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Mitochondrial Dna Depletion Syndrome 13

Disease Details

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Description: Mitochondrial DNA Depletion Syndrome 13 (MTDPS13) is a genetic disorder characterized by a significant reduction in mitochondrial DNA within cells, leading to severe muscle weakness, neurological impairment, and other systemic issues.
Type: Mitochondrial DNA depletion syndrome 13 (MTDPS13) is a genetic disorder characterized by a significant reduction in mitochondrial DNA in affected tissues. It follows an autosomal recessive pattern of inheritance.
Signs And Symptoms: Mitochondrial DNA Depletion Syndrome 13 (MTDPS13), also known as Thymidine Kinase 2 (TK2) deficiency, primarily affects muscle function. Signs and symptoms include:
- Progressive muscle weakness (myopathy)
- Difficulty walking
- Respiratory muscle weakness leading to breathing difficulties
- Hypotonia (reduced muscle tone)
- Exercise intolerance
- Motor developmental delay
- Feeding difficulties in infants
- Dysphagia (difficulty swallowing)

The severity and age of onset can vary, with some cases presenting in infancy and others in later childhood or adulthood.
Prognosis: Mitochondrial DNA Depletion Syndrome 13 (MTDPS13) is a severe, often fatal disorder, with both early-onset and rapidly progressing symptoms. Prognosis is typically poor, with many affected individuals experiencing multiorgan failure, muscular and neurological impairments, and a significantly reduced lifespan, often succumbing in childhood. The specific outcomes and age of onset can vary, but the overall outlook remains severe.
Onset: Mitochondrial DNA Depletion Syndrome 13 (MTDPS13) typically presents in infancy or early childhood.
Prevalence: The prevalence of mitochondrial DNA depletion syndrome 13 (MTDPS13) is not well documented, and it is considered a rare genetic disorder. Precise prevalence data are not available.
Epidemiology: Mitochondrial DNA depletion syndrome 13 (MTDPS13) is an extremely rare genetic disorder, and comprehensive epidemiological data are not available due to its rarity. The condition is typically inherited in an autosomal recessive manner, meaning that it occurs when an individual inherits two copies of a mutated gene, one from each parent. Due to its rarity, specific incidence and prevalence rates are not well-documented.
Intractability: Mitochondrial DNA depletion syndrome 13 (MTDPS13) is considered intractable. It is a severe genetic disorder characterized by significant mitochondrial dysfunction due to a reduction in mitochondrial DNA within cells. This condition typically results in progressive, often fatal symptoms, and currently, there is no cure. Treatment focuses on managing symptoms and improving quality of life rather than addressing the underlying cause.
Disease Severity: Mitochondrial DNA Depletion Syndrome 13 (MTDPS13) is characterized by severe early-onset liver dysfunction, progressive liver failure, and neurologic abnormalities. It typically presents in infancy or early childhood. Disease severity is generally high, with many affected individuals experiencing significant health challenges and reduced life expectancy.
Healthcare Professionals: Disease Ontology ID - DOID:0080131
Pathophysiology: Mitochondrial DNA depletion syndrome 13 (MTDPS13) is a genetic disorder characterized by a significant reduction in mitochondrial DNA (mtDNA) within cells, impairing cellular energy production. This syndrome is often caused by mutations in the DNA polymerase gamma (POLG) gene, which is crucial for mtDNA replication and repair. The resultant mtDNA depletion leads to deficient energy production in cells, particularly affecting organs and tissues with high energy demands, such as the muscles, liver, and brain. Symptoms can include muscle weakness, developmental delays, and seizures.
Carrier Status: Carrier status for mitochondrial DNA depletion syndrome 13 (MTDPS13), also known as MPV17-related hepatocerebral mitochondrial DNA depletion syndrome, refers to individuals who carry one copy of the mutated gene (MPV17) without showing symptoms. These carriers can pass the gene mutation to their offspring. If both parents are carriers, there is a 25% chance with each pregnancy that the child will have MTDPS13, a 50% chance the child will be a carrier, and a 25% chance the child will neither have the disease nor be a carrier.
Mechanism: Mitochondrial DNA depletion syndrome 13 (MTDPS13), also known as TK2-related mitochondrial DNA maintenance defect, is primarily caused by mutations in the TK2 (thymidine kinase 2) gene. The TK2 enzyme is essential for the salvage pathway of mitochondrial DNA synthesis. This syndrome is characterized by a significant reduction in mitochondrial DNA copy number in affected tissues.

**Mechanism:**

- **Mutations in TK2 Gene:** Mutations in the TK2 gene lead to deficient activity of thymidine kinase 2. This enzyme is crucial for the phosphorylation of thymidine and deoxycytidine, which are necessary for generating the deoxynucleotide triphosphates (dNTPs) required for mitochondrial DNA replication and repair.

**Molecular Mechanisms:**

1. **Reduction in dNTP Pools:** As TK2 function is compromised, the intracellular levels of dNTPs decrease, specifically within the mitochondria. This reduction hampers the replication and repair processes of mitochondrial DNA.

2. **Mitochondrial DNA Depletion:** Inadequate dNTP availability leads to impaired mitochondrial DNA replication, causing a significant drop in mitochondrial DNA copy number. This depletion results in mitochondrial dysfunction due to insufficient production of proteins necessary for the oxidative phosphorylation system.

3. **Impaired Cellular Energy Production:** The deficiency in oxidative phosphorylation disrupts ATP production, leading to energy deficits in tissues with high-energy demands, such as muscles and the central nervous system.

These compromised processes ultimately result in the clinical manifestations of the syndrome, which include muscle weakness, exercise intolerance, and in severe cases, multi-systemic involvement.

Understanding the molecular mechanisms underlying MTDPS13 is vital for developing targeted treatments aimed at restoring mitochondrial function and mitigating disease symptoms.
Treatment: Mitochondrial DNA Depletion Syndrome 13 (MTDPS13) currently does not have a definitive cure. Treatment focuses on managing symptoms and may include:

1. **Nutritional Support:** Ensuring adequate nutrition to manage metabolic demands.
2. **Medications:** Use of antioxidants and vitamins like Coenzyme Q10, carnitine, and B-vitamins to support mitochondrial function.
3. **Physical Therapy:** To maintain muscle function and mobility.
4. **Respiratory Support:** Interventions such as ventilators for those with breathing difficulties.
5. **Seizure Management:** Antiepileptic drugs for patients experiencing seizures.

Therapies are highly individualized based on the patient's specific symptoms and needs. Regular follow-up with a medical team specializing in mitochondrial disorders is crucial.
Compassionate Use Treatment: Mitochondrial DNA Depletion Syndrome 13 (MTDPS13) is a genetic disorder characterized by a severe reduction in mitochondrial DNA in affected tissues, leading to impaired energy production. Treatment options are currently limited, and there is no cure.

**Compassionate Use Treatment:** Known as expanded access, this allows patients with serious or life-threatening conditions to gain access to investigational medical products outside of clinical trials when no comparable or satisfactory alternative treatments are available. For MTDPS13, this could involve experimental therapies or drugs currently in the trial phase, used with appropriate regulatory approval.

**Off-label or Experimental Treatments:** Since standard treatments are not established, some approaches that have been explored include:
1. **Nucleoside Supplementation:** Supplements like deoxycytidine and deoxythymidine have been used experimentally with mixed results, as they can sometimes help restore mitochondrial DNA levels.
2. **Gene Therapy:** Experimental studies are looking into the potential of correcting the genetic defects at the cellular level, though this is still largely in research stages.
3. **Supportive Therapy:** Treatments to manage symptoms and improve quality of life, such as physical therapy, nutritional support, and medications to control seizures or other complications.

Patients interested in these options should consult with their healthcare provider to discuss potential risks and benefits.
Lifestyle Recommendations: For Mitochondrial DNA Depletion Syndrome 13 (MTDPS13), lifestyle recommendations may include:

1. **Regular Monitoring and Medical Care**: Regular consultations with a healthcare provider specialized in mitochondrial diseases to monitor disease progression and manage symptoms effectively.

2. **Balanced Nutrition**: A diet rich in essential nutrients, vitamins, and minerals to support overall health and cellular function. Specific dietary recommendations should be tailored by a dietitian.

3. **Energy Conservation**: Implementing strategies to conserve energy, such as pacing activities and taking frequent rest breaks, to manage fatigue and preserve muscle function.

4. **Physical Therapy**: Engaging in specialized physical therapy to maintain muscle strength and improve mobility, designed in consultation with a professional familiar with mitochondrial disorders.

5. **Avoiding Stressors**: Minimizing exposure to environmental and lifestyle stressors, such as extreme temperatures and infections, which can exacerbate symptoms.

6. **Medications and Supplements**: Use of medications and supplements as prescribed by a healthcare provider to manage symptoms and support mitochondrial function, which may include coenzyme Q10, B vitamins, and antioxidants.

7. **Adaptive Equipment**: Utilizing assistive devices to maintain independence and mobility, such as wheelchairs, walkers, or braces, as needed based on the severity of symptoms.

8. **Genetic Counseling**: For affected individuals and their families to understand the genetic aspects of the disease, potential risks to other family members, and reproductive options.

It is important to consult with healthcare providers to tailor these recommendations based on individual needs and the progression of the disease.
Medication: Mitochondrial DNA Depletion Syndrome 13 (MTDPS13) is a genetic disorder characterized by a significant reduction in mitochondrial DNA in affected tissues. Currently, there is no specific medication for MTDPS13. Management primarily focuses on supportive care and symptomatic treatment. This can include nutritional support, physical therapy, and possibly other interventions aimed at managing complications as they arise. Genetic counseling may also be recommended for affected families.
Repurposable Drugs: For Mitochondrial DNA Depletion Syndrome 13, based on current medical literature and research, there are no widely recognized repurposable drugs specifically for this rare genetic disorder. Treatment typically focuses on managing symptoms and supportive care.
Metabolites: Mitochondrial DNA depletion syndrome 13 (MTDPS13) is associated with a significant reduction in mitochondrial DNA content, leading to impaired energy production in affected tissues. This condition often results in severe metabolic disturbances. One of the key metabolites often affected is lactic acid, leading to lactic acidosis due to the reliance on anaerobic metabolism when mitochondrial function is compromised. Other metabolites may include elevated lactate-to-pyruvate ratios and abnormalities in amino acid and organic acid profiles, indicative of disrupted mitochondrial metabolism.
Nutraceuticals: Mitochondrial DNA depletion syndrome 13 (MTDPS13), also known as Thymidine Kinase 2 (TK2) deficiency, is a genetic disorder affecting mitochondrial function. Nutraceuticals such as antioxidants, coenzyme Q10, and certain vitamins (like B vitamins and vitamin C) are sometimes considered to support mitochondrial health, although their efficacy in treating MTDPS13 specifically is not well-established. Management typically includes supportive care tailored to the individual's symptoms and needs.
Peptides: Mitochondrial DNA depletion syndrome 13 (MTDPS13) is a severe metabolic disorder caused by mutations in the FBXL4 gene. It results in reduced mitochondrial DNA (mtDNA) copy numbers, leading to impaired energy production. Symptoms usually include developmental delay, encephalopathy, hypotonia, lactic acidosis, and failure to thrive. Unfortunately, there is no specific treatment, and management is supportive and symptomatic. The term "peptides" and "nan" do not directly relate to MTDPS13 in this context.