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The role of mitochondria in energy production -

Mitochondria are the powerhouses of cells, generating ATP, the body's primary energy source.

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POLG mutations -

However, POLG mutations disrupt this process, leading to severe energy depletion and widespread organ dysfunction.

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What causes the disease? -

This disease is caused by mutations in the POLG gene, which affects DNA polymerase gamma, an enzyme needed to replicate mitochondrial DNA. Faulty replication results in mitochondrial failure.

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How POLG mutations affect the body -

Defective POLG disrupts mitochondrial DNA, causing cell damage and organ dysfunction, especially in high-energy tissues like the brain, muscles, and liver.

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Inheritance and genetic risks -

POLG mutations can be inherited recessively or dominantly, requiring faulty genes from one or both parents to cause symptoms.

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Symptoms -

Symptoms vary but commonly include muscle weakness, seizures, progressive neurological decline, vision and hearing loss, fatigue, and organ failure.

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The onset and progression of symptoms -

Symptoms can appear in infancy, childhood, or adulthood, with progression rates varying. Some experience rapid decline, while others have a slower disease course depending on mutation severity.

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POLG-related epilepsy -

Many patients suffer from severe, treatment-resistant epilepsy. This can lead to brain damage and significantly worsen disease prognosis.

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Muscle weakness and fatigue -

Mitochondrial dysfunction affects muscle cells, leading to progressive weakness, exercise intolerance, and fatigue. Over time, mobility may become severely limited.

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Vision and hearing loss -

Retinal degeneration and optic nerve damage can cause vision impairment or blindness. Hearing loss is also common due to nerve damage in the auditory system.

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Liver dysfunction and liver failure -

Many patients develop liver problems, liver failure, or damage from certain medications that worsen mitochondrial dysfunction.

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Gastrointestinal complications -

Patients may suffer from severe nausea, vomiting, difficulty swallowing, and gut dysmotility, which can lead to malnutrition and weight loss.

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Mental and cognitive decline -

As brain cells lose energy, patients experience memory loss, difficulty concentrating, personality changes, and, in some cases, dementia-like symptoms.

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Movement disorders and coordination issues -

Some individuals develop ataxia (poor coordination), tremors, or muscle spasms, making walking and fine motor tasks increasingly difficult.

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Cardiac complications -

Mitochondrial dysfunction can weaken heart muscles, leading to arrhythmias, cardiomyopathy, or heart failure, requiring close monitoring.

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POLG and Alpers-Huttenlocher syndrome -

A severe form of POLG disease, Alpers-Huttenlocher syndrome, primarily affects children. It causes seizures, liver failure, and rapid neurological deterioration, often leading to early death.

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Diagnosing POLG mitochondrial disease -

Diagnosis involves genetic testing, muscle biopsies, MRI scans, and metabolic tests to assess mitochondrial function and detect POLG mutations.

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The challenges of diagnosis -

Due to symptom overlap with other conditions, diagnosing POLG disease can be difficult, often requiring multiple tests and specialist evaluations.

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Treatment challenges and limitations -

There is no cure for POLG disease. Treatments focus on symptom management such as seizure control, physical therapy, and nutritional support.

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Managing epilepsy in POLG patients -

Traditional epilepsy medications may worsen symptoms. Specialized seizure management is crucial to avoid further mitochondrial damage.

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The role of diet -

Some patients benefit from a high-fat, low-carb ketogenic diet, which provides alternative energy sources for mitochondrial-deficient cells.

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Physical therapy and mobility support -

Physical therapy helps maintain mobility and muscle function, while assistive devices like wheelchairs and braces improve independence.

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Research on POLG mitochondrial disease -

Ongoing research explores gene therapy, mitochondrial-targeted treatments, and drug trials aiming to slow disease progression and improve quality of life.

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Emotional and psychological impact -

Living with POLG disease can be emotionally challenging for patients and families, requiring mental health support and counseling.

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Genetic counseling for families -

Families affected by POLG disease may benefit from genetic counseling to assess inheritance risks and explore reproductive options.

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Support groups -

Support groups provide valuable connections, information, and encouragement for those living with POLG mitochondrial disease.

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What is the life expectancy? -

Healthcare providers can assess life expectancy based on symptoms, affected organs, and health. While there’s no cure, ongoing research is working to improve understanding and treatments.

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Raising awareness of POLG mitochondrial disease -

Increased awareness can improve early diagnosis, research funding, and support for affected families, helping drive advancements in treatment.

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Living with POLG mitochondrial disease -

Despite its challenges, many patients and families find strength in support networks and adaptive therapies, striving for the best possible quality of life.

Sources: (Cleveland Clinic) (NHS) (National Institutes of Health) 

See also: How physiotherapy has shaped medical history

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