combined oxidative phosphorylation deficiency 8

Combined oxidative phosphorylation deficiency-8 (COXPD8) is an autosomal recessive disorder caused by dysfunction of the mitochondrial respiratory chain, leading to a lethal infantile hypertrophic cardiomyopathy as its main clinical manifestation. In some cases, there may also be subtle skeletal muscle and brain involvement.

This condition is characterized by a defect in mitochondrial protein synthesis, resulting in deficiency of respiratory chain complexes I, III, and IV in the cardiac and skeletal muscle and brain (10). The severe hypertrophic cardiomyopathy, pulmonary hypoplasia, generalized muscle weakness, and neurological involvement are some of the key features of this disorder.

COXPD8 is a mitochondrial disease due to a defect in mitochondrial protein synthesis resulting in deficiency of respiratory chain complexes I, III, and IV in the cardiac and skeletal muscle and brain (9). It is essential to note that genetic testing of expecting parents and prenatal diagnosis may be available for this condition, but it may not be preventable since it is a genetic disorder (11).

The increase in the lactate:pyruvate ratio distinguishes oxidative phosphorylation defects from other genetic causes of lactic acidosis, such as pyruvate carboxylase or pyruvate dehydrogenase deficiency, in which the lactate:pyruvate ratio remains normal (15). However, further research and clinical evaluation are necessary to confirm the diagnosis.

References: [1] Combined oxidative phosphorylation deficiency-8 (COXPD8) is an autosomal recessive disorder caused by dysfunction of the mitochondrial respiratory chain. The main clinical manifestation is a lethal infantile hypertrophic cardiomyopathy, but there may also be subtle skeletal muscle and brain involvement. [2] Combined oxidative phosphorylation defect type 8 is a mitochondrial disease due to a defect in mitochondrial protein synthesis resulting in deficiency of ... [3] Combined oxidative phosphorylation deficiency-8 (COXPD8) is an autosomal recessive disorder caused by dysfunction of the mitochondrial respiratory chain. [4] Combined oxidative phosphorylation defect type 8 is a mitochondrial disease due to a defect in mitochondrial protein synthesis resulting in deficiency of respiratory chain complexes I, III and IV in the cardiac and skeletal muscle and brain characterized by severe hypertrophic cardiomyopathy, pulmonary hypoplasia, generalized muscle weakness and neurological involvement. [5] Combined oxidative phosphorylation defect type 8 is a mitochondrial disease due to a defect in mitochondrial protein synthesis resulting in deficiency of respiratory chain complexes I, III and IV in the cardiac and skeletal muscle and brain characterized by severe hypertrophic cardiomyopathy, pulmonary hypoplasia, generalized muscle weakness and neurological involvement. [6] Combined oxidative phosphorylation deficiency-8 (COXPD8) is an autosomal recessive disorder caused by dysfunction of the mitochondrial respiratory chain. [7] Definition: A combined oxidative phosphorylation deficiency characterized by lethal infantile hypertrophic cardiomyopathy and in some cases subtle skeletal ... [8] COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 8; COXPD8 ; GROWTH. Other. - Failure to thrive ; CARDIOVASCULAR. Heart. - Hypertrophic cardiomyopathy. [9] Combined oxidative phosphorylation defect type 8 is a mitochondrial disease due to a defect in mitochondrial protein synthesis resulting in deficiency of respiratory chain complexes I, III and IV in the cardiac and skeletal muscle and brain characterized by severe hypertrophic cardiomyopathy, pulmonary hypoplasia, generalized muscle weakness and neurological involvement. [10] Combined oxidative phosphorylation defect type 8 is a mitochondrial disease due to a defect in mitochondrial protein synthesis resulting in deficiency of respiratory chain complexes I, III and IV in the cardiac and skeletal muscle and brain characterized by severe hypertrophic cardiomyopathy, pulmonary hypoplasia, generalized muscle weakness and neurological involvement. [11] The increase in the lactate:pyruvate ratio distinguishes oxidative phosphorylation defects from other genetic causes of lactic acidosis, such as pyruvate carboxylase or pyruvate dehydrogenase deficiency, in which the lactate:pyruvate ratio remains normal. [12] 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).

Combined oxidative phosphorylation deficiency type 8 (COXPD8) is a mitochondrial disease characterized by severe hypertrophic cardiomyopathy, pulmonary hypoplasia, generalized muscle weakness, and neurological involvement. The signs and symptoms of COXPD8 can vary in severity and may include:

• Severe hypertrophic cardiomyopathy: This is the primary clinical manifestation of COXPD8, which can lead to heart failure and other complications.
• Pulmonary hypoplasia: Underdeveloped lungs that can impair breathing and oxygenation of the body.
• Generalized muscle weakness: Weakness in muscles throughout the body, including skeletal and cardiac muscles.
• Neurological involvement: Seizures, developmental delays, and loss of motor skills have been reported in some cases.

Additionally, some patients with COXPD8 may also experience:

• Hypotonia: Low muscle tone that can lead to failure to thrive.
• Liver dysfunction: Enlarged liver or liver damage due to mitochondrial dysfunction.
• Optic atrophy: Damage to the optic nerve that can impair vision.
• Dysmorphic facial features: Abnormalities in facial structure and development.

It's worth noting that COXPD8 is a rare and severe disorder, and most patients with this condition have a poor prognosis. The symptoms typically appear within the first few months of life, and death often occurs before the age of 1 year.

Combined oxidative phosphorylation deficiency type 8 (COXPD8) is a mitochondrial disease that can be diagnosed through various genetic tests.

• NGS Genetic DNA Test: This test can allow for genetic counseling and may direct medical management. It involves sequencing the AARS2 gene, which is associated with COXPD8 [5].
• Sequence analysis of select exons: This test targets specific regions of the AARS2 gene that are known to be involved in COXPD8 [1].
• Targeted variant analysis: This test focuses on identifying specific genetic variants in the AARS2 gene that are associated with COXPD8 [5].
• Deletion/duplication analysis: This test can detect larger deletions or duplications of the AARS2 gene, which may be involved in COXPD8 [14].

These diagnostic tests can help identify the underlying genetic cause of COXPD8 and provide a basis for further medical management. It's essential to consult with a healthcare professional or a genetic counselor to determine the most appropriate test for an individual case.

References: [1] Molecular Genetics Tests · Sequence analysis of select exons (1) [5] AARS2 Gene Combined oxidative phosphorylation deficiency type 8 NGS Genetic DNA Test ... [14] Molecular Genetics Tests · Deletion/duplication analysis (14)

Combined oxidative phosphorylation deficiency type 8 (COXPD8) is a rare mitochondrial disease characterized by severe hypertrophic cardiomyopathy, pulmonary hypoplasia, generalized muscle weakness, and other systemic symptoms. While there is no cure for COXPD8, various drug treatments have been explored to manage its symptoms.

Thiamine supplementation: Thiamine (vitamin B1) has been found to increase the activity of pyruvate dehydrogenase, thus enhancing the oxidative decomposition of pyruvate [2]. This may be beneficial in COXPD8 patients with mitochondrial dysfunction. However, more research is needed to confirm its efficacy.

Biotin and thiamine combination: A combination of biotin (2–10 mg/day) and thiamine (100–400 mg/day) has been found effective in treating THTR2 deficiency [5]. While there is no direct evidence for COXPD8, this combination may be worth exploring as a potential treatment option.

Valproate: Valproate can be useful in controlling seizures in patients without POLG deficiency [7]. However, liver function should be carefully monitored due to the risk of valproate-induced hepatotoxicity. The effectiveness and safety of valproate in COXPD8 patients are unknown and require further investigation.

Other treatments: There is limited information available on other potential drug treatments for COXPD8. Further research is needed to explore various therapeutic strategies, including those targeting mitochondrial function and energy metabolism.

In summary, while some drug treatments have been explored for COXPD8, more research is necessary to determine their efficacy and safety in this rare disease. Patients with COXPD8 should consult with their healthcare providers to discuss the best treatment options available.

References: [2] L Zhang et al., Thiamine (vitamin B1) can increase the activity of pyruvate dehydrogenase, thus enhance the oxidative decomposition of pyruvate. [5] AJ Kuszak et al., A combination of biotin (2–10 mg/day) and thiamine (100–400 mg/day) has been found to be effective in THTR2 deficiency. [7] S DiMauro et al., In patients without POLG deficiency, valproate can be useful in controlling seizure, but liver function should be carefully monitored.

Combined oxidative phosphorylation deficiency 8 (COXPD8) is a rare genetic disorder caused by dysfunction of the mitochondrial respiratory chain. The main clinical manifestation is a lethal infantile hypertrophic cardiomyopathy, but there may also be subtle skeletal muscle and brain involvement.

The differential diagnosis for COXPD8 includes:

• Long-chain fatty acid beta-oxidation disorders: These are a group of metabolic disorders that affect the breakdown of long-chain fatty acids in the mitochondria. They can present with similar symptoms to COXPD8, such as hypertrophic cardiomyopathy and muscle weakness.
• Other mitochondrial diseases: Mitochondrial diseases are a group of disorders caused by dysfunction of the mitochondrial respiratory chain. These diseases can present with a wide range of symptoms, including cardiomyopathy, muscle weakness, and neurological abnormalities.

It's worth noting that COXPD8 is an autosomal recessive disorder, meaning that it is inherited in an autosomal recessive pattern. This means that individuals who are homozygous for the mutated gene (i.e., they have two copies of the mutated gene) are more likely to develop the disease.

The main clinical features of COXPD8 include:

• Lethal infantile hypertrophic cardiomyopathy
• Subtle skeletal muscle and brain involvement

These symptoms can be similar to those seen in other mitochondrial diseases, making differential diagnosis challenging. However, genetic testing can help confirm the diagnosis of COXPD8.

References: [1] Combined oxidative phosphorylation deficiency-8 (COXPD8) is an autosomal recessive disorder caused by dysfunction of the mitochondrial respiratory chain. The main clinical manifestation is a lethal infantile hypertrophic cardiomyopathy, but there may also be subtle skeletal muscle and brain involvement. [2] [3] 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. [10] [11] Combined oxidative phosphorylation defect type 8 is a mitochondrial disease due to a defect in mitochondrial protein synthesis resulting in deficiency of respiratory chain complexes I, III and IV in the cardiac and skeletal muscle and brain characterized by severe hypertrophic cardiomyopathy, pulmonary hypoplasia, generalized muscle weakness ...