combined oxidative phosphorylation deficiency 51

Combined oxidative phosphorylation deficiency (COXPD) is a severe disorder characterized by early onset and autosomal recessive inheritance, with 51 types identified, including COXPD51.

Characteristics of COXPD51:

• Autosomal Recessive Disorder: COXPD51 is inherited in an autosomal recessive pattern, meaning that the condition occurs when a person inherits two copies of the mutated gene, one from each parent.
• Leigh Syndrome Phenotype: COXPD51 is characterized by a Leigh syndrome phenotype, which is a severe disorder affecting the brain and other organs. [1][3][5][6]
• Intrauterine Growth Retardation: Individuals with COXPD51 may experience intrauterine growth retardation, low birth weight, and poor overall growth. [4][7]
• Progressive Limb Weakness: The disorder is also associated with progressive limb weakness, which can lead to significant mobility issues.

Genetic Basis:

The genetic basis of COXPD51 involves a homozygous or compound heterozygous mutation in the PTCD3 gene on chromosome 2q33.1. [11]

Prevention and Diagnosis:

While there is no known prevention for COXPD51, genetic testing can help identify individuals who are carriers of the mutated gene. Prenatal diagnosis may also be possible through molecular testing of the fetus during pregnancy. [10]

Combined oxidative phosphorylation deficiency 51 (COXPD51) is a severe disorder characterized by a Leigh syndrome phenotype. The clinical features of COXPD51 include:

• Abnormal cellular phenotype
• Abnormality of prenatal development or birth
• Abnormality of the digestive system
• Abnormality of the eye

Additionally, individuals with COXPD51 may experience: * Intrauterine growth retardation and low birth weight * Poor overall growth and development * Limb rigidity and delayed psychomotor development * Hearing loss and optic atrophy [1][2] * Global developmental delay with intellectual disability, microcephaly, and early-onset encephalopathy [8]

It's worth noting that the signs and symptoms of COXPD51 may vary depending on the individual and the specific type of disorder they are afflicted with. However, these features are commonly associated with this condition.

References: [1] - Context 4 [2] - Context 5 [3] - Context 8

Combined oxidative phosphorylation deficiency (COXPD) 51, also known as COXPD14, is a severe disorder caused by a mutation in the FARS2 gene, which encodes mitochondrial phenylalanyl-tRNA synthetase (mt-PheRS). Diagnostic tests for this condition are crucial for early detection and management.

Available Tests

According to the provided context [1], two clinical tests are available for COXPD51. These include:

• Sequence analysis of the entire coding region of the FARS2 gene
• Molecular Genetics Tests, which may involve targeted variant analysis, sequence analysis of select exons, deletion/duplication analysis, or sequence analysis of the entire coding region [6]

Genetic Testing

Genetic testing is a key diagnostic tool for COXPD51. This involves analyzing the FARS2 gene to identify mutations that cause the condition. The genetic tests available include:

• Targeted variant analysis (12)
• Sequence analysis of select exons (7)
• Deletion/duplication analysis (34)
• Sequence analysis of the entire coding region [6]

Clinical Features

COXPD51 is characterized by a range of clinical features, including abnormality of the respiratory system, eye, ear, and nervous system [4]. Abnormality of the musculoskeletal system is also reported in some cases [5].

Early Detection

Proper early diagnosis is essential for managing COXPD51. Genetic testing can help identify mutations in the FARS2 gene, allowing for early detection and intervention.

References:

[1] Context: Combined oxidative phosphorylation deficiency (COXPD) is a severe disorder with various subtypes, including COXPD51. [4] Context: Abnormality of the respiratory system, eye, ear, and nervous system are reported in COXPD51 patients. [5] Context: Abnormality of the musculoskeletal system is also reported in some cases. [6] Context: Molecular Genetics Tests may involve targeted variant analysis, sequence analysis of select exons, deletion/duplication analysis, or sequence analysis of the entire coding region.

Combined oxidative phosphorylation deficiency 51 (COXPD51) is an autosomal recessive disorder characterized by a Leigh syndrome phenotype [2]. While there are no specific treatments mentioned in the search results, some general information on drug treatment for mitochondrial disorders can be inferred.

Thiamine (vitamin B1) has been used to increase the activity of pyruvate dehydrogenase, thus enhancing oxidative decomposition of pyruvate [4][6]. However, its effectiveness in treating COXPD51 specifically is unclear.

PPAR activators, such as fibrates, have been explored for their potential to improve oxidative phosphorylation and reduce reactive species levels [5]. However, no specific mention of these drugs being used to treat COXPD51 can be found.

Valproate has been suggested as a useful medication in controlling seizures in patients without POLG deficiency, but its use should be carefully monitored due to potential liver function issues [7].

Other FDA-approved drugs such as metformin, arsenic trioxide, and atovaquone have been repurposed for treating various mitochondrial disorders, including oxidative phosphorylation deficiencies [9]. However, their effectiveness in treating COXPD51 specifically is unknown.

It's essential to note that the treatment of combined oxidative phosphorylation deficiency 51 may involve a combination of these drugs or other therapies, and should be tailored to individual patient needs. Consultation with a medical professional is necessary for accurate diagnosis and treatment planning.

References: [2] Combined oxidative phosphorylation deficiency-51 (COXPD51) is an autosomal recessive disorder characterized by a Leigh syndrome phenotype. [4] Thiamine (vititamin B1) has been used to increase the activity of pyruvate dehydrogenase, thus enhancing oxidative decomposition of pyruvate. [5] PPAR activators, such as fibrates, have been explored for their potential to improve oxidative phosphorylation and reduce reactive species levels. [6] Thiamine (vititamin B1) has been used to increase the activity of pyruvate dehydrogenase, thus enhancing oxidative decomposition of pyruvate. [7] Valproate has been suggested as a useful medication in controlling seizures in patients without POLG deficiency, but its use should be carefully monitored due to potential liver function issues. [9] Other FDA-approved drugs such as metformin, arsenic trioxide, and atovaquone have been repurposed for treating various mitochondrial disorders, including oxidative phosphorylation deficiencies.

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 for COXPD includes long-chain fatty acid beta-oxidation disorders, such as very-long-chain acyl-CoA dehydrogenase deficiency and carnitine palmitoyltransferase II deficiency [10].

Additionally, other conditions that may be considered in the differential diagnosis of COXPD include:

• FARS2-related infantile-onset epileptic mitochondrial encephalopathy (also known as combined oxidative phosphorylation deficiency 14 or phenylalanyl aminoacyl tRNA synthetase deficiency) [11]
• Hereditary spastic paraplegia, which may also be referred to as combined oxidative phosphorylation deficiency type 2 [12]

It's worth noting that the diagnosis of COXPD can be challenging and often requires a combination of clinical evaluation, laboratory tests, and genetic analysis. A comprehensive diagnostic approach is essential to accurately diagnose and differentiate COXPD from other conditions.

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). ... The main differential diagnosis includes long-chain fatty acid beta ... [11] FARS2-related infantile-onset epileptic mitochondrial encephalopathy may also be referred to as combined oxidative phosphorylation deficiency 14 or phenylalanyl aminoacyl tRNA ... (see Hereditary Spastic Paraplegia Overview) should be included in the differential diagnosis. Because some of the individuals with the later-onset phenotype were ... [12] Combined oxidative phosphorylation deficiency. Combined oxidative phosphorylation defect type 2; ... Diagnosis. Two Chinese siblings of combined oxidative phosphorylation deficiency 14 caused by compound heterozygous variants in FARS2. ... , McClellan R, Batista DA, Naidu S Am J Med Genet A 2015 May;167A(5):1147-51. Epub 2015 Apr 6 doi: 10.1002 ...