combined oxidative phosphorylation deficiency 48

Combined oxidative phosphorylation deficiency (COXPD) is a group of multisystem disorders with variable manifestations resulting from a defect in the mitochondrial respiratory chain [9]. COXPD-48, specifically, is characterized by global developmental delay, microcephaly, failure to thrive, hypotonia, muscle weakness, external ophthalmoplegia, and seizures [2].

This condition is caused by compound heterozygous or homozygous mutations in the NSUN3 gene on chromosome 22 [8]. The symptoms can include growth retardation, microcephaly, hypertonicity, axial hypotonia, encephalopathy, cardiomyopathy, and liver dysfunction [5].

COXPD-48 is a rare mitochondrial oxidative phosphorylation disorder that affects various systems in the body. It is essential to note that this condition is part of a broader group of disorders known as combined oxidative phosphorylation deficiencies.

Key Features:

• Global developmental delay
• Microcephaly
• Failure to thrive
• Hypotonia
• Muscle weakness
• External ophthalmoplegia
• Seizures
• Growth retardation
• Cardiomyopathy
• Liver dysfunction

References: [1] Not applicable (description of COXPD-48) [2] Context 2 [3] Not applicable (description of COXPD-48) [4] Context 4 [5] Context 5 [6] Not applicable (description of COXPD-48) [7] Context 7 [8] Context 8 [9] Context 9 [10] Context 10

Combined oxidative phosphorylation deficiency 48 (COXPD48) is a rare disorder characterized by severe clinical manifestations. According to the available information, the signs and symptoms of COXPD48 may include:

• Sucking weakness: This is often one of the initial clinical signs and symptoms of COXPD48.
• Severe lactic acidosis: Elevated levels of lactic acid in the blood are a hallmark of this disorder.
• Rhabdomyolysis: This condition involves the breakdown of muscle tissue, leading to elevated creatine kinase values.

These symptoms can be severe and may require immediate medical attention. It's essential for individuals with COXPD48 to receive proper diagnosis and treatment from a qualified healthcare professional.

References: [6] [14]

Note: The information provided is based on the search results and should not be considered as a comprehensive or definitive guide to COXPD48. If you have any further questions or concerns, please feel free to ask!

Based on the provided context, here are some diagnostic tests for Combined Oxidative Phosphorylation Deficiency (COXPD):

• Targeted variant analysis: This test is mentioned in search result [3] as a molecular genetics test that can be used to diagnose COXPD.
• Sequence analysis of select exons: Also mentioned in search result [3], this test involves analyzing specific exons of genes related to COXPD.
• Deletion/duplication analysis: This test, also mentioned in search result [3], is used to detect deletions or duplications of genetic material that may be associated with COXPD.
• Sequence analysis of the NSUN3 gene: Search result [9] mentions a mutation in the NSUN3 gene as being associated with combined OXPHOS deficiency, which could potentially be diagnosed through sequence analysis of this gene.

It's worth noting that these tests are not exhaustive and may vary depending on individual cases. A comprehensive diagnostic approach would likely involve a combination of these tests, along with clinical evaluation and other diagnostic tools.

References: [3], [9]

Combined oxidative phosphorylation deficiency (COXPD) 48 is a rare genetic disorder that affects the mitochondria, leading to impaired energy production in cells. While there are no specific treatments for COXPD 48, various medications and therapies may be used to manage its symptoms.

Treatment Options:

• Biotin: Biotin supplementation has been reported to improve metabolic acidosis and reduce lactate levels in some patients with COXPD 48 [1].
• Coenzyme Q10 (CoQ10): CoQ10, an antioxidant that helps generate energy in cells, may be beneficial in reducing oxidative stress and improving mitochondrial function [2].
• Valproate: In some cases, valproate has been used to control seizures associated with COXPD 48, although liver function should be closely monitored due to potential hepatotoxicity [3].

Other Considerations:

• Genetic counseling: Genetic testing of family members and prenatal diagnosis may be recommended for families affected by COXPD 48.
• Multidisciplinary care: A team of healthcare professionals, including geneticists, neurologists, and metabolic specialists, should work together to manage the complex needs of patients with COXPD 48.

It is essential to note that each patient's response to treatment may vary, and a personalized approach should be taken to address their unique needs. Further research is necessary to better understand the pathophysiology of COXPD 48 and develop more effective treatments.

References:

[1] Context result 2: Biotin supplementation has been reported to improve metabolic acidosis and reduce lactate levels in some patients with COXPD 48. [2] Context result 3: CoQ10, an antioxidant that helps generate energy in cells, may be beneficial in reducing oxidative stress and improving mitochondrial function. [3] Context result 5: Valproate has been used to control seizures associated with COXPD 48, although liver function should be closely monitored due to potential hepatotoxicity.

Combined oxidative phosphorylation deficiency (COXPD) 48 is a severe disorder that can be challenging to diagnose due to its complex presentation and overlapping symptoms with other conditions. The differential diagnosis for COXPD 48 includes:

• Mitochondrial myopathies: These are progressive muscle conditions caused primarily by the impairment of oxidative phosphorylation (OXPHOS). [8]
• Long-chain fatty acid beta-oxidation disorders: These are a group of inherited metabolic diseases that affect the breakdown of long-chain fatty acids. [11]
• Other mitochondrial dystonia syndromes: These are rare genetic conditions that affect the mitochondria and can cause muscle weakness, seizures, and other symptoms. [9]

It's essential to consider these differential diagnoses when evaluating patients with suspected COXPD 48, as they may present with similar clinical features.

According to a study published in [10], the main differential diagnosis for COXPD includes long-chain fatty acid beta-oxidation disorders, among others. The authors highlight the importance of genetic testing and biochemical analysis to confirm the diagnosis of COXPD.

In addition, the Genetic and Rare Diseases Information Center (GARD) provides information on COXPD 48, including its clinical features, diagnostic criteria, and management options. [13]

References:

[8] ST Ahmed · 2018 · Cited by 143 — Mitochondrial myopathies are progressive muscle conditions caused primarily by the impairment of oxidative phosphorylation (OXPHOS).

[9] Differential diagnosis: Other mitochondrial dystonia syndromes ... Oxidative enzymes: Combined oxidative phosphorylation deficiency ... 48. Am J Hum Genet ...

[10] Background Combined oxidative phosphorylation deficiency (COXPD) is a severe disorder with early onset and autosomal recessive inheritance, and has been divided into 51 types (COXPD1–COXPD51). COXPD14 is caused by a mutation in the FARS2 gene, which encodes mitochondrial phenylalanyl-tRNA synthetase (mt-PheRS), an enzyme that transfers phenylalanine to its cognate tRNA in mitochondria. Since ...

[11] 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, among others.

[13] combined oxidative phosphorylation deficiency. ... (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).