reference_title: "[Endemic spastic paraperesis (konzo)]."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Konzo is characterized by the abrupt onset of isolated and symmetric spastic paraparesis of the lower extremities which is permanent but nonprogressive."
    explanation: "Confirms the abrupt-onset, symmetric, permanent but nonprogressive nature of the spastic paraparesis."
phenotypes:
- name: Spastic paraplegia
  category: Neurologic
  description: >-
    Bilateral, symmetric spasticity and weakness of the lower limbs is the defining
    feature of konzo, reflecting upper motor neuron / corticospinal tract injury with
    sensory sparing.
  phenotype_term:
    preferred_term: Spastic paraplegia
    term:
      id: HP:0001258
      label: Spastic paraplegia
  evidence:
  - reference: PMID:29981837
    reference_title: "Konzo: a distinct neurological disease associated with food (cassava) cyanogenic poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The main clinical picture consists of a symmetrical, permanent and irreversible spastic paraparesis (motor neuron disease)"
    explanation: "Defines konzo by symmetrical permanent spastic paraparesis of the lower limbs."
  - reference: PMID:12376882
    reference_title: "[Endemic spastic paraperesis (konzo)]."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "isolated and symmetric spastic paraparesis of the lower extremities"
    explanation: "Documents the symmetric spastic paraparesis of the lower extremities characteristic of konzo."
- name: Lower limb spasticity
  category: Neurologic
  description: Increased muscle tone in the legs producing stiffness and scissoring, an upper motor neuron sign.
  phenotype_term:
    preferred_term: Lower limb spasticity
    term:
      id: HP:0002061
      label: Lower limb spasticity
    clinical_course: STABLE
  evidence:
  - reference: PMID:12376882
    reference_title: "[Endemic spastic paraperesis (konzo)]."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "symmetric spastic paraparesis of the lower extremities which is permanent but nonprogressive"
    explanation: "Spastic (increased-tone) paraparesis of the lower extremities, permanent and nonprogressive."
- name: Spastic gait
  category: Neurologic
  description: A stiff, scissoring gait resulting from lower-limb spasticity and weakness.
  phenotype_term:
    preferred_term: Spastic gait
    term:
      id: HP:0002064
      label: Spastic gait
  evidence:
  - reference: PMID:20510334
    reference_title: "Uptake of wetting method in Africa to reduce cyanide poisoning and konzo from cassava."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "konzo, an irreversible paralysis of the legs"
    explanation: "Konzo is an irreversible paralysis of the legs, manifesting as a spastic gait disturbance."
- name: Upper motor neuron dysfunction
  category: Neurologic
  description: >-
    Konzo produces upper motor neuron signs (spasticity, hyperreflexia, extensor
    plantar responses, clonus) reflecting corticospinal tract involvement.
  phenotype_term:
    preferred_term: Upper motor neuron dysfunction
    term:
      id: HP:0002493
      label: Upper motor neuron dysfunction
  evidence:
  - reference: PMID:12376882
    reference_title: "[Endemic spastic paraperesis (konzo)]."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "consequently developing symptoms of upper motoneuron damage"
    explanation: "Konzo patients develop symptoms of upper motor neuron damage."
- category: Neurologic
  name: Cognitive impairment
  description: >-
    More recently, cognitive impairments and neurodevelopmental delays have been
    reported among konzo-affected school-aged and very young children, beyond the
    classic motor phenotype.
  phenotype_term:
    preferred_term: Cognitive impairment
    term:
      id: HP:0100543
      label: Cognitive impairment
  evidence:
  - reference: PMID:29981837
    reference_title: "Konzo: a distinct neurological disease associated with food (cassava) cyanogenic poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "cognitive impairments and neurodevelopmental delays have been reported among school-aged and very young children"
    explanation: "Cognitive impairment and neurodevelopmental delay are reported in konzo-affected children."
environmental:
- name: Insufficiently processed bitter cassava overconsumption
  description: >-
    A monotonous diet dominated by insufficiently processed bitter cassava
    (Manihot esculenta) is the cause of konzo. Short or shortcut processing leaves
    large amounts of the cyanogen linamarin in the consumed cassava, delivering a
    high dietary cyanide load. Outbreaks occur in cassava-dependent regions of
    sub-Saharan Africa (Democratic Republic of the Congo, Mozambique, Tanzania,
    Central African Republic, Angola, Cameroon, Zambia), chiefly among children and
    women of childbearing age.
  evidence:
  - reference: PMID:20619859
    reference_title: "Etiology of Konzo, epidemic spastic paraparesis associated with cyanogenic glycosides in cassava: role of thiamine deficiency?"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "invariably associated with monotonous consumption of inadequately processed bitter cassava roots (Manihot esculenta) with very minimal protein supplementation"
    explanation: "Konzo is invariably associated with monotonous consumption of inadequately processed bitter cassava with minimal protein."
  - reference: PMID:29981837
    reference_title: "Konzo: a distinct neurological disease associated with food (cassava) cyanogenic poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "an association between outbreaks of the disease and chronic dietary reliance on insufficiently processed cyanogenic cassava"
    explanation: "Outbreaks are associated with chronic dietary reliance on insufficiently processed cyanogenic cassava."
- name: Protein malnutrition with low sulfur amino acid intake
  description: >-
    A protein-poor diet deficient in sulfur-containing amino acids accompanies the
    bitter-cassava diet and limits the substrate available for cyanide
    detoxification. Worse nutritional status (wasting and stunting) is the factor
    that distinguishes konzo patients from equally cyanide-exposed healthy controls.
  evidence:
  - reference: PMID:34444788
    reference_title: "Revisiting Konzo Risk Factors in Three Areas Differently Affected by Spastic Paraparesis in Eastern Democratic Republic of the Congo Discloses a Prominent Role of the Nutritional Status-A Comparative Cross-Sectional Study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "konzo patients had a high prevalence of both wasting (54.5%) and stunting (72.7%)"
    explanation: "Konzo patients show a high prevalence of wasting and stunting, indicating protein-energy malnutrition as an environmental co-factor."
  - reference: PMID:34444788
    reference_title: "Revisiting Konzo Risk Factors in Three Areas Differently Affected by Spastic Paraparesis in Eastern Democratic Republic of the Congo Discloses a Prominent Role of the Nutritional Status-A Comparative Cross-Sectional Study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "malnutrition may be a key factor for the disease occurrence"
    explanation: "Malnutrition is identified as a key factor for konzo occurrence alongside cyanide poisoning."
- name: Drought and food shortage
  description: >-
    Epidemic outbreaks cluster during drought-provoked agricultural and social
    crises that force populations onto a diet of insufficiently processed bitter
    cassava, with shortcuts in processing that increase dietary cyanide exposure.
  evidence:
  - reference: PMID:12376882
    reference_title: "[Endemic spastic paraperesis (konzo)]."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Epidemic outbreaks in subtropical and tropical regions are associated with drought-provoked agricultural and social crises rendering populations dependent on a diet of insufficiently processed bitter cassava."
    explanation: "Drought-provoked crises drive dependence on insufficiently processed bitter cassava, precipitating epidemic outbreaks."
treatments:
- name: Cassava Detoxification by the Wetting Method
  description: >-
    The wetting method removes residual cyanogens from cassava flour: the flour is
    wetted, spread in a thin layer in the shade (or sun) for a few hours, and used
    the same day, reducing total cyanide content several-fold. Community uptake has
    prevented new konzo cases and lowered urinary thiocyanate, making it the
    principal preventive intervention where bitter cassava remains a staple.
  therapeutic_modality: BEHAVIORAL
  treatment_term:
    preferred_term: dietary intervention
    term:
      id: NCIT:C15447
      label: Dietary Intervention
  evidence:
  - reference: PMID:22342647
    reference_title: "Control of konzo in DRC using the wetting method on cassava flour."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "No new konzo cases occurred"
    explanation: "A village-wide wetting-method intervention prevented new konzo cases over an 18-month period spanning two dry seasons."
  - reference: PMID:20510334
    reference_title: "Uptake of wetting method in Africa to reduce cyanide poisoning and konzo from cassava."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "we developed a simple wetting method that reduces the total cyanide content of cassava flour 3-6-fold"
    explanation: "Describes the wetting method that reduces cassava-flour total cyanide content 3-6-fold, the basis of prevention."
- name: Dietary Diversification and Protein Supplementation
  description: >-
    Reducing exclusive reliance on bitter cassava and improving intake of protein
    and sulfur-containing amino acids addresses both arms of konzo pathogenesis
    (cyanide exposure and impaired detoxification).
  therapeutic_modality: BEHAVIORAL
  treatment_term:
    preferred_term: dietary intervention
    term:
      id: NCIT:C15447
      label: Dietary Intervention
    dietary_modifications:
    - action: RESTRICT
      description: Reduce reliance on insufficiently processed bitter cassava as the staple food.
    - action: ADD
      description: Increase protein and sulfur-amino-acid intake to support cyanide detoxification.
  evidence:
  - reference: PMID:20619859
    reference_title: "Etiology of Konzo, epidemic spastic paraparesis associated with cyanogenic glycosides in cassava: role of thiamine deficiency?"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "High cyanide consumption with low dietary sulfur intake due to almost exclusive consumption of insufficiently processed bitter cassava roots was proposed as the cause of Konzo"
    explanation: "Identifies high cyanide intake with low dietary sulfur as the targetable nutritional cause, motivating diversification and protein supplementation."
- name: Supportive and Rehabilitative Care
  description: >-
    There is no cure for established konzo; care is supportive and rehabilitative,
    addressing the permanent motor disability with physiotherapy and assistive
    devices, since prevention is the only means of avoiding the disease.
  treatment_term:
    preferred_term: supportive care
    term:
      id: NCIT:C15747
      label: Supportive Care
  evidence:
  - reference: PMID:29981837
    reference_title: "Konzo: a distinct neurological disease associated with food (cassava) cyanogenic poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Because there is no cure for Konzo, prevention of the disease remains of paramount importance."
    explanation: "There is no cure for konzo; management is supportive and prevention is paramount."
- name: Physical Therapy and Rehabilitation
  description: >-
    Physiotherapy, stretching, orthoses, and assistive devices to maintain mobility
    and reduce contractures in established konzo.
  therapeutic_modality: BEHAVIORAL
  treatment_term:
    preferred_term: physical therapy
    term:
      id: NCIT:C15302
      label: Physical Therapy
  evidence:
  - reference: PMID:29981837
    reference_title: "Konzo: a distinct neurological disease associated with food (cassava) cyanogenic poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Severely affected subjects may use walking aids, but once the neurodamaging process has stabilized, the disability remains unchanged and irreversible"
    explanation: "Supportive/physical management (e.g., walking aids and mobility support) is the mainstay for the established, irreversible motor disability of konzo; there is no curative therapy."
diagnosis:
- name: Clinical diagnosis of konzo
  description: >-
    Konzo is a clinical diagnosis based on the syndrome of abrupt-onset, symmetric,
    permanent spastic paraparesis of upper-motor-neuron type (spasticity,
    hyperreflexia, extensor plantar responses, clonus) with sparing of sensation and
    sphincter function, together with a history of sustained insufficiently processed
    bitter cassava consumption in an endemic area. Serological testing excludes
    HTLV-1; there is no confirmatory biomarker, though urinary thiocyanate documents
    cyanide exposure.
  diagnosis_term:
    preferred_term: physical examination
    term:
      id: NCIT:C20989
      label: Physical Examination
  markers: No confirmatory laboratory biomarker; urinary thiocyanate documents cyanide exposure but is not diagnostic.
  results: >-
    Symmetric upper-motor-neuron signs in the lower limbs with sensory and
    genitourinary sparing, plus a dietary history of insufficiently processed bitter
    cassava; HTLV-1 serology negative.
  evidence:
  - reference: PMID:29981837
    reference_title: "Konzo: a distinct neurological disease associated with food (cassava) cyanogenic poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "with no signs of sensory or genitourinary impairments"
    explanation: "The clinical syndrome has no sensory or genitourinary impairment, a key diagnostic feature distinguishing konzo from other myelopathies."
  - reference: PMID:29981837
    reference_title: "Konzo: a distinct neurological disease associated with food (cassava) cyanogenic poisoning."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Serological studies have ruled out the role of retroviruses such as the human lymphotropic viruses HIV-I/II or HTLV-I/II."
    explanation: "Serology excludes HTLV-1, supporting the diagnostic distinction from HTLV-1-associated tropical spastic paraparesis."
definitions:
- name: Clinical case definition of konzo
  definition_type: CASE_DEFINITION
  description: >-
    Konzo is defined as an upper motor neuron disease presenting with abrupt-onset,
    symmetric, permanent spastic paraparesis of the lower limbs with sensory and
    genitourinary sparing, caused by chronic dietary cyanide exposure from
    insufficiently processed bitter cassava combined with protein/sulfur-amino-acid
    malnutrition.
  scope: Disease-level clinical case definition for konzo.
  evidence:
  - reference: PMID:33964344
    reference_title: "Konzo risk factors, determinants and etiopathogenesis: What is new? A systematic review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Konzo is a toxico-nutritional upper motor neuron disease causing a spastic paraparesis in schoolchildren and childbearing women in some African countries."
    explanation: "Defines konzo as a toxico-nutritional upper motor neuron disease causing spastic paraparesis, the basis of the case definition."
differential_diagnoses:
- name: Neurolathyrism
  description: >-
    Neurolathyrism is the closest mimic of konzo: an epidemic, abrupt-onset,
    symmetric upper-motor-neuron spastic paraparesis affecting young people during
    food shortages. It is caused by the excitatory amino acid neurotoxin beta-ODAP in
    grass pea (Lathyrus sativus) rather than by cassava-derived cyanide, so dietary
    history is the key discriminator.
  disease_term:
    preferred_term: neurolathyrism
    term:
      id: MONDO:0043339
      label: lathyrism
  distinguishing_features:
  - Causative exposure is grass pea (Lathyrus sativus) beta-ODAP, not cyanogenic bitter cassava.
  - Clinically near-identical upper-motor-neuron spastic paraparesis, so dietary history is the key discriminator.
  evidence:
  - reference: PMID:37620067
    reference_title: "Tropical spastic paraparesis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Other toxic etiologies of TSP include lathyrism and fluorosis."
    explanation: "Lathyrism is listed alongside konzo as a distinct toxic etiology of tropical spastic paraparesis."
- name: Tropical ataxic neuropathy
  description: >-
    Tropical ataxic neuropathy is the other major cassava-associated neurological
    disorder. Unlike konzo's upper-motor-neuron spastic paraparesis, it is
    characterized by sensory polyneuropathy, sensory ataxia, optic atrophy and
    sensorineural deafness, and occurs in elderly individuals.
  distinguishing_features:
  - Sensory polyneuropathy and sensory ataxia, in contrast to konzo's spastic (upper motor neuron) paraparesis with sensory sparing.
  - Occurs in elderly individuals, whereas konzo predominates in children and young women.
  evidence:
  - reference: PMID:21327546
    reference_title: "Neurological disorders associated with cassava diet: a review of putative etiological mechanisms."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "TAN is characterized by sensory polyneuropathy, sensory ataxia, bilateral optic atrophy and bilateral sensori-neural deafness."
    explanation: "Tropical ataxic neuropathy is a sensory syndrome, distinguishing it from konzo's upper-motor-neuron spastic paraparesis."
- name: Tropical spastic paraparesis (HTLV-1 myelopathy)
  description: >-
    HTLV-1-associated myelopathy / tropical spastic paraparesis produces a chronic
    spastic paraparesis that can resemble konzo 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 konzo characteristically spares sensation and genitourinary function.
  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 konzo (quote reproduces a spacing artifact in the source abstract)."