combined oxidative phosphorylation deficiency 26

Combined oxidative phosphorylation deficiency 26 (COXPD26) is a rare mitochondrial disorder characterized by a highly variable phenotype, which may present as exercise intolerance with episodes of metabolic decompensation beginning in infancy that can result in mild muscle weakness [1]. The condition is caused by mutations in the TRMT5 gene, which plays a crucial role in the assembly and modification of mitochondrial proteins [3].

The symptoms of COXPD26 can vary widely among affected individuals, but may include episodes of metabolic decompensation, muscle weakness, and other systemic complications [4]. In some cases, the condition may present with severe brain dysfunction (encephalopathy) that worsens over time, along with difficulty growing and gaining weight at the expected rate [12].

COXPD26 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 [2]. Genetic testing can confirm the diagnosis and identify the specific mutation responsible for the condition.

It's worth noting that COXPD26 is one of several combined oxidative phosphorylation deficiencies, which are a group of multisystem inherited metabolic diseases due to genetically determined defects involving primarily the mitochondrial oxidative phosphorylation system (OXPHOS) [14].

Combined Oxidative Phosphorylation Deficiency (COXPD) 26, also known as COXPD28, is a rare mitochondrial disorder caused by mutations in the SLC25A26 gene. The signs and symptoms of this condition can vary, but they often include:

• Global developmental delay: Children with COXPD26 may experience significant delays in their physical, cognitive, and emotional development.
• Microcephaly: Some individuals with COXPD26 may have a smaller-than-average head size (microcephaly).
• Seizures: Seizures are a common symptom of COXPD26, and can range from mild to severe.
• Muscle weakness: Muscle weakness or hypotonia is another characteristic feature of COXPD26.
• Ragged red fibers: A skeletal muscle biopsy may reveal ragged red fibers, which are indicative of mitochondrial dysfunction.

According to the literature [8], individuals with COXPD28 (also known as COXPD26) often experience a range of symptoms, including:

• Enlarged heart muscle: Some people with COXPD26 may have an enlarged heart muscle.
• Fatty liver: Fatty liver is another potential symptom of this condition.
• Eye problems: Eye problems, such as vision impairment or blindness, can occur in some individuals with COXPD26.
• Headache: Headaches are a common complaint among people with COXPD26.
• Paralysis: In severe cases, paralysis of one side of the body (hemiplegia) may occur.

It's essential to note that the severity and progression of symptoms can vary significantly from person to person [11]. The prognosis for individuals with COXPD26 depends on the severity of their symptoms and associated complications.

Combined Oxidative Phosphorylation Deficiency 26 (COXPD26) is a rare mitochondrial disorder caused by mutations in the SLC25A26 gene. While there are no specific treatments for COXPD26, various medications and therapies may be used to manage its symptoms.

Treatment Overview

The treatment of COXPD26 typically involves a multidisciplinary approach, including medical management, nutritional support, and physical therapy. The primary goal is to alleviate the symptoms and improve the quality of life for affected individuals.

• Medical Management: This may include medications to manage symptoms such as muscle weakness, fatigue, and seizures. However, there are no specific drugs that target the underlying mitochondrial dysfunction in COXPD26.
• Nutritional Support: A balanced diet rich in vitamins, minerals, and antioxidants is essential for individuals with COXPD26. In some cases, nutritional supplements may be recommended to address specific deficiencies.
• Physical Therapy: Regular physical therapy can help maintain muscle strength and mobility, as well as improve overall functional ability.

Specific Medications

While there are no specific drugs that target the underlying mitochondrial dysfunction in COXPD26, various medications may be used to manage its symptoms. These include:

• Anticonvulsants: To control seizures and other neurological symptoms.
• Muscle relaxants: To alleviate muscle weakness and spasticity.
• Pain management medications: To address pain associated with muscle weakness or other symptoms.

References

1. [5] An important gene associated with Combined Oxidative Phosphorylation Deficiency 28 is SLC25A26 (Solute Carrier Family 25 Member 26). Affiliated tissues include skeletal muscle and heart, and related phenotypes are increased serum pyruvate and generalized hypotonia.
2. [13] 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 ...

Combined oxidative phosphorylation deficiency (COXPD) 26, also known as TRMT5-related mitochondrial disease, is a rare and severe disorder that affects the mitochondria's ability to produce energy for the body. When it comes to differential diagnosis, several conditions should be considered.

• Long-chain fatty acid beta-oxidation disorders: These are a group of metabolic disorders caused by defects in the breakdown of long-chain fatty acids. They can present with similar symptoms to COXPD 26, such as developmental delay, seizures, and liver dysfunction [10].
• Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS): This is a rare mitochondrial disorder that affects the brain, leading to symptoms like seizures, muscle weakness, and vision loss. While it's not directly related to COXPD 26, MELAS can be considered in the differential diagnosis due to overlapping clinical features [12].
• Hereditary spastic paraplegia (HSP): This is a group of genetic disorders that affect the nervous system, leading to progressive weakness and stiffness in the legs. Some forms of HSP can present with similar symptoms to COXPD 26, such as developmental delay and seizures [13].

It's essential to note that differential diagnosis for COXPD 26 involves a comprehensive evaluation of clinical features, laboratory tests, and genetic analysis. A precise diagnosis can be made by identifying the specific genetic mutation responsible for the condition.

References:

[10] Combined oxidative phosphorylation deficiency (COXPD) is a severe disorder belonging to mitochondrial diseases with an autosomal recessive inheritance pattern... [10] [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). ... The main differential diagnosis includes long-chain fatty acid beta-oxidation disorders... [12] [13] FARS2-related infantile-onset epileptic mitochondrial encephalopathy may also be referred to as combined oxidative phosphorylation deficiency 14 or phenylalanyl aminoacyl tRNA synthetase ... (see Hereditary Spastic Paraplegia Overview) should be included in the differential diagnosis. [13]