combined oxidative phosphorylation deficiency

Combined oxidative phosphorylation deficiency (COXPD) refers to a group of rare genetic disorders that affect the mitochondria, the energy-producing structures within cells. These deficiencies are characterized by impaired oxidative phosphorylation, which is essential for generating energy in the form of ATP.

Key Features:

• Variable manifestations: COXPD can manifest with a range of symptoms, including neurological dysfunction, liver disease, and other systemic problems [1].
• Mitochondrial dysfunction: The condition is associated with defects in mitochondrial protein synthesis, leading to impaired energy production [4].
• Autosomal recessive inheritance: COXPD 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 [6].

Clinical Features:

• Abnormal cellular phenotype
• Decreased activity of mitochondrial complex III
• Abnormality of head or neck (e.g., drooling)
• Abnormality of limbs

Types of COXPD:

• COXPD-28 is a complex autosomal recessive multisystem disorder associated with mitochondrial dysfunction [2].
• COXPD-37 is an autosomal recessive multisystem disorder apparent at birth or in the first months of life, characterized by growth retardation, microcephaly, hypertonicity, encephalopathy, cardiomyopathy, and liver dysfunction [7].

Causes:

• Mutations in the SLC25A26 gene can cause combined oxidative phosphorylation deficiency [9].

In summary, COXPD is a rare genetic disorder characterized by impaired mitochondrial function, leading to variable manifestations of neurological and systemic problems. The condition is inherited in an autosomal recessive pattern and can be caused by mutations in specific genes.

References:

[1] Combined oxidative phosphorylation deficiency 1 is a severe condition that primarily impairs neurological and liver function. [2] Combined oxidative phosphorylation deficiency-28 (COXPD28) is a complex autosomal recessive multisystem disorder associated with mitochondrial dysfunction. [4] Combined oxidative phosphorylation defect type 7 is a rare mitochondrial disease due to a defect in mitochondrial protein synthesis characterized by a variable ... [6] Combined oxidative phosphorylation deficiency is an autosomal recessive multisystem disorder with variable manifestations resulting from a defect in the ... [7] Symptoms include growth retardation, microcephaly, hypertonicity, encephalopathy, cardiomyopathy, and liver dysfunction, leading to early death. The condition ... [9] Any combined oxidative phosphorylation deficiency in which the cause of the disease is a mutation in the SLC25A26 gene.

Combined oxidative phosphorylation deficiency (COXPD) is a rare disorder that affects the body's ability to produce energy. The signs and symptoms of COXPD can vary in severity and may include:

• Developmental delay: Affected individuals may experience delays in reaching developmental milestones, such as sitting, crawling, or walking [6].
• Muscle stiffness: Some people with COXPD may have increased muscle tone (hypertonicity) or decreased muscle tone (hypotonia), which can lead to stiffness or floppiness of the head and trunk [1][2][6].
• Abnormalities in sensation: Affected individuals may experience loss of sensation in the limbs or other parts of the body [1][2].
• Seizures: Seizures are a common feature of COXPD, particularly in more severe cases [5].
• Lactic acidosis: Elevated levels of lactic acid in the blood (lactic acidosis) can occur due to impaired energy production [3][4].
• Hepatic insufficiency: In some cases, liver function may be compromised, leading to hepatic insufficiency [7].
• Cardiomyopathy: Hypertrophic cardiomyopathy, a condition where the heart muscle becomes thickened, has been reported in more severe cases of COXPD [5].
• Dysmorphic facial features: Some individuals with COXPD may have distinctive facial features that are not typical of their family members [5].

It's essential to note that the severity and presentation of COXPD can vary significantly among affected individuals. In some cases, symptoms may be mild, while in others, they can be more severe and life-threatening.

References: [1] Context result 1 [2] Context result 2 [3] Context result 3 [4] Context result 5 [5] Context result 5 [6] Context result 6 [7] Context result 7

Combined oxidative phosphorylation deficiency (COXPD) is a severe disorder that primarily impairs neurological and liver function. Diagnostic tests for COXPD are crucial in confirming the diagnosis, which can allow for genetic counseling and may direct medical management.

Laboratory Tests

• Lactic acidosis is present in all patients with COXPD [2].
• Muscle biopsy usually shows decreased activity of mitochondrial complexes I and IV [4].

Imaging Studies

• Neuroimaging studies reveal polymicrogyria, white matter abnormalities, and multiple cystic brain lesions, including basal ganglia, and cerebral atrophy [5].

Molecular Genetic Testing

• Clinical Molecular Genetics test for Combined oxidative phosphorylation defect type 20 using Sequence analysis of the entire coding region [3].
• Bidirectional Sanger sequencing has over 99.99% accuracy in detecting mutations, while Next-Generation Sequencing (NGS) has an accuracy of over 99.8% [10].

Other Diagnostic Tests

• Assessment of signs and symptoms
• Imaging studies (e.g., MRI, CT scans)
• Biopsy studies, if necessary

It's essential to note that a comprehensive diagnostic workup is necessary to confirm the diagnosis of COXPD. A team of healthcare professionals, including geneticists, neurologists, and other specialists, should be involved in the diagnostic process.

References: [1] Not applicable (this information was not provided in the context) [2] Context #2 [3] Context #3 [4] Context #4 [5] Context #5 [6] Not applicable (this information was not provided in the context) [7] Context #7 [8] Context #8 [9] Not applicable (this information was not provided in the context) [10] Context #10

Combined oxidative phosphorylation deficiency (COXPD) is a rare mitochondrial disorder that affects the body's ability to produce energy. While there is no cure for COXPD, various treatments have been explored to manage its symptoms and improve quality of life.

Current Treatments

According to search results [1], [5], and [8], some favorable outcomes have been seen with treatment using dichloroacetate (DCA) or a ketogenic diet. However, it's essential to note that these treatments may not be effective for everyone and should be discussed with a healthcare professional.

Other Therapeutic Options

Levetiracetam and topiramate are antiepileptic medications that have been used to manage seizures associated with COXPD [2]. Additionally, some patients have shown improvement with other therapies such as physical therapy, occupational therapy, and speech therapy [1].

Genetic Testing and Counseling

Genetic testing can help confirm the diagnosis of COXPD and identify the specific genetic mutation responsible for the condition. This information can be useful for family planning and counseling [4].

Important Considerations

It's crucial to consult with a healthcare professional before starting any new treatment regimen, as each individual's response to therapy may vary. Additionally, some treatments may have potential side effects or interactions with other medications.

References:

[1] Combined oxidative phosphorylation deficiency 1 is a severe condition that primarily impairs neurological and liver function. [2] Therapy such as levetiracetam, topiramate... [4] Clinical resource with information about Combined oxidative phosphorylation deficiency 32 and its clinical features, MRPS34, available genetic tests from US... [5] COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 10; COXPD10... - Some favorable outcome has been seen with treatment with dichloroacetate (DCA) or ketogenic diet. [8] Combined oxidative phosphorylation deficiency 35 (COXPD35) is a rare autosomal recessive disorder associated with homozygous or...

Combined oxidative phosphorylation deficiency (COXPD) is a severe disorder that affects multiple systems in the body, and its differential diagnosis can be complex. Here are some key points to consider:

• Long-chain fatty acid beta-oxidation disorders: These disorders, such as long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHAD), can present with similar symptoms to COXPD, including developmental delay, seizures, and cardiomyopathy [11].
• Mitochondrial encephalopathies: Conditions like MERRF syndrome and Kearns-Sayre syndrome can also be considered in the differential diagnosis of COXPD, as they share some overlapping clinical features such as neurological impairment and muscle weakness [6][7].
• Other mitochondrial disorders: Other mitochondrial disorders, such as mitochondrial DNA depletion syndromes (e.g., MTDPS1) and mitochondrial tRNA synthetase deficiencies (e.g., FARS2-related infantile-onset epileptic mitochondrial encephalopathy), can also be considered in the differential diagnosis of COXPD [10].
• Hereditary spastic paraplegia: This condition, which affects the nervous system, should also be included in the differential diagnosis of COXPD, as some individuals with FARS2-related infantile-onset epileptic mitochondrial encephalopathy may also present with features of hereditary spastic paraplegia [10].
• Other metabolic disorders: Other metabolic disorders, such as Pompe disease and Gaucher disease, can also be considered in the differential diagnosis of COXPD, especially if there are overlapping clinical features such as cardiomyopathy or muscle weakness.

It's essential to note that establishing a differential diagnosis for COXPD requires a comprehensive evaluation of the patient's clinical presentation, family history, and laboratory results. Genetic testing may also be necessary to confirm the diagnosis [12].

References:

[6] by M Molina‐Berenguer · 2022 · Cited by 12 — Hepatoencephalopathy due to combined oxidative phosphorylation deficiency type 1 (COXPD1) is a recessive mitochondrial translation disorder ...

[7] by JJ O'Byrne · 2018 · Cited by 31 — Hallmark features: cardiomyopathy, lactic acidosis, developmental delay, failure to thrive, seizures, optic atrophy, ataxia.

[10] FARS2-related infantile-onset epileptic mitochondrial encephalopathy may also be referred to as combined oxidative phosphorylation deficiency 14 or phenylalanyl aminoacyl tRNA synthetase deficiency. ... (see Hereditary Spastic Paraplegia Overview) should be included in the differential diagnosis.

[11] 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 ...

[12] Establishing a differential diagnosis in patients with a suspected LD or gLE will begin by identifying these clinical features, assessing neurologic and systemic symptoms, and then performing appropriate diagnostic investigations (i.e. genetic testing). ... Combined oxidative phosphorylation deficiency 1: 609060: GFM1: Combined oxidative ...