DYSTONIA PARKINSONISM

Disease

Brief Summary

Sex-linked recessive Dystonia Parkinsonism (XDP) or Dystonia of Panay is a heritable genetic disorder that causes those afflicted to exhibit dystonia (Repeated involuntary contraction of muscles), wherein control over one’s own body is severely hampered as well as late-onset XDP the dystonia is replaced by Parkinsonism and often times do not survive late-onset stage of this condition.

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People affected by Dystonia Parkinsonism

Frequency

There is a prevalence rate of 0.31 per 100,000 in the Philippines, with majority reported from the Panay islands. There have been 810 instances of XDP reported.

Inheritance

Dystonia Parkinsonism (XDP) is inherited in a X-linked recessive pattern.

Brief Summary

History of Disease

The genetic mutation that causes this disease is presumed to have originated from the native inhabitants of Panay Island in the Philippines 2000 or so years ago. The disorder goes under the local name of “Lubag" and has existed in the population Panay ever since. The disorder was first discovered by Western medicine in the 1970s, when Dr. GH Viterbo, of Roxas City, Capiz (a province of Panay) referred five of the six cases he was handling and labelled all as “dystonia musculorum deformans” to the neurology section of the Philippine General Hospital. This initiated an epidemiological survey, which resulted in the first paper published in 1976. And in 1991 XDP’s phenotype was officially described as a movement disorder, which manifests primarily as dystonia in combination with Parkinsonis.

History of Disease

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Pathogenesis

Achondroplasia is caused by a mutation in the FGF3 gene in chromosome 4 at 4p 16.3. This mutation causes a decreased production of fibroblast growth factor receptor 3 which is crucial in the conversion of cartilage into bone which is vital in the proper development of a person. This mutation is inherited in an autosomal dominant manner. More than 80 percent of people with achondroplasia have parents with normal characteristics and are born with achondroplasia due to a recent (de novo) gene modification (mutation).

Pathogenesis

Sex linked recessive dystonia parkinsonism is an recessive X-linked genetic disorder that is causesd by a mutation on the X chromosome. The XDP gene is found around < 350 kb locus in the DXS 7117–DXS 559 region of the X chromosome. This causes a reduced production of DYT3 and TAF1 which disturbs communication between muscles and the brain. Approximately 95% of those affected with this disease are male and all those afflicted with the disease have family relations from the island of Panay in the Philippines.

The illustration below shows how the gene is passed down from parent to child. Because this disease is an X-linked recessive disorder it is very rare for females to ever be affected by the disease as they must inherit two affected X chromosomes one from both parents, in contrast with males as they can only carry one X chromosome making them more likely to inherit an affected X chromosome from either an affected father, or an affected or carrier mother. This explains the large disparity between genders in regards to XDP.

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Mode of inheritance of Dystonia Parkinsonism

Symptoms

dystonia

parkinsonism and bradykinesia

tremor

rigidity

Social Concerns

XDP is a disease that permanently impacts the lives of those affected. People suffering from XDP may grow depressed and frustrated at their own condition as they gradually lose function and faculties of their body. Furthermore, the patient will lose the ability to partake in many activities, non strenuous or otherwise due to the lack of control over their own bodies. The increasing difficulty and slurring of words makes communicating difficult. This in turn makes them very heavily dependent on family members for their care and this can cause a lot of stress as the cost of treatment and care for a person suffering from XDP quickly adds up overtime as the person needs extensive care and attention. XDP is a disease that normally manifests in the late 30s of an individual. At that age the person may have had children and this is also a point of concern for the person affected because on top of the emotional strain caused by this degenerative disorder a sense of guilt and anxiety may happen as the thought of them passing on disease to their children being a grim possibility.

Treatment

There is no known cure to XDP, the treatment options for XDP are centered around managing the symptoms and increasing the quality of life of the person affected with XDP.

Botulinum Toxin Injections:

In severe cases of XDP, an injection of Botulinum toxin may be given to stop excessive muscle contraction and locking and to return the area to a relaxed state. However, the toxin permanently causes paralysis in the localized injection zone so it is only used in the later stages of the disorder wherein the dystonia has become unbearable and detrimental to the patient.

Dopamine agonist therapy

This treatment involves the use of Dopamine agonists which work by imitating dopamine in the body. This in turn might increase the strength of nerve signaling and may restore partial control over certain areas of the body locked up by dystonia or rigidity.

Other Treatment Products

The majority of these medications work more

as a depressor to lower muscle activity of the

patient and oftentimes puts the patient into

a deep sleep however upon waking the

dystonia is known to be more violent and

severe for the first few minutes upon

awakening.

Klonopin®
Zolpidem
Tetrabenazine
Clonazepam
Benzodiazepines

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Treatment for Dystonia Parkinsonism

Clinical Trials

Title:

MINGO Supplemental Trial in X-linked Dystonia Parkinsonism Patients: A Prospective Randomized, Open-labeled, Parallel Group Trial

Intervention Phase:

The study assesses the effectiveness of MINGO, a dietary supplement from local ingredients: moringa, rice, and mung beans on diagnosed X-linked dystonia parkinsonism adult patients.

Procedure:

X-linked dystonia parkinsonism adult patients are randomly assigned to two treatments: experimental and control. The experimental group takes six sachets of 20oz MINGO dietary supplement per day for 12 weeks in addition to their regular diet, while the control group will keep their normal diet.

Goal:

The primary objective of the study is to determine effectiveness of MINGO as a dietary supplement in increasing the body weight of patients through their body mass index, to improve the medical care and wellbeing of X-linked dystonia parkinsonism patients.

Further details at:

https://clinicaltrials.gov/ct2/show/study/NCT03019458

Clinical Trials

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