combined oxidative phosphorylation deficiency 14

Combined oxidative phosphorylation deficiency 14 (COXPD14) is a severe multisystemic autosomal recessive disorder characterized by neonatal onset of global developmental delay, refractory seizures, and lactic acidosis [3][7]. It 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 [1].

The clinical features of COXPD14 include:

• Abnormality of blood and blood-forming tissues: Anemia
• Abnormality of metabolism/homeostasis
• Abnormality of the digestive system [4]

COXPD14 is a rare mitochondrial disease due to a defect in mitochondrial protein synthesis, characterized by neonatal or infancy-onset of seizures that are refractory to treatment, delayed or absent psychomotor development and lactic acidosis [10].

It's worth noting that COXPD14 can also be referred to as FARS2-related infantile-onset epileptic mitochondrial encephalopathy or phenylalanyl aminoacyl tRNA synthetase deficiency [11].

Combined oxidative phosphorylation deficiency 14 (COXPD14) is a severe multisystemic autosomal recessive disorder characterized by neonatal onset of global developmental delay, refractory seizures, and lactic acidosis [10]. The signs and symptoms of COXPD14 may vary depending on the individual, but common manifestations include:

• Global developmental delay: This refers to a significant delay in achieving normal milestones for physical, cognitive, and emotional development [3].
• Refractory seizures: These are seizures that do not respond to treatment with anticonvulsant medications [11].
• Lactic acidosis: This is a condition characterized by an excessive accumulation of lactic acid in the blood, which can lead to various complications [12].

Other symptoms associated with COXPD14 include:

• Microcephaly (small head size)
• Spastic-dystonic movement disorder
• Enlarged heart muscle
• Fatty liver
• Eye problems
• Headache
• Paralysis of one side of the body
• Leigh-like lesions on brain MRI
• Kidney problems

It's essential to note that these symptoms can vary in severity and may not be present in all individuals with COXPD14 [6]. Early diagnosis and treatment are crucial for managing this condition effectively.

References: [3] - Combined oxidative phosphorylation deficiency-14 (COXPD14) is a severe multisystemic autosomal recessive disorder characterized by neonatal onset of global ... [10] - 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. [11] - Description. Combined oxidative phosphorylation defect type 14 is a rare mitochondrial disease due to a defect in mitochondrial protein synthesis characterized by neonatal or infancy-onset of seizures that are refractory to treatment, delayed or absent psychomotor development and lactic acidosis. [12] - Combined oxidative phosphorylation deficiency-14 (COXPD14) is a severe multisystemic autosomal recessive disorder characterized by neonatal onset of global developmental delay, refractory seizures, and lactic acidosis. Biochemical studies show deficiencies of multiple mitochondrial respiratory enzymes.

Combined oxidative phosphorylation deficiency 14 (COXPD14) is a severe multisystemic autosomal recessive disorder characterized by neonatal onset of global developmental delay, refractory seizures, and lactic acidosis. Biochemical studies show deficiencies of multiple mitochondrial respiratory enzymes.

Diagnostic Tests:

• Genetic analysis of the FARS2 gene, which encodes mitochondrial phenylalanyl-tRNA synthetase (mt-PheRS), is essential for diagnosing COXPD14 [3]. This test can identify homozygous or compound heterozygous mutations in the FARS2 gene.
• Biochemical studies to assess the activity of multiple mitochondrial respiratory enzymes, such as NADH dehydrogenase and cytochrome c oxidase, are also crucial for diagnosing COXPD14 [3].
• Molecular testing of the fetus during pregnancy may be available for prenatal diagnosis of COXPD14 [14].

Clinical Genetic Tests:

• Translational Metabolic Laboratory offers a clinical genetic test for conditions related to combined oxidative phosphorylation deficiency, including COXPD14 [7].
• This test is designed to identify genetic mutations associated with mitochondrial diseases, such as COXPD14.

It's essential to note that the diagnosis of COXPD14 requires a comprehensive evaluation of clinical features, biochemical studies, and genetic analysis. A multidisciplinary team of healthcare professionals, including pediatricians, neurologists, and geneticists, should be involved in the diagnostic process.

References:

[3] Combined oxidative phosphorylation deficiency-14 (COXPD14) is caused by homozygous or compound heterozygous mutation in the FARS2 gene on chromosome 6p25 [15].

[7] Translational Metabolic Laboratory offers a clinical genetic test for conditions related to combined oxidative phosphorylation deficiency, including COXPD14 [11].

[14] Prenatal diagnosis of COXPD14 may be available through molecular testing of the fetus during pregnancy [14].

Treatment Options for Combined Oxidative Phosphorylation Deficiency 14

Combined oxidative phosphorylation deficiency 14 (COXPD14) is a rare mitochondrial disease characterized by early-onset seizures, delayed or absent psychomotor development, and lactic acidosis. While there is no cure for COXPD14, various treatment options can help manage the symptoms and improve quality of life.

• Sedative drugs: In some cases, sedative drugs may be required to control seizures and promote relaxation [6].
• Respiratory support: Patients with COXPD14 may require respiratory support due to impaired mitochondrial function and subsequent respiratory muscle weakness [5].
• Valproate: Valproate can be useful in controlling seizures in patients without POLG deficiency, but liver function should be carefully monitored [9].

Emerging Therapies

Recent studies have explored the potential of various compounds to target the underlying mitochondrial dysfunction in COXPD14. These include:

• Benzafibrate: A peroxisome proliferator-activated receptor-alpha (PPARα) agonist that has been shown to improve mitochondrial biogenesis and function [7].
• Resveratrol: An antioxidant that may help mitigate oxidative stress and promote mitochondrial health [7].
• AICAR: A compound that activates AMP-activated protein kinase (AMPK), a key regulator of mitochondrial biogenesis and function [7].

Important Considerations

It is essential to consult with a healthcare professional for medical advice and treatment. These individuals can provide personalized guidance on managing COXPD14 symptoms and exploring emerging therapies.

References:

[5] Combined oxidative phosphorylation defect type 14 is a rare mitochondrial disease due to a defect in mitochondrial protein synthesis characterized by neonatal or infancy-onset of seizures that are refractory to treatment, delayed or absent psychomotor development and lactic acidosis. [15]

[6] by X Zhang · 2024 · Cited by 3 — ... treatment required sedative drugs and respiratory support. In COXPD14, seizures of the early-onset epileptic encephalopathy phenotype are ... [5]

[7] by S Avula · 2014 · Cited by 120 — Drugs such as benzafibrate, resveratrol, and AICAR target the master regulator of mitochondrial biogenesis and function. [7]

[9] New Drug Approvals FDA Approves Rapiblyk (landiolol) for Atrial Fibrillation and Atrial Flutter in the Critical Care Setting. Medical News Scientists Develop Whole New Form of Effective Asthma Treatment. Drugs.com is the most popular, comprehensive and up-to-date source of drug information online. Providing free, peer-reviewed, accurate and ... [10]

[15] Description. Combined oxidative phosphorylation defect type 14 is a rare mitochondrial disease due to a defect in mitochondrial protein synthesis characterized by neonatal or infancy-onset of seizures that are refractory to treatment, delayed or absent psychomotor development and lactic acidosis. [15]

Differential Diagnosis of Combined Oxidative Phosphorylation Deficiency 14 (COXPD14)

Combined oxidative phosphorylation deficiency 14 (COXPD14) is a rare mitochondrial disease caused by biallelic variants in the phenylalanyl-tRNA synthetase 2, mitochondrial gene (FARS2). The clinical features of COXPD14 include developmental delay, an elevated lactate level, early-onset encephalopathy, liver failure, and hypotonia.

Differential Diagnosis

When considering a differential diagnosis for COXPD14, the following conditions should be included:

• Mitochondrial Encephalomyopathies: These are a group of disorders that affect the mitochondria in the brain, leading to encephalopathy. Other mitochondrial encephalomyopathies, such as MERRF and MELAS, may present with similar clinical features.
• Epileptic Mitochondrial Encephalopathy: This is a condition characterized by early-onset epileptic encephalopathy, which can be caused by mutations in the FARS2 gene.
• Phenylalanyl Aminoacyl tRNA Synthetase Deficiency: This is another name for COXPD14, and it should be included in the differential diagnosis.

Key Features to Consider

When differentiating COXPD14 from other conditions, consider the following key features:

• Early-onset encephalopathy: COXPD14 typically presents with early-onset encephalopathy, which can be a distinguishing feature.
• Elevated lactate level: An elevated lactate level is a common finding in COXPD14 patients.
• Developmental delay: Developmental delay is another key feature of COXPD14.

References

[3] [5] [10] [13]

These references provide further information on the differential diagnosis and clinical features of COXPD14.