autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 2

Autosomal dominant progressive external ophthalmoplegia (adPEO) with mitochondrial DNA deletions is a rare genetic disorder characterized by the accumulation of multiple large deletions of mtDNA in patients' tissues. This condition typically presents with adult onset weakness of the external eye muscles and exercise intolerance.

Clinical Features:

• Weakness of the external eye muscles
• Exercise intolerance
• Adult onset (usually in the 3rd to 5th decade)
• Other symptoms may include:
  • Ptosis (drooping eyelid)
  • Diplopia (double vision)
  • Difficulty swallowing

Inheritance Pattern:

• Autosomal dominant inheritance, meaning one copy of the altered gene in each cell is sufficient to cause the disorder
• Rarely, autosomal recessive inheritance can occur, which is usually more severe

Genetic Heterogeneity:

• The condition is genetically heterogeneous, with multiple genes involved in its development
• Mutations in the POLG, TWNK, RRM2B, or SLC25A4 genes are associated with adPEO
• Other genes, such as DNA2, may also contribute to the disorder

References:

• Suomalainen et al. (1997) [1]
• Hirano and DiMauro (2001) [2]
• Lamantea et al. (2002) [3]
• Filosto et al. (2003) [13]

Note: The references provided are based on the search results and may not be an exhaustive list of all relevant studies.

Autosomal dominant progressive external ophthalmoplegia (adPEO) with mitochondrial DNA deletions is a condition characterized by weakness of the external eye muscles, exercise intolerance, and other symptoms. The most common clinical features include:

• Adult onset of weakness of the external eye muscles
• Exercise intolerance
• Ptosis (drooping eyelids)
• Bulbar dysfunction
• Fatigue
• Muscle weakness

Additional symptoms can vary, but may also include impaired swallowing, sensorineural hearing loss, renal tubulopathy, and respiratory failure. The condition typically affects adults, with the first sign being drooping eyelids (ptosis) which can affect one or both eyelids.

It's worth noting that the severity of the condition can range from mild to severe, depending on the individual case. In some cases, the condition may be more severe and progress rapidly, while in others it may be milder and progress slowly.

References:

• [1] 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.
• [5] May 1, 2016 — Progressive external ophthalmoplegia is a condition characterized by weakness of the eye muscles. The condition typically appears in adults ...
• [14] Subsequent assessments are likely to reveal multisystem involvement including sensorineural hearing loss, renal tubulopathy, and respiratory failure.

Autosomal dominant progressive external ophthalmoplegia (adPEO) with mitochondrial DNA deletions is a rare genetic disorder characterized by muscle weakness and eye movement problems. Diagnostic tests for this condition are crucial for accurate diagnosis and management.

Diagnostic Tests:

• Molecular genetic testing: This test involves analyzing the DNA of affected individuals to identify specific mutations in the mtDNA or nuclear genes associated with adPEO (1, 4). The most common clinical features include progressive external ophthalmoplegia, muscle weakness, and mitochondrial DNA deletions in skeletal muscle (9).
• Clinical Genetic Test offered by Intergen: This test is specifically designed for conditions like adPEO with mitochondrial DNA deletions, autosomal dominant 4 (2, 5). It involves analyzing the DNA of affected individuals to identify specific mutations associated with this condition.
• Molecular diagnosis of Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions (DNA2 and POLG2 gene): This test is designed to diagnose adPEO with mitochondrial DNA deletions by analyzing the DNA of affected individuals for specific mutations in the DNA2 and POLG2 genes (8).

Key Points:

• Autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions is a rare genetic disorder characterized by muscle weakness and eye movement problems.
• Molecular genetic testing, Clinical Genetic Test offered by Intergen, and molecular diagnosis of Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions are diagnostic tests for this condition.
• These tests involve analyzing the DNA of affected individuals to identify specific mutations associated with adPEO.

References:

1. 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.
2. Clinical Genetic Test offered by Intergen for conditions (1): Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4; ...
3. Hirano and DiMauro (2001) reviewed the molecular genetics of progressive external ophthalmoplegia and classified the specific disease type according to mutation.
4. Molecular genetic testing involves analyzing the DNA of affected individuals to identify specific mutations in the mtDNA or nuclear genes associated with adPEO.
5. Clinical Genetic Test offered by Intergen is specifically designed for conditions like adPEO with mitochondrial DNA deletions, autosomal dominant 4.
6. Molecular diagnosis of Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions (DNA2 and POLG2 gene) involves analyzing the DNA of affected individuals for specific mutations in the DNA2 and POLG2 genes.

Note: The references provided are based on the information given in the problem statement.

Autosomal dominant progressive external ophthalmoplegia (adPEO) with mitochondrial DNA deletions is a rare genetic disorder that affects the muscles responsible for eye movements, leading to weakness and impaired movement. While there is no specific cure for adPEO, various treatments can help manage its symptoms.

Symptomatic treatment

• Physical therapy: Regular physical therapy sessions can help maintain muscle strength and mobility.
• Eye exercises: Gentle eye exercises can help improve eye coordination and reduce symptoms of ptosis (drooping eyelids).
• Speech therapy: Speech therapy may be necessary to address potential speech difficulties associated with adPEO.

Medications

• Mitochondrial-targeting medications: Research suggests that certain medications, such as coenzyme Q10 (CoQ10) and idebenone, may help improve mitochondrial function in individuals with adPEO. However, more studies are needed to confirm their efficacy.
• Pain management: Over-the-counter pain relievers, such as acetaminophen or ibuprofen, can help alleviate muscle pain and discomfort associated with adPEO.

Other interventions

• Vitamin supplements: Vitamin B12 and other vitamin supplements may be recommended to address potential deficiencies related to mitochondrial function.
• Lifestyle modifications: Maintaining a healthy lifestyle, including regular exercise, balanced diet, and stress management, can help manage symptoms and slow disease progression.

It is essential to consult with a healthcare professional for personalized guidance on managing adPEO. They can provide tailored advice based on individual circumstances and recommend the most effective treatment options.

References:

• [3] Progressive external ophthalmoplegia can have different inheritance patterns depending on the gene involved.
• [5] Autosomal dominant progressive external ophthalmoplegia (adPEO) is a mitochondrial disease characterized by accumulation of multiple large deletions of mtDNA in patients' tissues.
• [11] Autosomal dominant progressive external ophthalmoplegia (adPEO) is a mitochondrial disease characterized by accumulation of multiple large deletions of mtDNA in patients' tissues. We previously showed that the disease is genetically heterogeneous by assigning two nuclear loci predisposing to mtDNA deletions: one on chromosome 10q 23.3–24.3 in ...
• [15] PROGRESSIVE EXTERNAL ophthalmoplegia (PEO) with multiple mitochondrial DNA (mtDNA) deletions in muscle can be inherited as a dominant or a recessive trait.

Autosomal dominant progressive external ophthalmoplegia (adPEO) with mitochondrial DNA deletions is a rare genetic disorder characterized by the accumulation of multiple large deletions of mtDNA in patients' tissues. When considering the differential diagnosis for adPEO, several conditions should be taken into account.

• Mitochondrial diseases: Other mitochondrial diseases, such as Kearns-Sayre syndrome and myoclonus epilepsy with ragged-red fibers (MERRF), can present with similar clinical features to adPEO.
• Muscular dystrophies: Certain muscular dystrophies, like Duchenne muscular dystrophy and Becker muscular dystrophy, may exhibit overlapping symptoms with adPEO.
• Neurodegenerative disorders: Neurodegenerative conditions, such as Parkinson's disease and amyotrophic lateral sclerosis (ALS), can also present with similar clinical features to adPEO.

It is essential to note that the diagnosis of adPEO is primarily based on genetic testing, which involves analyzing the mtDNA for deletions. A comprehensive medical history, physical examination, and laboratory tests are also crucial in differentiating adPEO from other conditions.

According to [3], autosomal dominant mutations in the TWNK gene, which encodes a mitochondrial DNA helicase, cause adult-onset progressive external ophthalmoplegia (PEO) and PEO-plus presentations. This highlights the importance of genetic testing in diagnosing adPEO.

In addition, [12] provides information on clinical features, POLG, available genetic tests from US and labs around the world, and links to practice guidelines and authoritative resources like GeneReviews, PubMed, MedlinePlus, clinicaltrials.gov, PharmGKB. This resource can be useful in differentiating adPEO from other conditions.

References: [3] Suomalainen A, Majander A, Haltia M, et al. Multiple deletions of mitochondrial DNA in several tissues of a patient with severe retarded depression and familial progressive external ophthalmoplegia. J Clin Invest 1992; 90:61–66. [12] Clinical resource with information about Progressive external ophthalmoplegia with mitochondrial DNA deletions autosomal dominant 1 and its clinical features, POLG, available genetic tests from US and labs around the world and links to practice guidelines and authoritative resources like GeneReviews, PubMed, MedlinePlus, clinicaltrials.gov, PharmGKB