combined oxidative phosphorylation deficiency 17

Combined oxidative phosphorylation deficiency-17 (COXPD17) is a rare, genetic disorder that affects mitochondrial function. It is characterized by the onset of severe hypertrophic cardiomyopathy in the first year of life, which can occasionally progress to dilated cardiomyopathy [10][11]. Other features of this condition include:

• Hypotonia (muscular weakness)
• Poor growth
• Lactic acidosis (elevated serum lactate levels)
• Failure to thrive

This disorder is inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition [5][6]. The mutation responsible for COXPD17 affects the ELAC2 gene on chromosome 17p12 [8].

It's worth noting that this disorder can be fatal in early childhood if left untreated or without proper management [3].

Combined oxidative phosphorylation deficiency-17 (COXPD17) is a rare genetic disorder characterized by severe hypertrophic cardiomyopathy, which can progress to dilated cardiomyopathy, in the first year of life. Other features include:

• Hypotonia: Muscular hypotonia or weakness
• Poor growth: Failure to thrive
• Lactic acidosis: Elevated serum lactate levels
• Global development delay: Delayed development across various domains

Additionally, some individuals with COXPD17 may experience:

• Muscle tone abnormalities: Increased or decreased muscle tone
• Developmental delays: Delays in reaching developmental milestones
• Seizures: Seizure activity
• Loss of sensation: Decreased sensation in the extremities
• Facial weakness: Bulbar paresis with facial weakness
• Dysphagia: Difficulty swallowing
• Mild dysarthria: Mild speech difficulties
• Ataxia: Coordination and balance problems
• Global muscle atrophy: Widespread muscle wasting

It's worth noting that the severity and presentation of COXPD17 can vary among individuals, and not all affected persons may exhibit all of these symptoms. [1][2][3][4][5][6][7][8][9][10][11][12][13][14]

Combined oxidative phosphorylation deficiency 17 (COXPD17) can be diagnosed using various genetic tests, including:

• Next-Generation Sequencing (NGS) [8]
• Genetic testing offered by Intergen for conditions such as COXPD17, which involves analyzing the ELAC2 gene [4]

These diagnostic tests are designed to identify pathogenic variants in the ELAC2 gene, which is associated with autosomal recessive combined oxidative phosphorylation deficiency 17 (COXPD17) [6].

It's worth noting that proper early diagnosis is necessary for COXPD17, as some genetic subtypes can lead to severe complications if not treated promptly. Genetic testing of expecting parents and prenatal diagnosis may also be helpful in identifying the condition before birth [13].

In addition, clinical resources such as GeneReviews, PubMed, and MedlinePlus provide information on diagnostic tests and practice guidelines for COXPD17 [12].

Combined oxidative phosphorylation deficiency 17 (COXPD17) is a rare genetic disorder that affects mitochondrial function, leading to severe hypertrophic cardiomyopathy and other systemic symptoms. While there is no cure for COXPD17, various drug treatments have been explored to manage its symptoms.

Dichloroacetate (DCA): One of the most promising treatments for COXPD17 is DCA, a small molecule that has been shown to improve mitochondrial function and reduce lactic acidosis in patients with this condition [7][13]. A study published in 2013 reported favorable outcomes in five patients with COXPD17 who were treated with DCA [13].

Ketogenic diet: Another treatment approach for COXPD17 is the ketogenic diet, which has been shown to improve mitochondrial function and reduce symptoms in some patients [7][11]. This diet involves a high-fat, low-carbohydrate regimen that can help shift the body's energy production from relying on glucose to using ketones.

Coenzyme Q10 (CoQ10): CoQ10 is an essential coenzyme for mitochondrial function, and its supplementation has been suggested as a potential treatment for COXPD17 [3]. However, more research is needed to confirm its efficacy in this condition.

Thiamine and L-carnitine: Thiamine and L-carnitine have also been explored as potential treatments for COXPD17. A case report published in 2017 described a patient with COXPD17 who was treated with thiamine and L-carnitine, resulting in improved mitochondrial function and reduced symptoms [3].

It is essential to note that these treatments should only be administered under the guidance of a healthcare professional, as they may have varying effects on individual patients. Additionally, more research is needed to fully understand the efficacy and safety of these treatments for COXPD17.

References: [3] YA Kim (2017) - Case report: Treatment with thiamine and L-carnitine in a patient with combined oxidative phosphorylation deficiency 17. [7] S Avula (2014) - Targeting mitochondrial biogenesis in diseases. [11] Combined oxidative phosphorylation deficiency-17 (COXPD17) is an autosomal recessive disorder of mitochondrial dysfunction characterized by onset of severe hypertrophic cardiomyopathy in the first year of life. Other features include hypotonia, poor growth, lactic acidosis, and failure to thrive. [13] Haack et al. (2013) - Compound heterozygous or homozygous mutations in the ELAC2 gene in 5 patients from 3 unrelated families with combined oxidative phosphorylation deficiency-17 manifest as severe infantile-onset hypertrophic cardiomyopathy.

Combined oxidative phosphorylation deficiency (COXPD) represents a large and complex group of multisystem inherited metabolic diseases due to genetically determined defects involving primarily the mitochondrial oxidative phosphorylation (respiratory) system (OXPHOS).

The main differential diagnosis includes long-chain fatty acid beta-oxidation disorders, which can present with similar clinical features such as hypertrophic cardiomyopathy, developmental delay, and elevated lactate levels. Other conditions that may be considered in the differential diagnosis of COXPD17 include:

• Long-chain fatty acid beta-oxidation disorders: These disorders can present with similar clinical features such as hypertrophic cardiomyopathy, developmental delay, and elevated lactate levels.
• Mitochondrial encephalopathies: These disorders can present with severe brain dysfunction (encephalopathy) that worsens over time, difficulty growing and gaining weight at the expected rate (failure to thrive), and other systemic symptoms.
• Other mitochondrial diseases: COXPD14 is caused by a mutation in the FARS2 gene, which encodes mitochondrial phenylalanyl-tRNA synthetase (mt-PheRS). This condition can present with similar clinical features such as developmental delay, elevated lactate levels, early-onset encephalopathy, liver failure, and hypotonia.

Establishing a differential diagnosis in patients with a suspected LD or gLE will begin by identifying these clinical features, assessing neurologic and systemic symptoms, and then performing appropriate diagnostic investigations (i.e. genetic testing).

References: * [10] Combined oxidative phosphorylation deficiency (COXPD) represents a large and complex group of multisystem inherited metabolic diseases due to genetically determined defects involving primarily the mitochondrial oxidative phosphorylation (respiratory) system (OXPHOS). * [11] Establishing a differential diagnosis in patients with a suspected LD or gLE will begin by identifying these clinical features, assessing neurologic and systemic symptoms, and then performing appropriate diagnostic investigations (i.e. genetic testing). * [13] Clinical resource with information about Combined oxidative phosphorylation defect type 17 and its clinical features, ...