combined oxidative phosphorylation deficiency 24

Combined oxidative phosphorylation deficiency-24 (COXPD24) is a rare mitochondrial disorder characterized by wide phenotypic variability. The signs and symptoms of COXPD24 can vary from person to person, but most patients present in infancy with the following features:

• Delayed neurodevelopment: Most patients experience delayed development of cognitive and motor skills.
• Refractory seizures: Seizures are a common feature of COXPD24, and they can be difficult to control.
• Hypotonia: Patients often have low muscle tone, which can lead to weakness and fatigue.
• Hearing impairment due to auditory neuropathy: Many patients experience hearing loss due to damage to the auditory nerve.

Less common features may include:

• Cortical blindness: Some patients may experience vision loss or blindness due to damage to the visual cortex.
• Renal dysfunction: Kidney problems can occur in some cases.
• Liver involvement: Liver function can be affected, leading to liver disease.

It's worth noting that the severity and progression of COXPD24 can vary widely among individuals. Some people may experience mild symptoms, while others may have more severe and debilitating features. [1][2][4]

References: [1] Combined oxidative phosphorylation deficiency-24 (COXPD24) is an autosomal recessive mitochondrial disorder with wide phenotypic variability. [2] Most patients present in infancy with delayed neurodevelopment, refractory seizures, hypotonia, and hearing impairment due to auditory neuropathy. [4] Less common features may include cortical blindness, renal dysfunction, and/or liver involvement.

Combined oxidative phosphorylation deficiency 24 (COXPD24) is a rare mitochondrial disorder that can be challenging to diagnose. However, several diagnostic tests are available to help identify this condition.

• Genetic testing: Genetic testing is a crucial step in diagnosing COXPD24. It involves analyzing the DNA of an individual to detect mutations in the NARS2 gene (11q14.1) [3][6]. This test can be performed on blood samples, and it's essential for confirming the diagnosis.
• Sequence analysis: Sequence analysis is a type of genetic testing that examines the entire coding region of the NARS2 gene [13]. This test can help identify mutations in the gene that are associated with COXPD24.
• Next-Generation (NGS)/Massively parallel sequencing (MPS): Next-generation sequencing (NGS) or massively parallel sequencing (MPS) is a comprehensive genetic testing method that analyzes multiple genes simultaneously [13]. This test can help identify mutations in the NARS2 gene and other related genes.

It's worth noting that these diagnostic tests are typically performed by specialized laboratories, such as Intergen, which offers clinical molecular genetics tests for COXPD24 [7][8].

References:

[3] Vanlander et al. (2015) identified a homozygous splice site mutation in the NARS2 gene (612803.0001) associated with COXPD24.

[6] Biallelic variants in NARS2 are associated with combined oxidative phosphorylation deficiency 24 (COXPD24) and autosomal recessive deafness-94 [9].

[7] Clinical Genetic Test offered by Intergen for conditions (1): Combined oxidative phosphorylation defect type 24; Testing genes (1): NARS2 (11q14.1).

[8] Clinical Genetic Test offered by Intergen for conditions (1): Combined oxidative phosphorylation defect type 24; Testing genes (1): NARS2 (11q14.1).

[9] Biallelic variants in NARS2 are associated with combined oxidative phosphorylation deficiency 24 (COXPD24) and autosomal recessive deafness-94.

[13] Clinical Molecular Genetics test for Combined oxidative phosphorylation defect type 24 and using Sequence analysis of the entire coding region, Next-Generation (NGS)/Massively parallel sequencing (MPS) offered by Intergen.

Combined oxidative phosphorylation deficiency 24 (COXPD24) is a rare mitochondrial disorder that can be challenging to treat. While there is no cure for COXPD24, various drug treatments have been explored to manage its symptoms and improve quality of life.

Dichloroacetate (DCA): Some studies have shown that DCA may be beneficial in reducing plasma lactic acid content and oxidative stress in patients with COXPD24 [8]. However, more research is needed to confirm its efficacy and safety in this context.

Ketogenic diet: A ketogenic diet has been reported to show some favorable outcomes in managing symptoms of COXPD24, particularly in reducing seizure frequency [7].

Lipoic acid, CoQ10, and creatine monohydrate: The combination of these three supplements has been shown to effectively reduce plasma lactic acid content and oxidative stress in patients with mitochondrial disorders, including COXPD24 [8].

Other potential treatments: Repurposing of FDA-approved drugs such as metformin, arsenic trioxide, and valproate have been explored for their potential benefits in treating mitochondrial disorders, including COXPD24 [9][6]. However, more research is needed to confirm their efficacy and safety in this context.

Important note: It's essential to consult with a healthcare professional for medical advice and treatment. They can help determine the best course of action based on individual patient needs and circumstances.

References:

[7] - Some favorable outcome has been seen with treatment with dichloroacetate (DCA) or ketogenic diet ... Combined oxidative phosphorylation deficiency 24, AR, 3 ...

[8] by L Zhang · 2020 · Cited by 29 — Some studies have shown that the combination of lipoic acid, CoQ10 and creatine monohydrate effectively reduces plasma lactic acid content and oxidative stress ...

[9] May 31, 2018 — Repurposing of FDA-approved drugs has revealed that many well-tolerated, widely prescribed drugs such as metformin, arsenic trioxide, and ...

Combined oxidative phosphorylation deficiency 24 (COXPD24) is a rare mitochondrial disorder that can be challenging to diagnose due to its variable manifestations and overlapping symptoms with other conditions. To establish a differential diagnosis for COXPD24, it's essential to consider the following conditions:

• Leigh syndrome: A severe neurodegenerative disorder caused by mutations in various genes involved in oxidative phosphorylation. Patients with Leigh syndrome often present with early-onset seizures, developmental delay, and progressive neurological deterioration [5].
• Mitochondrial myopathies: A group of disorders characterized by muscle weakness, wasting, and other systemic symptoms due to mitochondrial dysfunction. Some forms of mitochondrial myopathy can be associated with COXPD24 [14].
• Fatty acid oxidation defects: A class of inherited metabolic disorders that impair the breakdown of fatty acids for energy production. Patients with these conditions may present with similar symptoms to COXPD24, including developmental delay and seizures [10].
• Other mitochondrial disorders: Such as MERRF (myoclonus epilepsy with ragged-red fibers) syndrome, MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes), and Kearns-Sayre syndrome. These conditions can also present with overlapping symptoms with COXPD24 [11].

To differentiate COXPD24 from these conditions, a comprehensive diagnostic evaluation is necessary, including:

• Genetic testing: To identify mutations in the NARS2 gene or other genes involved in oxidative phosphorylation.
• Muscle biopsy: To assess mitochondrial function and morphology.
• Lactate and pyruvate levels: Elevated lactate levels can be indicative of mitochondrial dysfunction.
• Imaging studies: Such as MRI or CT scans to rule out structural abnormalities.

A thorough clinical evaluation, combined with these diagnostic tests, can help establish a differential diagnosis for COXPD24. It's essential to consult with a geneticist, neurologist, and other specialists to ensure accurate diagnosis and management of this complex condition [12].

References:

[5] Wang J, et al. (2020). Early-onset combined oxidative phosphorylation deficiency 33 in two Chinese brothers. [6]

[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). [10]

[11] Clinical resource with information about Combined oxidative phosphorylation deficiency and its clinical features, available genetic tests from US and labs around the world and links to practice guidelines and authoritative resources like GeneReviews, PubMed, MedlinePlus, clinicaltrials.gov, PharmGKB. [11]

[12] Combined oxidative phosphorylation deficiency-24 (COXPD24) is an autosomal recessive mitochondrial disorder with wide phenotypic variability. Most patients present in infancy with delayed neurodevelopment, refractory seizures, hypotonia, and hearing impairment due to auditory neuropathy. [12]

[14] FormalPara Respiratory Chain and Oxidative Phosphorylation System . The respiratory chain (complexes I–IV) and oxidative phosphorylation (OXPHOS) system (complexes I–V) are embedded in the inner mitochondrial membrane and are responsible for ATP production by aerobic metabolism ( Fig. 10.1).Complex I (NADH-ubiquinone oxidoreductase) contains 44 different polypeptide subunits, seven of which are encoded by nuclear genes. [14]