Dystonia-parkinsonism-hypermanganesemia-polycythemia and chronic liver disease is a very rare inherited disease. In this condition, a gene called SLC30A10 does not work properly. Because of this, the body cannot move extra manganese (a metal) out of the body in the normal way. Manganese builds up in the brain, blood, and liver. This build-up damages the movement centers of the brain and also the liver. People then develop dystonia (twisting muscle spasms), parkinsonism (slow, stiff movements), polycythemia (too many red blood cells), and chronic liver disease or cirrhosis.
Dystonia–parkinsonism–hypermanganesemia–polycythemia with chronic liver disease is a very rare inherited (genetic) disease. It is usually caused by harmful changes (mutations) in a gene called SLC30A10 or sometimes SLC39A14. These genes normally help the body move extra manganese out of the brain and liver. When the gene does not work, manganese builds up inside the body. This build-up damages the basal ganglia in the brain (movement control centers) and the liver. It can also make the bone marrow produce too many red blood cells, causing polycythemia (high hemoglobin / hematocrit).[
Doctors often group this disorder under the name “hypermanganesemia with dystonia, polycythemia, and cirrhosis” (HMDPC or HMNDYT1). It is passed on in an autosomal recessive way, which means a child usually gets one faulty copy of the SLC30A10 gene from each parent. Because manganese overload is the key problem, the disease is sometimes called a treatable inborn error of manganese metabolism, since removing manganese with special medicines can help many patients.
Other names
Doctors and genetic databases use several other names for this same condition. All of these point to the same basic problem of manganese overload from SLC30A10 gene changes: “hypermanganesemia with dystonia, polycythemia, and cirrhosis (HMDPC)”, “hypermanganesemia with dystonia 1”, “dystonia/parkinsonism, hypermanganesemia, polycythemia, and chronic liver disease”, and “cirrhosis-dystonia-polycythemia-hypermanganesemia syndrome.”
Some articles also call it a “syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by SLC30A10 mutations” or simply “SLC30A10-related hypermanganesemia with dystonia”. These names emphasize that the disease always links liver scarring (cirrhosis), movement problems, high red blood cell counts, and high manganese in the blood.
Types
Researchers do not use strict “Type 1 / Type 2 / Type 3” labels inside this exact SLC30A10 condition, but they see different patterns (phenotypes) in patients. These patterns are often grouped as “types” in clinical descriptions.
One type is early-onset generalized dystonia with liver disease and polycythemia. Children may start with walking problems, leg stiffness, or twisting postures in the first decade of life, and later develop enlarged liver and signs of cirrhosis.
A second type is early-onset dystonia with paraparesis (weak legs) but mild or absent liver disease. These children mainly show movement problems and high manganese, but their liver tests may stay near normal for a long time.
A third pattern is adult-onset parkinsonism with milder dystonia, where tremor, slowness, and stiffness begin later in life, and some people are misdiagnosed as having Parkinson’s disease before manganese overload is found.
Another way to think about types is by the dominant organ problem: neurologic-dominant type (mostly movement symptoms), liver-dominant type (strong cirrhosis and portal hypertension), and combined type (both strong neurologic and liver problems together). This reflects how much manganese has damaged the brain versus the liver in each person.
Causes
Although many factors can modify the disease, the main root cause is always pathogenic mutations in the SLC30A10 gene. Other “causes” below describe how these gene changes and body factors lead to the full clinical picture.
Biallelic SLC30A10 gene mutations
The core cause is having two faulty copies of the SLC30A10 gene (one from each parent). This gene makes a transporter protein that normally pumps manganese out of cells into bile so it can leave the body. When both copies are damaged, manganese builds up in blood, brain, and liver.Defective manganese export from liver cells
In healthy people, SLC30A10 helps move manganese from liver cells into bile for removal. In this disease, liver cells cannot export manganese properly, so it stays trapped inside the liver. Over years, this toxic build-up injures liver tissue and leads to chronic liver disease and cirrhosis.Manganese accumulation in brain basal ganglia
The basal ganglia are deep brain areas that control smooth movement. High manganese levels concentrate in these regions. This metal excess damages nerve cells and circuits, causing dystonia, tremor, and parkinsonism. MRI scans often show bright T1 signals in these regions, proving manganese overload.Toxic oxidative stress from manganese
Manganese in excess can produce oxidative stress (harmful reactive oxygen species) inside neurons and liver cells. Over time, this stress injures cell membranes and mitochondria, leading to cell dysfunction and death, which contributes to movement problems and liver damage.Disrupted bile excretion and cholestasis
When manganese cannot leave through bile, bile flow itself may be disturbed, and toxic materials accumulate. This cholestatic injury adds to inflammation and scarring in the liver, pushing the organ toward fibrosis and cirrhosis in many patients.Polycythemia from bone marrow response
Many patients have polycythemia (too many red blood cells). The exact mechanism is not fully clear, but it may involve chronic tissue hypoxia, altered iron handling, or direct effects of manganese on the bone marrow, which stimulate over-production of red cells.Low iron stores and iron–manganese interaction
Patients often show low iron stores (low ferritin). Iron and manganese share some transport pathways in the gut and cells. When iron is low, the body absorbs more manganese, which worsens manganese overload and disease severity.Environmental manganese exposure (diet, water, parenteral nutrition)
Even though the gene defect is primary, higher manganese intake from water, diet, or total parenteral nutrition can add to the load. Because the body cannot clear manganese well, even normal environmental exposure can push levels into a toxic range.Autosomal recessive inheritance in consanguineous families
The disease appears more often in families where parents are related (consanguineous), because both may carry the same rare SLC30A10 mutation. Having two carrier parents greatly increases the chance that a child will inherit both faulty copies.Impaired manganese handling in gut cells
SLC30A10 is also active in intestinal cells. When it fails, these cells cannot properly manage manganese, and more manganese may leak into the blood instead of being safely excreted, adding to systemic overload.Long-standing manganese deposition in cerebellum
Besides basal ganglia, manganese can collect in the cerebellum, which helps coordinate balance and fine movements. This contributes to gait unsteadiness and poor coordination in some patients.Genetic variability in SLC30A10 mutations
Different mutations (missense, nonsense, deletions) can affect the transporter in different ways. Some changes may destroy the protein completely, while others reduce its function. This variation partly explains why some patients have severe early disease and others have milder or later-onset symptoms.Secondary portal hypertension and liver scarring
As manganese damages the liver, scarring and nodules form. This can lead to portal hypertension (high pressure in the portal vein), which then causes spleen enlargement and varices. These vascular changes further worsen overall health and liver function.Neurotransmitter imbalance in movement pathways
Manganese toxicity disrupts dopamine and other neurotransmitters in the basal ganglia circuits. This imbalance mimics or overlaps with mechanisms seen in Parkinson’s disease and other movement disorders, leading to stiffness, tremor, and slow motion.Cumulative exposure over years
The disease often progresses slowly, because manganese builds up over many years. The longer the exposure, the more damage collects in brain and liver tissue, explaining why symptoms often worsen with age if the condition is not treated.Delayed diagnosis and ongoing manganese intake
Because the condition is rare and looks like other diseases (such as Wilson disease or Parkinson’s disease), it can be missed. During this delay, manganese continues to accumulate, turning a treatable situation into more advanced damage.Interaction with other manganese transporter genes
Other transporters like SLC39A14 also handle manganese. Problems in SLC30A10 plus variation in these related transporters may change how fast manganese builds up, changing the severity of disease in different people.Metabolic stress during infections or illness
Any serious illness, infection, or dehydration puts extra stress on the liver and brain. In someone with this disorder, these stresses can uncover or worsen movement problems and liver failure, acting as “triggers” for disease flares.Poor nutrition and low antioxidant intake
Inadequate nutrition, especially low intake of antioxidants (like vitamins C and E) and protein, may leave cells less able to defend against manganese-induced oxidative damage, so tissue injury worsens.Lack of chelation or iron therapy in time
Chelation medicines (that bind manganese) and iron therapy can lower manganese levels and improve symptoms. When these treatments are not started, or are stopped too early, manganese remains high and continues to harm the brain and liver.
Symptoms
Dystonia (twisting muscle spasms)
Dystonia means muscles contract in an abnormal, lasting way. In this condition, dystonia often starts in the legs or trunk and can spread to the arms, neck, and face. Children may walk on their toes or with twisted feet, and adults may have abnormal postures or painful spasms.Parkinsonism (slow and stiff movement)
Parkinsonism describes symptoms like slow movement (bradykinesia), stiffness, shuffling gait, and reduced facial expression. In SLC30A10 disease, some people, especially adults, look very similar to patients with Parkinson’s disease, but the cause is manganese toxicity, not classic Parkinson’s.Tremor
Many patients have a tremor, often in the hands or arms. The tremor may appear when they try to use their hands, such as when writing or eating. This is due to disturbed control signals in the basal ganglia and cerebellum from manganese build-up.Difficulty walking and frequent falls
Because muscles are stiff and twisted, walking becomes hard. Children may learn to walk late or lose the ability to walk without help. Adults may walk slowly, shuffle, or lose balance, which causes frequent falls and injuries.Speech problems (dysarthria)
The same movement disorder that affects the limbs also affects the muscles used for speech. Many patients have slurred or slow speech, making it hard for others to understand them. In severe cases, they may speak only a few words at a time.Swallowing difficulty (dysphagia)
Dystonia of throat and tongue muscles can cause problems with chewing and swallowing. Food may move slowly, and patients may cough or choke during meals. This increases the risk of poor nutrition and chest infections.Early motor delay in childhood
Many children with this disease sit, stand, or walk later than usual. Some may learn these skills and then lose them again as manganese builds up in the brain. Delay or regression of motor milestones is often an early clue.Joint contractures and abnormal posture
Long-lasting dystonia can lock joints in bent positions, called contractures. The spine may also curve abnormally (scoliosis). These changes can become permanent if not treated, making movement even harder.Polycythemia-related symptoms (headache, redness, tiredness)
Too many red blood cells make the blood thicker. Patients may have headaches, dizziness, flushed (red) face, and fatigue. Thick blood can also raise the risk of blood clots, which is dangerous if not treated.Enlarged liver (hepatomegaly)
Many people with this condition develop an enlarged liver, which doctors can feel under the right rib cage. Manganese accumulation and scarring cause this enlargement. Sometimes the liver is firm and uneven because of cirrhosis.Signs of chronic liver disease and cirrhosis
Over time, scarring can lead to jaundice (yellow eyes/skin), swelling of the legs or belly, easy bruising, and spider-like blood vessels on the skin. These are classic signs that liver function is failing and cirrhosis is present.Abdominal pain or discomfort
Some patients feel discomfort or pain in the upper right abdomen due to liver enlargement or congestion. Portal hypertension can also cause a feeling of fullness and sometimes enlarged spleen, which contributes to abdominal symptoms.Balance problems and unsteady gait
When manganese injures both basal ganglia and cerebellum, people can have wide-based, unsteady walking. They may veer to one side or feel unsure when turning, making daily tasks and school or work activities difficult.Cognitive or school difficulties
Some patients have trouble with attention, planning, or school performance. This may be due to a combination of brain manganese toxicity, chronic illness, fatigue, and frequent hospital visits, rather than a single cause.Psychological stress and reduced quality of life
Living with a chronic movement disorder and liver disease is stressful. Patients and families may feel anxiety, sadness, or social isolation because of visible symptoms and physical limits. These emotional problems are important symptoms that also need attention.
Diagnostic tests
Doctors use a mix of physical examination, manual bedside tests, laboratory and pathological tests, electrodiagnostic studies, and imaging to diagnose this condition and rule out other diseases.
Physical examination tests
General neurological examination
The doctor checks muscle tone, strength, reflexes, walking, and coordination. In this disease, they often find increased tone (rigidity or spasticity), abnormal postures, and problems with balance and gait, which point toward a movement disorder involving basal ganglia and cerebellum.Observation of dystonia and parkinsonism
The clinician carefully watches how the patient sits, stands, walks, and uses their hands. Twisting movements, sustained abnormal postures, shuffling steps, reduced arm swing, and masked facial expression are key signs that suggest dystonia-parkinsonism rather than simple muscle weakness.Liver and abdominal examination
The doctor feels the abdomen to check for an enlarged liver and spleen and looks for signs of chronic liver disease such as jaundice or abdominal fluid (ascites). Finding an enlarged, firm liver along with neurological signs raises suspicion for SLC30A10-related manganese disease.Vital signs and oxygen saturation
Basic checks of blood pressure, heart rate, and oxygen saturation are done. Thick blood from polycythemia can strain the heart and affect oxygen delivery. If these signs are abnormal in a person with movement problems, the doctor will look more closely for polycythemia and liver disease.
Manual (bedside) tests
Standard dystonia rating scales
Scales such as the Burke-Fahn-Marsden Dystonia Rating Scale or similar tools can be used at the bedside. The doctor scores each body part for abnormal postures and movements. A high score supports a diagnosis of generalized or segmental dystonia.Unified Parkinson’s Disease Rating Scale (UPDRS) motor exam
This manual test scores tremor, rigidity, bradykinesia, and gait. It helps document the severity of parkinsonism. An elevated UPDRS motor score in a young person with high manganese levels suggests manganese-induced parkinsonism rather than typical Parkinson’s disease.Handwriting or spiral drawing test
The patient is asked to write or draw spirals. Irregular, cramped, or tremulous writing and distorted spirals show impaired fine motor control from dystonia or parkinsonism, supporting the movement disorder diagnosis.
Laboratory and pathological tests
Whole-blood manganese level
This is a key test. People with this condition have markedly raised blood manganese. High manganese in someone with dystonia-parkinsonism, polycythemia, and liver disease is a major clue pointing to SLC30A10-related hypermanganesemia.Complete blood count (CBC) for polycythemia
A CBC checks hemoglobin, hematocrit, and red blood cell number. In this disease, these values are often high, confirming polycythemia. The CBC may also show other changes like mild anemia of chronic disease or altered platelets if liver disease is advanced.Iron studies (serum iron, ferritin, transferrin saturation)
These tests often show low iron stores, which is common in HMDPC. Low iron can increase manganese absorption. Finding low ferritin with high manganese supports the diagnosis and helps guide iron therapy as part of treatment.Liver function tests (ALT, AST, bilirubin, albumin)
Blood tests measure enzymes and proteins produced by the liver. In this disease, many patients show elevated enzymes, low albumin, or raised bilirubin, which together indicate ongoing liver injury and possible cirrhosis.Coagulation profile (prothrombin time / INR)
The liver makes clotting factors. When liver function worsens, these tests become abnormal (prolonged PRO time or high INR). This helps stage the severity of liver disease and guides decisions about treatments and surgery risk.Genetic testing for SLC30A10 mutations
Sequencing of the SLC30A10 gene confirms the diagnosis. Finding two disease-causing mutations (one from each parent) is considered the gold standard for definite diagnosis of SLC30A10-related hypermanganesemia with dystonia, polycythemia, and chronic liver disease.Liver biopsy (histology)
In selected cases, doctors may take a small sample of liver tissue. Under the microscope, they may see fibrosis, cirrhosis, and sometimes brownish deposits. Although not always required, biopsy can confirm chronic liver damage and help rule out other liver diseases.
Electrodiagnostic tests
Electromyography (EMG) of affected muscles
EMG studies can show continuous or burst-like muscle activity typical of dystonia. This supports a central movement disorder and helps distinguish it from simple weakness or peripheral nerve problems.Nerve conduction studies
These tests check how well peripheral nerves carry signals. In most patients with this condition, nerve conduction is near normal, which helps rule out peripheral neuropathy as the main cause of movement problems.
Imaging tests
Brain MRI (especially T1-weighted images)
Brain MRI is very important. In this disease, T1-weighted images often show bright signals in the basal ganglia and sometimes cerebellum due to manganese deposition. This pattern, together with high blood manganese, is strongly suggestive of SLC30A10-related disease.Liver ultrasound
Ultrasound is a simple, non-invasive test to look at liver size, texture, and blood flow. It can show hepatomegaly, nodular surface, or signs of portal hypertension such as enlarged spleen or collateral vessels, supporting the presence of chronic liver disease.Liver CT or MRI
Cross-sectional imaging gives a more detailed picture of the liver and surrounding vessels. It helps confirm cirrhosis, portal vein changes, and liver nodules, and also helps plan any procedures such as biopsy or surgery.Family screening imaging and labs
In families where one person is diagnosed, doctors may screen siblings with blood manganese tests and sometimes brain MRI. Finding similar MRI changes and raised manganese in siblings helps detect the disease early before severe symptoms develop.
Non-pharmacological treatments (therapies and other measures)
1. Manganese-restricted diet
Description: A dietitian can help remove foods and drinks that contain high manganese, such as some whole grains, nuts, tea, herbal products, and well water from deep wells. The goal is to limit extra manganese entering the body. The rest of the diet is kept balanced with enough calories, protein, vitamins, and minerals, but with controlled manganese.
Purpose: To lower manganese intake so blood and brain levels slowly fall.
Mechanism: Reduces the daily manganese load, helping chelation and the body’s own removal systems work better.[
2. Safe drinking water and environmental control
Description: Water from some wells, pipes, or industrial areas can contain high manganese. Families are advised to test water and, if needed, use bottled water or filters that remove manganese. Working or living near welding fumes or manganese-rich dust should be avoided as much as possible.
Purpose: To remove external sources of manganese exposure.
Mechanism: Less inhaled or swallowed manganese means less metal accumulation in brain and liver over time.[
3. Physical therapy for dystonia and parkinsonism
Description: A physical therapist designs stretching, strengthening, and balance exercises. Sessions are gentle and regular, with home programs to keep joints flexible and muscles as strong as possible.
Purpose: To improve mobility, posture, and safety, and to reduce contractures.
Mechanism: Movement training helps the brain and muscles work together better and compensate for damaged motor pathways.
4. Occupational therapy and daily-living training
Description: Occupational therapists teach strategies to dress, wash, write, and use tools safely, sometimes with adaptive devices like special cutlery, pens, or clothing aids.
Purpose: To maintain independence in everyday activities.
Mechanism: Breaks complex tasks into small steps and adds tools that bypass movement limitations.
5. Speech and swallowing therapy
Description: Speech-language pathologists work on speaking clearly, controlling saliva, and swallowing safely. They may recommend texture-modified foods or thickened liquids.
Purpose: To reduce choking, aspiration, and communication problems.
Mechanism: Targeted exercises support the muscles of the mouth, tongue, and throat, lowering the risk of pneumonia and malnutrition.
6. Posture, gait, and balance training
Description: Therapists practice standing, turning, and walking on different surfaces, sometimes with parallel bars or harnesses. They also teach safe ways to get up from chairs and beds.
Purpose: To reduce falls and injuries.
Mechanism: Repetitive practice strengthens core muscles and helps the brain form new balance strategies despite basal ganglia damage.
7. Use of assistive devices (walkers, wheelchairs, braces)
Description: Depending on severity, patients may use canes, walkers, wheelchairs, ankle–foot orthoses, or neck and trunk supports.
Purpose: To keep mobility safe, reduce fatigue, and prevent serious falls.
Mechanism: Mechanical support compensates for weakness, dystonia, and rigidity, allowing more stable movement.
8. Therapeutic phlebotomy (blood removal) for polycythemia
Description: Under medical supervision, small amounts of blood are removed at set intervals, similar to blood donation. This is a non-drug procedure often done in a day unit.
Purpose: To lower hematocrit and blood thickness, reducing stroke or clot risk.
Mechanism: Removing red blood cells decreases blood viscosity, easing heart and vessel workload.[
9. Liver-protective lifestyle (no alcohol, avoid toxins)
Description: Patients are advised to avoid alcohol, unnecessary herbal products, and over-the-counter drugs that can harm the liver (like high doses of paracetamol/acetaminophen).
Purpose: To slow liver scarring and reduce chances of liver failure.
Mechanism: Removing liver toxins decreases extra stress on an already injured liver.
10. Individualized nutrition plan for chronic liver disease
Description: A dietitian adjusts protein, salt, and calorie intake. In advanced liver disease, they balance enough protein to maintain muscle with limits to reduce risk of confusion (encephalopathy), and reduce salt to control fluid retention and swelling.
Purpose: To support liver function, prevent malnutrition, and control fluid build-up.
Mechanism: Carefully planned nutrition reduces metabolic burden on the liver and maintains body reserves.
11. Vaccination against hepatitis A and B
Description: Patients with chronic liver disease are usually recommended vaccines for hepatitis A and B if they are not already immune.
Purpose: To prevent additional viral liver infections that could rapidly worsen liver health.
Mechanism: Vaccines train the immune system to block these viruses, protecting the already damaged liver.[
12. Fall-prevention home modifications
Description: Families can remove loose rugs, install grab bars in bathrooms, improve lighting, and use non-slip footwear.
Purpose: To reduce fractures and head injuries from falls.
Mechanism: Environmental changes lower the chances that poor balance or dystonia will lead to serious accidents.
13. Psychological support and counseling
Description: Living with a rare chronic condition can cause sadness, anxiety, or frustration. Psychologists, social workers, or support groups can offer coping skills and emotional support.
Purpose: To protect mental health and quality of life for patients and caregivers.
Mechanism: Counseling helps people process stress, use problem-solving skills, and maintain hope and motivation.
14. Sleep hygiene and fatigue management
Description: Regular sleep times, quiet dark bedrooms, avoiding heavy meals and screens late at night, and planning rest breaks during the day are encouraged.
Purpose: To improve energy and concentration.
Mechanism: Better sleep supports brain function and can reduce perceived stiffness, pain, and mood problems.
15. School and workplace accommodations
Description: Extra exam time, flexible work hours, remote work options, special seating, and assistive technology (voice-to-text, large-key keyboards) may be arranged.
Purpose: To maintain education and employment as long as possible.
Mechanism: Adjusting goals and environment allows the person to perform tasks at their own safe pace.
16. Genetic counseling for family members
Description: Genetic counselors explain inheritance patterns, carrier testing, and family planning options.
Purpose: To help families understand their genetic risk and make informed choices.
Mechanism: Explains autosomal recessive inheritance (two faulty copies of the gene) and offers testing strategies.[
17. Regular multidisciplinary clinic follow-up
Description: Patients see neurology, hepatology, and hematology specialists regularly, often in the same clinic visit.
Purpose: To track manganese levels, liver tests, MRI findings, and blood counts.
Mechanism: Ongoing review lets doctors adjust chelation, manage complications early, and coordinate care.
18. Education and emergency plans for the family
Description: Families learn early warning signs of stroke, severe liver failure, or infection and when to go to the emergency department.
Purpose: To prevent delays in life-threatening situations.
Mechanism: Prepared families respond quickly to danger signs, improving survival and outcomes.
19. Assistive communication strategies
Description: If speech becomes hard to understand, patients may use communication boards, smartphone apps, or text-to-speech tools.
Purpose: To stay connected socially and express needs clearly.
Mechanism: Replaces or supports speech so communication remains possible even with severe dystonia.
20. Community and rare-disease support networks
Description: Joining rare-disease organizations or online groups connects families with others facing the same condition.
Purpose: To reduce isolation and share practical tips.
Mechanism: Peer support improves emotional wellbeing and offers real-world advice for daily living.
Drug treatments
⚠️ Important: All medicines below are general examples. Only a specialist doctor can decide if any of them is right or wrong for a specific patient, and what exact dose to use. Never start, stop, or change a medicine on your own.
1. Calcium disodium edetate (Calcium Disodium Versenate®)
This is a chelation drug that binds heavy metals such as lead and manganese so the kidneys can remove them. It is given by intravenous infusion in hospital. For this syndrome, it is used off-label but supported by case reports and reviews to lower manganese levels and improve neurologic symptoms and liver disease.[
Class: Chelating agent.
Dose/time (from label for heavy-metal intoxication): Typically short IV courses, dose based on weight and kidney function.
Main purpose: Lower body manganese load.
Main side effects: Kidney injury, low blood pressure, pain at injection site, low minerals; requires close monitoring.
2. Carbidopa/levodopa (e.g., Sinemet®, generic combinations)
Levodopa is converted into dopamine in the brain, and carbidopa helps more levodopa reach the brain while reducing nausea. It is a standard treatment for Parkinson’s disease and is also indicated for symptomatic parkinsonism after manganese intoxication.[
Class: Dopamine precursor with peripheral decarboxylase inhibitor.
Dose/time: Tablets taken several times daily; dose slowly increased to effect.
Purpose: Reduce slowness, stiffness, and tremor.
Side effects: Nausea, low blood pressure, hallucinations, dyskinesias (extra movements).
3. Pramipexole (Mirapex® and generics)
Pramipexole is a dopamine agonist that directly stimulates dopamine receptors. It is approved for Parkinson’s disease and sometimes used in patients who do not respond enough to levodopa or need smoother symptom control.[
Class: Non-ergot dopamine agonist.
Dose/time: Oral tablets once to three times daily, titrated slowly.
Purpose: Improve motor symptoms; may reduce levodopa dose.
Side effects: Sleepiness, sudden sleep attacks, low blood pressure, hallucinations, impulse-control problems.
4. Ropinirole (Requip® / Requip XL®)
Ropinirole is another dopamine agonist used for Parkinson’s disease. Extended-release tablets allow once-daily dosing for steadier control.[
Class: Dopamine agonist.
Dose/time: Start with low daily dose; increase gradually.
Purpose: Reduce stiffness and tremor.
Side effects: Nausea, dizziness, sleep attacks, leg swelling, hallucinations.
5. Baclofen (oral or intrathecal)
Baclofen acts on GABA-B receptors in the spinal cord to reduce muscle spasticity. In dystonia-parkinsonism, it may ease painful spasms and rigidity in some patients.[
Class: Antispasticity agent (GABA-B agonist).
Dose/time: Oral tablets several times daily; intrathecal pumps for severe cases.
Purpose: Reduce muscle stiffness and spasms.
Side effects: Drowsiness, weakness, dizziness; sudden stop can cause withdrawal.
6. Benzodiazepines (e.g., clonazepam, diazepam)
These drugs increase GABA activity in the brain, helping to calm abnormal movements and reduce anxiety linked to dystonia.
Class: Benzodiazepine anxiolytics / anticonvulsants.
Dose/time: Low oral doses at night or divided daytime doses.
Purpose: Reduce dystonic spasms, improve sleep, lessen anxiety.
Side effects: Sedation, dependence with long-term use, falls, breathing suppression with high doses or other sedatives.
7. Trihexyphenidyl or other anticholinergic agents
These medicines can reduce dystonia and tremor, especially in younger patients, by blocking acetylcholine in movement pathways.
Class: Anticholinergic antiparkinson drugs.
Dose/time: Low doses slowly increased as tolerated.
Purpose: Improve dystonia, tremor, sometimes saliva control.
Side effects: Dry mouth, blurred vision, constipation, confusion, memory problems (especially in older adults).
8. OnabotulinumtoxinA (Botox®)
Botulinum toxin injections into overactive muscles block acetylcholine release at the neuromuscular junction and are FDA-approved for dystonia such as blepharospasm and cervical dystonia.[
Class: Neuromuscular blocking toxin.
Dose/time: Local injections every 3–4 months.
Purpose: Relax specific dystonic muscles (neck, eyelids, limbs).
Side effects: Local weakness of nearby muscles, pain at injection, rare serious spread of toxin effects.
9. Tetrabenazine or deutetrabenazine
These drugs lower dopamine release by blocking VMAT2 and are used to treat involuntary movements (chorea) in Huntington’s disease. In severe hyperkinetic dystonia, they may sometimes be considered. [
Class: VMAT2 inhibitors.
Dose/time: Oral tablets in divided doses.
Purpose: Reduce jerky, uncontrolled movements.
Side effects: Depression, suicidal thoughts, parkinsonism, drowsiness; require very careful psychiatric monitoring.
10. Gabapentin or pregabalin
These medicines modulate calcium channels and lessen nerve excitability. They are sometimes used for neuropathic pain and may help burning or tingling sensations in some patients.
Class: Anticonvulsant / neuropathic pain agents.
Dose/time: Oral capsules one to three times daily.
Purpose: Reduce nerve pain, improve sleep.
Side effects: Dizziness, weight gain, swelling, drowsiness.
11. Amantadine
Amantadine increases dopamine release and has anti-glutamate effects. It can help reduce dyskinesias and may modestly improve parkinsonian symptoms.
Class: Dopaminergic / NMDA-receptor antagonist.
Dose/time: Oral, once or twice daily.
Purpose: Manage levodopa-induced extra movements and stiffness.
Side effects: Swelling of legs, skin discoloration, confusion, hallucinations.
12. Iron supplements (carefully monitored)
GeneReviews suggests that oral iron therapy, even when iron levels are not very low, can reduce blood manganese and correct polycythemia in this syndrome.[
Class: Hematinic (iron replacement).
Dose/time: Oral tablets or syrups as prescribed.
Purpose: Compete with manganese absorption and reduce polycythemia.
Side effects: Stomach upset, constipation, dark stools; overdose is dangerous.
13. Beta-blockers (e.g., propranolol)
Propranolol can help treat postural tremor and some dystonic tremors.
Class: Non-selective beta-adrenergic blocker.
Dose/time: Oral, divided doses.
Purpose: Reduce tremor and palpitations.
Side effects: Low blood pressure, slow heart rate, fatigue, worsening asthma.
14. Antiplatelet therapy (e.g., low-dose aspirin) when appropriate
In patients with significant polycythemia and vascular risk, doctors may sometimes use low-dose antiplatelet therapy to prevent clots, after carefully weighing bleeding risk.
Class: Antiplatelet agent.
Dose/time: Usually once daily.
Purpose: Reduce stroke or heart-attack risk in high-risk patients.
Side effects: Stomach irritation, bleeding risk, allergic reactions.
15. Diuretics and other liver-supportive drugs (for complications)
In advanced liver disease, diuretics like spironolactone or furosemide may be used to control fluid build-up, and medicines like lactulose can help prevent confusion from ammonia.
Class: Diuretics, osmotic laxatives.
Dose/time: Oral, dose adjusted by doctor.
Purpose: Treat ascites and hepatic encephalopathy.
Side effects: Electrolyte imbalance, dehydration, diarrhea.
16. Antiemetics and gastric protection
Nausea from dopaminergic drugs or chelators may be treated with certain anti-nausea medicines that are safer in movement disorders (avoiding dopamine-blocking drugs if possible).
Class: Antiemetics, proton pump inhibitors, H2 blockers.
Dose/time: As needed.
Purpose: Allow patients to keep taking important medicines.
Side effects: Depend on specific medicine; may include constipation, headache, or stomach changes.
17. Broad-spectrum antibiotics (for infections in advanced disease)
Because advanced liver disease and disability increase infection risk, antibiotics may be life-saving when infections occur.
Class: Antibacterial agents.
Dose/time: Short courses tailored to infection.
Purpose: Treat pneumonia, urinary infections, or sepsis promptly.
Side effects: Diarrhea, allergic reactions, resistance with over-use.
18. Antidepressants (SSRIs or others) when needed
Depression is common in chronic neurological disease and may be worsened by some movement medicines. Antidepressants can help mood and quality of life.
Class: Selective serotonin reuptake inhibitors or other antidepressants.
Dose/time: Once or twice daily, long-term.
Purpose: Treat depression and anxiety.
Side effects: Nausea, sleep changes, sexual side effects; rare suicidal thoughts early in treatment, so close monitoring is essential.
19. Vitamin K and other clotting support in severe liver disease
If blood clotting is poor due to advanced cirrhosis, vitamin K or blood products may be given before procedures.
Class: Vitamin/coagulation support.
Dose/time: Short courses as indicated.
Purpose: Reduce bleeding risk.
Side effects: Injection-site reactions; blood products carry small infection/allergy risks.
20. Emerging or off-label manganese chelators (research use)
Some centers may explore other chelators or combination treatments in clinical trials to better remove manganese while protecting organs.
Class: Experimental chelating or metal-binding drugs.
Dose/time: Only in research settings.
Purpose: Improve removal of manganese with fewer side effects.
Side effects: Unknown; carefully watched in studies.
Dietary molecular supplements
⚠️ Supplements can interact with medicines and liver disease. Always ask the treating team before using any supplement.
1. Antioxidant vitamins (C and E)
Oxidative stress plays a role in metal-related brain and liver damage. Antioxidant vitamins may help neutralize free radicals.
Dose: Often low–moderate doses once daily if doctor approves.
Function/mechanism: Donate electrons to free radicals, potentially reducing cell damage in liver and brain.
2. Vitamin B complex (especially B1, B6, B12, folate)
These vitamins support nerve health and blood cell production.
Function: Help make neurotransmitters and DNA, and support myelin.
Mechanism: Work as co-factors in many metabolic reactions vital for neurons and marrow.
3. Vitamin D
Patients with chronic liver disease and limited mobility often have low vitamin D and weak bones.
Function: Improves calcium absorption and bone health.
Mechanism: Acts on gut and bone cells to strengthen the skeleton and lower fracture risk.
4. Omega-3 fatty acids (fish oil)
Omega-3 fats have anti-inflammatory effects and may support heart and brain health.
Function: Reduce inflammation and may help mood.
Mechanism: Change cell membrane composition and inflammatory mediator production.
5. Zinc (carefully monitored)
Zinc is important for many enzymes and immune function. In some liver conditions, low zinc is common.
Function: Supports detox enzymes and immunity.
Mechanism: Acts as a cofactor in many liver and brain enzymes; must be balanced so it does not disturb copper or other metals.
6. Selenium
Selenium is part of antioxidant enzymes like glutathione peroxidase.
Function: Protects cells from oxidative injury.
Mechanism: Helps enzymes break down harmful peroxides and free radicals.
7. L-carnitine
L-carnitine helps transport fatty acids into mitochondria for energy production and may reduce fatigue.
Function: Support energy metabolism and muscle function.
Mechanism: Helps cells burn fat for fuel, possibly improving energy in weak patients.
8. N-acetylcysteine (NAC)
NAC is a precursor for glutathione, the main antioxidant in the liver.
Function: Support liver detox pathways.
Mechanism: Boosts glutathione levels, helping cells handle toxins and oxidative stress.
9. Probiotics
Healthy gut bacteria may reduce toxin production and improve bowel health, which is important in liver disease.
Function: Support gut barrier and lower ammonia-producing bacteria.
Mechanism: Compete with harmful microbes and improve gut-immune balance.
10. Protein supplements (if under-nourished)
Some patients struggle to eat enough. Special liver-friendly protein supplements can help maintain muscle.
Function: Prevent muscle wasting and weakness.
Mechanism: Provide essential amino acids without excessive volume, supporting repair and immune function.
Immunity-booster / regenerative / stem-cell-related approaches
⚠️ There are no standard, widely approved stem-cell drugs specifically for this syndrome yet. The methods below are general concepts that may be used in selected cases or research.
1. Vaccinations (routine and special)
Keeping up-to-date vaccines (influenza, COVID-19, pneumonia, hepatitis) strengthens protection against infections, especially with liver disease and disability.
Dose: As per national immunization schedule.
Mechanism: Trains the immune system to recognize and quickly attack specific germs.
2. Nutritional immune support (adequate protein, vitamins, minerals)
Rather than “magic” pills, good overall nutrition is the biggest immune booster. Adequate protein and micronutrients support white blood cell production.
Mechanism: Provides raw materials for immune cell growth and antibody production.
3. Growth factors (e.g., G-CSF in special cases)
Granulocyte colony-stimulating factor can raise white blood cell counts in severe neutropenia from other causes. In this syndrome, it would only be used if there is a separate marrow problem.
Mechanism: Stimulates bone marrow to produce more neutrophils.
4. Hepatoprotective strategies and possible regenerative trials
Some centers may use hepatoprotective drugs and enroll eligible patients in trials of therapies aimed at slowing fibrosis or regenerating liver tissue.
Mechanism: Target inflammatory and fibrotic pathways to preserve liver cells.
5. Bone-marrow or stem-cell transplant (experimental/rare)
In theory, transplanting healthy stem cells might correct some genetic disorders, but for this specific disease it is still experimental, rare, and very high risk.
Mechanism: Replace defective marrow cells with donor cells carrying normal genes.
6. Future gene therapy (research stage)
Research is exploring gene-replacement or gene-editing techniques for monogenic disorders like SLC30A10 mutations. This is not yet standard care but may become an option in the future.
Mechanism: Correct or replace the faulty gene so manganese transport normalizes.
Surgeries and procedures
1. Port or central line insertion for repeated chelation
Patients needing frequent IV calcium disodium edetate may have a small device (port) placed under the skin to make infusions easier.
Why done: To reduce repeated needle sticks and protect veins.
Procedure: Minor surgery under local or general anesthesia.
2. Deep brain stimulation (DBS)
DBS places electrodes in specific brain areas linked to movement control. It can help some severe dystonia or parkinsonism not responding to medicines.
Why done: To improve motor symptoms and reduce disabling dystonia.
Procedure: Neurosurgery with implanted electrodes and a chest battery.
3. Liver transplantation
If chronic liver disease progresses to end-stage cirrhosis or liver failure, transplant may be considered in highly selected patients.
Why done: To replace irreversible damaged liver and restore liver function.
Procedure: Major operation using a donor liver, followed by lifelong immunosuppression.
4. Endoscopic or surgical treatment of varices
Advanced liver disease may cause enlarged veins in the esophagus or stomach (varices) that can bleed. Banding or injections can reduce bleeding risk.
Why done: To prevent or control life-threatening bleeding.
Procedure: Endoscopy with banding or sclerotherapy; sometimes surgical shunts.
5. Orthopedic procedures for severe contractures or deformities
Long-standing dystonia may twist joints or cause fixed contractures.
Why done: To relieve pain, improve seating or walking, and make care easier.
Procedure: Tendon-lengthening, joint release, or spine surgery, tailored to the patient.
Key prevention strategies
Early diagnosis in at-risk families with genetic testing.
Manganese-safe environment (tested water, avoid welding fumes and high-Mn supplements).
Regular specialist follow-up to adjust chelation and medicines.
Good control of polycythemia with phlebotomy and iron therapy if indicated.
Protect the liver: no alcohol, cautious drug and herbal use.
Vaccinate against liver-related viruses (hepatitis A and B).
Fall prevention by home safety changes and assistive devices.
Infection prevention with hand hygiene and prompt treatment of fevers.
Healthy weight, activity, and diet to support heart and liver.
Psychological and social support to prevent burnout and depression that can worsen outcomes.
When to see doctors (or emergency care)
A person with this condition should see their specialist team regularly, even when feeling stable. Immediate medical care is needed if there is:
Sudden severe weakness, speech trouble, face drooping, or vision loss (possible stroke).
New or rapidly worsening jaundice, abdominal swelling, confusion, or heavy bleeding (possible liver failure).
High fever, shortness of breath, chest pain, or very fast heart rate (possible infection or clot).
Very severe or new movement problems, falls with injury, or inability to swallow safely.
Parents or caregivers should have clear written instructions from the care team on when to call clinic, when to go to emergency, and which hospital is best prepared for this rare disorder.
Simple ideas on what to eat and what to avoid
Diet must always be adjusted by a dietitian and doctor, especially with liver disease.
1. Focus on balanced, home-cooked meals
Choose simple meals with vegetables, fruits, moderate protein, and whole grains that are not extremely high in manganese. Avoid ultra-processed foods and sugary drinks.
2. Choose protein wisely
Lean meats, fish, eggs, and dairy give important protein. In advanced liver disease, the dietitian may suggest spreading protein in small amounts across the day.
3. Prefer safe water sources
Use water that has been tested for manganese or filtered as recommended by local authorities or doctors.
4. Limit very high-manganese foods
Some nuts, tea, certain grains, and high-dose manganese supplements should be limited if advised, to reduce metal intake.
5. Plenty of fruits and vegetables
Colorful fruits and vegetables give antioxidants, vitamins, and fiber that support liver and heart health.
6. Reduce salt intake
Too much salt can worsen swelling and fluid retention in liver disease. Avoid very salty snacks, instant noodles, and processed meats.
7. Avoid alcohol completely
Alcohol can speed up liver damage. For this condition, it is safest to avoid it fully.
8. Be careful with herbal products
Some herbs and “detox” products may contain manganese or other liver toxins. Always check with the doctor before using them.
9. Keep regular meals and snacks
Small, frequent meals can reduce fatigue and help maintain body weight, especially if appetite is poor.
10. Watch for signs of poor tolerance
If a food seems to worsen confusion, swelling, or bowel habits, report it to the care team so the diet can be adjusted.
Frequently asked questions (FAQs)
1. Is this disease curable?
At present, the disease is not fully curable, because the underlying gene defect remains. However, early diagnosis, chelation therapy, manganese restriction, and good supportive care can greatly improve symptoms, delay progression, and protect the liver in many patients.[
2. How important is chelation therapy?
Chelation with calcium disodium edetate is one of the most important treatments. It can lower blood manganese, improve dystonia and parkinsonism, and stabilize liver disease if started early and done safely under specialist supervision.[
3. Will all patients need liver transplantation?
No. Many patients improve or stabilize with chelation and good liver care. Transplant is reserved for those with end-stage liver failure where other options no longer work, and only after careful discussion of risks and benefits.
4. Can normal Parkinson’s medicines help?
Yes, drugs like carbidopa/levodopa, pramipexole, and ropinirole—originally for Parkinson’s disease—may improve slowness and stiffness linked to manganese-related parkinsonism, but responses vary and doses must be carefully adjusted.[
5. Is this condition always inherited?
Most reported cases are autosomal recessive genetic disorders, meaning both gene copies are affected. Parents are often healthy carriers with one faulty gene copy.[
6. Can brothers and sisters be tested?
Yes. Siblings and sometimes extended family members can have genetic testing and blood manganese measurements to see if they are affected or carriers, especially in high-risk families.
7. Does diet alone fix the problem?
Diet helps by reducing manganese intake but cannot fully correct the metal build-up once it is severe. Diet works best when combined with chelation and other treatments.
8. How often are check-ups needed?
In active treatment, patients usually need regular visits (for example every 3–6 months, or more often when adjusting chelation). Doctors check blood counts, manganese, liver function, and sometimes MRI scans.
9. Can children go to normal school?
Many children can attend school with special supports, such as extra time, physical aids, and understanding teachers. Early therapy and accommodations make a big difference in participation.
10. Are vaccines safe in this disease?
Yes, routine vaccines are generally recommended and important, especially those protecting the lungs and liver, unless there is a special medical reason to delay them. Always follow the specialist’s advice.
11. What is the long-term outlook (prognosis)?
The outlook is better when diagnosis and chelation start early, before severe brain and liver damage occur. If treatment is delayed, there may be permanent disability or liver failure, but supportive care still helps comfort and quality of life.[
12. Can physical therapy really help if the brain is damaged?
Yes. Even with brain injury, neuroplasticity allows other pathways to partly take over. Regular, gentle therapy helps maintain strength, flexibility, and safe movement, reducing complications like contractures and falls.
13. Do all patients develop polycythemia?
Polycythemia is common but not universal. Some patients mainly show movement and liver problems. Regular blood tests help detect polycythemia early so it can be treated.
14. Is pregnancy possible with this condition?
This is a complex question. Pregnancy may increase strain on the liver and heart, and some medicines used to treat the condition are unsafe in pregnancy. People should have pre-pregnancy counseling with specialists to understand risks and plan safely.
15. What can families do today to help?
Families can keep appointments, ensure chelation and medicines are taken correctly, support a manganese-safe environment, encourage gentle physical activity, eat a liver-friendly diet, and stay in close contact with the care team. Emotional support and advocacy for services (school, benefits, rehabilitation) are also very important.
Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.
The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: January 26, 2025.
