autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 4

Autosomal dominant progressive external ophthalmoplegia (adPEO) with mitochondrial DNA deletions 4 is a rare genetic disorder characterized by the accumulation of multiple large deletions of mtDNA in patients' tissues. This condition typically presents in adulthood, with symptoms including:

• Weakness of the external eye muscles
• Exercise intolerance
• Muscle weakness

The disease is genetically heterogeneous, meaning that it can be caused by mutations in different genes, including autosomal ANT1, C10ORF2, and POLG genes as well as multiple mitochondrial genes [2]. Mutations in the ANT1 and C10ORF2 gene account for approximately 4% and 35% of familial adPEO cases, respectively [2].

The condition is characterized by progressive weakness of the eye muscles, which can lead to impaired eye movements. In some cases, it may also be associated with other symptoms such as muscle weakness, exercise intolerance, and signs and symptoms of spinocerebellar ataxia.

It's worth noting that adPEO with mitochondrial DNA deletions 4 is a rare condition, and more research is needed to fully understand its causes and effects. However, it is generally considered to be a form of autosomal dominant progressive external ophthalmoplegia, which is characterized by multiple mitochondrial DNA deletions in skeletal muscle [7][9].

References:

[2] Lamantea et al. (2002) stated that mutations in the ANT1 and C10ORF2 gene account for approximately 4% and 35% of familial adPEO cases.

[7] Progressive external ophthalmoplegia is characterized by multiple mitochondrial DNA deletions in skeletal muscle. The most common clinical features include adult onset of weakness of the external eye muscles and exercise intolerance.

[9] Progressive external ophthalmoplegia is characterized by multiple mitochondrial DNA deletions in skeletal muscle. The most common clinical features include adult onset of weakness of the external eye muscles and exercise intolerance.

Autosomal dominant progressive external ophthalmoplegia (adPEO) with mitochondrial DNA deletions is a condition characterized by multiple symptoms, including:

• Adult onset weakness of the external eye muscles: This is one of the most common clinical features of adPEO, typically appearing in adulthood [7].
• Exercise intolerance: Individuals with adPEO often experience difficulty performing physical activities due to muscle weakness and fatigue [5].
• Ptosis (drooping eyelids): Ptosis can be a symptom of adPEO, although it is not consistently present [6].
• Bulbar dysfunction: This refers to impaired function of the muscles responsible for eye movements, leading to difficulties with eye movement and potentially causing frozen eyes without diplopia [13].
• Fatigue and muscle weakness: Additional symptoms can include general fatigue and muscle weakness, which may be exacerbated by physical activity.
• Sensorineural hearing loss: Some individuals with adPEO may experience sensorineural hearing loss, a condition affecting the inner ear's ability to transmit sound signals to the brain [15].
• Renal tubulopathy and respiratory failure: In more severe cases, adPEO can lead to multisystem involvement, including renal tubulopathy (kidney dysfunction) and respiratory failure.

It is essential to note that not all individuals with adPEO will exhibit these symptoms, and their severity can vary widely among affected people.

Autosomal dominant progressive external ophthalmoplegia (adPEO) with mitochondrial DNA deletions is a rare genetic disorder that affects the muscles responsible for eye movement. Diagnostic tests are crucial in confirming the diagnosis and ruling out other conditions.

Diagnostic Tests:

• Clinical Molecular Genetics test: This test is specifically designed to diagnose adPEO with mitochondrial DNA deletions, including autosomal dominant 4. The test uses deletion/duplication analysis and Multiplex Ligation-dependent Probe Amplification (MLPA) to detect genetic mutations.
• mtDNA next-generation sequencing in blood: This test can help identify genetic mutations in the mitochondrial DNA that may be causing adPEO with mitochondrial DNA deletions, including autosomal dominant 4.

Other Diagnostic Considerations:

• Genetic testing for POLG1 and other nuclear-encoded genes: Mutations in these genes have been associated with autosomal dominant progressive external ophthalmoplegia. Genetic testing can help identify these mutations.
• Muscle biopsy and histopathological examination: A muscle biopsy may be performed to examine the muscle tissue for signs of mitochondrial DNA deletions or other abnormalities.

References:

• Clinical Molecular Genetics test for Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 (Source [10])
• mtDNA next-generation sequencing in blood was negative, but mutations in numerous nuclear-encoded genes cause autosomal dominant progressive external ophthalmoplegia (Source [12])

Autosomal dominant progressive external ophthalmoplegia (adPEO) with mitochondrial DNA deletions is a rare and complex condition, and there is no specific drug treatment that can cure the disease. However, various treatments may be used to manage its symptoms.

Symptomatic Treatment

• Muscle weakness and fatigue: Physical therapy and exercise programs can help improve muscle strength and endurance.
• Eye movement problems: Eyeglasses or prisms may be prescribed to correct vision problems caused by eye muscle weakness.
• Other symptoms: Pain management, nutritional supplements, and other supportive care measures may be used to alleviate symptoms.

Mitochondrial-Targeting Therapies

• Coenzyme Q10 (CoQ10): This antioxidant has been shown to improve mitochondrial function in some patients with adPEO. However, its effectiveness is still being researched.
• Other antioxidants: Vitamin E and other antioxidants may also be prescribed to help protect against oxidative stress.

Experimental Treatments

• Research studies have explored the use of various experimental treatments, including:
  • Mitochondrial-targeting peptides
  • Antioxidant therapies
  • Gene therapy

It's essential to note that these experimental treatments are still in the early stages of research and may not be widely available or proven effective.

Consult a Specialist

Due to the rarity and complexity of adPEO, it is crucial to consult with a specialist, such as a neurologist or geneticist, for personalized guidance on managing symptoms and exploring treatment options. They can help determine the best course of action based on individual circumstances.

References:

• [4] Suomalainen A, Majander A, Wallin M, et al. Autosomal dominant progressive external ophthalmoplegia with multiple deletions of mtDNA: clinical, biochemical, and molecular genetic features of the 10q-linked disease. Neurology 1997;48:1244–1253.
• [9] The content has been gathered in partnership with the MONDO Disease Ontology. Please consult with a healthcare professional for medical advice and treatment.

Please keep in mind that this information is based on the search results provided, and it's essential to consult with a specialist for personalized guidance.

Autosomal dominant progressive external ophthalmoplegia (adPEO) with mitochondrial DNA deletions is a clinical syndrome that can be challenging to diagnose due to its overlapping features with other conditions. Here are some key points to consider in the differential diagnosis of adPEO:

• Mitochondrial myopathies: Other mitochondrial myopathies, such as Kearns-Sayre syndrome and chronic progressive external ophthalmoplegia (CPEO), can present with similar clinical features, including ptosis, impaired eye movements, and muscle weakness [7].
• Muscular dystrophies: Certain muscular dystrophies, like facioscapulohumeral muscular dystrophy, can also cause ptosis and impaired eye movements, making them a consideration in the differential diagnosis of adPEO [9].
• Myasthenia gravis: This autoimmune disorder can cause muscle weakness and fatigue, which may be mistaken for adPEO. However, myasthenia gravis typically presents with fluctuating symptoms and is often associated with other systemic features [8].
• Mitochondrial DNA polymerase gamma-A mutations: Mutations in the POLG gene, which encodes mitochondrial DNA polymerase gamma-A, can cause autosomal dominant or recessive progressive external ophthalmoplegia. This condition may present with similar clinical features to adPEO, including ptosis and impaired eye movements [15].
• Other mitochondrial disorders: Other mitochondrial disorders, such as MERRF syndrome and NARP syndrome, can also present with overlapping features with adPEO, including muscle weakness, fatigue, and other systemic symptoms [10].

It's essential to consider these conditions in the differential diagnosis of autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions. A comprehensive diagnostic workup, including genetic testing and imaging studies, may be necessary to confirm the diagnosis.

References:

[7] - Progressive external ophthalmoplegia (PEO) is a clinical syndrome that was defined by Lewis P. Rowland in the 1992 Handbook of Clinical Neurology by the following features: (1) progressive ptosis and impaired mobility of the eyes; (2) bilaterality; (3) affected muscles are innervated by more than one nerve; (4) pupils are ...

[8] - This article summarizes the neuro-ophthalmic features, differential diagnosis, diagnostic tools, systemic implications, and treatment options for progressive external ophthalmoplegia (PEO), a finding of mitochondrial myopathy. PEO often co-occurs with other symptoms of mitochondrial dysfunction, such as retinal degeneration, heart block, and muscle weakness.

[9] - Autosomal dominant progressive external ophthalmoplegia (adPEO), typically adult onset; other manifestations can include ptosis, bulbar dysfunction, fatigue, and muscle weakness. RRM2B autosomal recessive progressive external ophthalmoplegia (arPEO), a typically childhood-onset predominantly myopathic phenotype of PEO, ptosis, proximal muscle ...

[10] - Progressive external ophthalmoplegia is characterized by multiple mitochondrial DNA deletions in skeletal muscle. The most common clinical features include ...