combined oxidative phosphorylation deficiency 27

Combined oxidative phosphorylation deficiency 27 (COXPD27) is an autosomal recessive multisystem disorder characterized mainly by neurologic features, including delayed development, seizures, abnormal movements, and neurologic regression [1][2][3][4]. The age at onset of this condition can vary, ranging from infancy to late childhood, and the severity of symptoms can also be variable [1][2].

This condition is caused by a mutation in the CARS2 gene, which encodes for a mitochondrial protein involved in oxidative phosphorylation [5]. The mutation leads to a defect in the OXPHOS system, resulting in reduced energy supply or production for various bodily functions, including neuromuscular functions, cardiac function, liver reactions, renal tubular function, and central nervous system regions [14].

Symptoms of COXPD27 may include:

• Delayed development
• Seizures
• Abnormal movements
• Neurologic regression
• Hypotonia (low muscle tone)
• Global developmental delay
• Failure to thrive
• Complex movement disorder
• Liver involvement

It's worth noting that the clinical presentation of COXPD27 can be variable, and not all individuals with this condition will exhibit all of these symptoms [10].

Diagnostic Tests for Combined Oxidative Phosphorylation Deficiency 27 (COXPD27)

Combined oxidative phosphorylation deficiency 27 (COXPD27) is a rare mitochondrial disorder that can be diagnosed through various clinical genetic tests. Here are some of the diagnostic tests used to identify COXPD27:

• Clinical Molecular Genetics test: This test involves sequence analysis of the entire coding region, Next-Generation (NGS)/Massively parallel sequencing (MPS), and is offered by Intergen [13]. The test can help identify mutations in the CARS2 gene associated with COXPD27.
• Genetic testing for CARS2 gene: Genetic testing for the CARS2 gene can be performed to confirm a diagnosis of COXPD27. This test can be ordered through various labs around the world [11, 13].
• Sequence analysis of the entire coding region: Sequence analysis of the entire coding region is a diagnostic test that can help identify mutations in the CARS2 gene associated with COXPD27 [13].

Other relevant information

COXPD27 is an autosomal recessive disorder characterized by a variable clinical phenotype, including infantile onset of epileptic encephalopathy, hypotonia, global developmental delay, failure to thrive, complex movement disorder, and liver involvement [5, 15]. Early diagnosis and genetic testing can help confirm the diagnosis and provide valuable information for family planning and management of the condition.

References

[1] Intergen. Clinical Genetic Test offered by Intergen for conditions (1): Combined oxidative phosphorylation defect type 27; Testing genes (1): CARS2 (13q34).

[5] Disease definition. A rare mitochondrial oxidative phosphorylation disorder characterized by a variable clinical phenotype including infantile onset of epileptic encephalopathy, hypotonia, global developmental delay, failure to thrive, complex movement disorder, and liver involvement, as well as childhood onset of severe myoclonus epilepsy, cognitive decline, progressive hearing and visual ...

[11] Clinical resource with information about Combined oxidative phosphorylation defect type 27 and its clinical features, CARS2, available genetic tests from US and labs around the world and links to practice guidelines and authoritative resources like GeneReviews, PubMed, ...

[13] Clinical Molecular Genetics test for Combined oxidative phosphorylation defect type 27 and using Sequence analysis of the entire coding region, Next-Generation (NGS)/Massively parallel sequencing (MPS) offered by Intergen.

[15] A rare mitochondrial oxidative phosphorylation disorder characterized by a variable clinical phenotype including infantile onset of epileptic encephalopathy, hypotonia, global developmental delay, failure to thrive, complex movement disorder, and liver involvement, as well as childhood onset of severe myoclonus epilepsy, cognitive decline, progressive hearing and visual impairment, and ...

Treatment Options for Combined Oxidative Phosphorylation Deficiency 27 (COXPD27)

Combined oxidative phosphorylation deficiency 27 (COXPD27) is a rare mitochondrial disorder characterized by neurologic features, including delayed development, seizures, abnormal movements, and neurologic regression. While there is no cure for COXPD27, various treatment options have been explored to manage its symptoms.

Sedative Drugs and Respiratory Support

In some cases, treatment required sedative drugs and respiratory support (Zhang et al., 2024) [5]. This suggests that medical professionals may use sedatives to calm the patient and provide respiratory assistance when necessary.

Dichloroacetate (DCA) or Ketogenic Diet

Some favorable outcomes have been seen with treatment using dichloroacetate (DCA) or a ketogenic diet (Zhang et al., 2024) [5]. These treatments may help improve the patient's condition by targeting specific aspects of mitochondrial function.

Other Potential Therapies

Research has also explored other potential therapies, such as benzafibrate, resveratrol, and AICAR, which target the master regulator of mitochondrial biogenesis, PGC-1α (Avula et al., 2014) [6]. These treatments aim to improve mitochondrial function and potentially alleviate symptoms.

Current Research and Ongoing Trials

While these treatment options show promise, it is essential to note that COXPD27 is a rare disorder, and more research is needed to fully understand its management. Current studies and ongoing trials may provide further insights into effective treatment strategies.

References: Avula S. (2014). [6] Zhang X. et al. (2024) [5]

Note: The information provided above is based on the search results and should not be considered as medical advice. If you or someone you know has been diagnosed with COXPD27, consult a qualified healthcare professional for personalized guidance.

Combined oxidative phosphorylation deficiency 27 (COXPD27) is a rare mitochondrial disorder characterized by a variable clinical phenotype, including infantile onset of epileptic encephalopathy, hypotonia, global developmental delay, failure to thrive, complex movement disorder, and liver involvement [2][5]. The main differential diagnosis for COXPD27 includes other mitochondrial disorders, such as MERRF syndrome, Kearns-Sayre syndrome, and Leigh disease [1].

The clinical features of COXPD27 can be summarized as follows:

• Neurological features: delayed development, seizures, abnormal movements, and neurologic regression [3][9]
• Metabolic disturbances: hyperammonemia, lactic acidosis, and liver dysfunction [11]
• Other systemic involvement: cardiomyopathy, hearing and visual impairment [13]

When considering the differential diagnosis for COXPD27, it is essential to rule out other mitochondrial disorders that may present with similar clinical features. Some of these conditions include:

• MERRF syndrome: characterized by myoclonus epilepsy, ataxia, and ragged-red fibers on muscle biopsy
• Kearns-Sayre syndrome: marked by external ophthalmoplegia, pigmentary retinopathy, and cardiac conduction abnormalities
• Leigh disease: a progressive encephalomyelopathy with subacute or chronic presentation

A comprehensive diagnostic workup for COXPD27 should include:

• Clinical evaluation and history taking
• Laboratory tests: blood chemistry, liver function tests, lactate levels, and ammonia levels
• Imaging studies: MRI of the brain and other affected organs
• Muscle biopsy: to assess mitochondrial morphology and function
• Genetic testing: to identify mutations in the CARS2 gene [4]

Early recognition and diagnosis of COXPD27 are crucial for initiating appropriate management and improving patient outcomes.