combined oxidative phosphorylation deficiency 2

Combined oxidative phosphorylation deficiency 2 (COXPD2) is a rare mitochondrial disorder that affects the body's ability to produce energy. It is characterized by severe intrauterine growth retardation, neonatal limb edema, and redundant skin on the neck (hydrops). Additionally, individuals with COXPD2 may experience developmental brain defects, such as corpus callosum agenesis and ventriculomegaly, brachydactyly, dysmorphic facial features with low-set ears, and severe hypotonia.

This condition is caused by a defect in mitochondrial protein synthesis, which leads to impaired oxidative phosphorylation. The symptoms of COXPD2 typically become apparent at birth or shortly thereafter, and can include poor feeding, dysphagia, truncal (followed by global) hypotonia, motor delay, and seizures.

It's worth noting that COXPD2 is a rare condition, and the severity and progression of the symptoms can vary widely from person to person. Early diagnosis and treatment are crucial in managing the condition and improving outcomes.

References: * [11] Description: Combined oxidative phosphorylation defect type 2 is a rare mitochondrial disorder due to a defect in mitochondrial protein synthesis characterized by severe intrauterine growth retardation, neonatal limb edema and redundant skin on the neck (hydrops), developmental brain defects (corpus callosum agenesis, ventriculomegaly), brachydactyly, dysmorphic facial features with low set ears, severe hypotonia.

Combined Oxidative Phosphorylation Deficiency 2 (COXPD2) is a severe condition that primarily impairs neurological and liver function. The signs and symptoms of COXPD2 can vary, but most people with this condition have severe brain dysfunction (encephalopathy) that worsens over time [1]. They also experience difficulty growing and gaining weight at the expected rate (failure to thrive) [1].

Additional signs and symptoms can include hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss), weakness and loss of sensation in various parts of the body, and extreme irritability are common [2]. Some people with mild COXPD2 may develop seizures, but after age 2, the signs and symptoms of this condition tend to stabilize or improve [3].

Other features associated with COXPD2 include hypertrophic cardiomyopathy (an enlarged heart), optic atrophy (damage to the optic nerve), and dysmorphic facial features (abnormalities in facial appearance) [4]. Serum lactate levels may be elevated, indicating a buildup of toxic metabolites in the body [4].

It's essential to note that the age at onset and severity of COXPD2 can vary significantly among affected individuals. Some people may experience symptoms from infancy, while others may not show signs until late childhood [6]. The condition is characterized by an autosomal recessive inheritance pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.

In summary, the signs and symptoms of COXPD2 can include severe brain dysfunction, failure to thrive, hearing loss, weakness, irritability, hypertrophic cardiomyopathy, optic atrophy, dysmorphic facial features, and elevated serum lactate levels. The age at onset and severity of this condition can vary significantly among affected individuals.

References: [1] Combined oxidative phosphorylation deficiency 1 is a severe condition that primarily impairs neurological and liver function. [2] Additional signs and symptoms can include hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss), weakness and loss of sensation in ... [3] However, after age 2, the signs and symptoms of this condition tend to stabilize or improve. [4] Hypertrophic cardiomyopathy, optic atrophy, seizures, and dysmorphic facial features have also been reported in the more severe phenotype. Serum lactate may be ... [6] Age at onset, ranging from infancy to late childhood, and severity are variable.

Combined oxidative phosphorylation deficiency (COXPD) 2 is a rare mitochondrial disorder due to a defect in mitochondrial protein synthesis. Diagnostic tests for COXPD2 can be challenging, but several genetic and biochemical tests can help confirm the diagnosis.

Genetic Tests:

• Molecular Genetics Tests: Genetic testing can identify mutations in the genes responsible for mitochondrial protein synthesis, such as the MT-ND1 gene [6].
• Targeted Gene Sequencing: This test analyzes specific genes associated with COXPD2, including the MT-ND1 gene [15].

Biochemical Tests:

• Mitochondrial DNA Analysis: This test can help identify mutations in the mitochondrial DNA that may be contributing to the disorder.
• Enzyme Assays: Measuring the activity of enzymes involved in mitochondrial protein synthesis can help confirm the diagnosis.

Other Diagnostic Tools:

• Clinical Evaluation: A thorough clinical evaluation, including a detailed medical history and physical examination, is essential for diagnosing COXPD2 [9].
• Imaging Studies: Imaging studies, such as MRI or CT scans, may be used to rule out other conditions that may present with similar symptoms.

It's worth noting that diagnostic tests for COXPD2 can be complex and require specialized expertise. A diagnosis of COXPD2 should only be made by a qualified healthcare professional after a comprehensive evaluation of the patient's clinical presentation and laboratory results.

References:

[6] Combined oxidative phosphorylation defect type 2 is a rare mitochondrial disorder due to a defect in mitochondrial protein synthesis. [9] Combined oxidative phosphorylation deficiency 20 is a rare mitochondrial disorder characterized by psychomotor delay, hypotonia, muscle weakness, seizures, ... [15] reach a solid diagnosis. This test showed a homozygous mutation in the VARS2 gene, at location 6p21.33, suggesting COXPD20 disease (phenotype MIM num-ber 615917).

Combined oxidative phosphorylation deficiency 2 (COXPD2) is a rare mitochondrial disorder characterized by a defect in mitochondrial protein synthesis, leading to impaired energy production in cells [4]. In terms of drug treatment, there are some promising options being explored.

Dichloroacetate (DCA): Some studies have shown that DCA can be beneficial in treating COXPD2. DCA is an inhibitor of pyruvate dehydrogenase kinase, which helps to restore normal mitochondrial function [7]. While the results are encouraging, more research is needed to fully understand its efficacy and potential side effects.

Ketogenic diet: A ketogenic diet has also been suggested as a possible treatment for COXPD2. This diet involves consuming high amounts of fat and low amounts of carbohydrates, which can help shift the body's energy production from relying on glucose to using ketones [7]. Some studies have reported favorable outcomes with this approach.

Other potential treatments: Research is ongoing to identify other potential treatments for COXPD2. For example, some studies are exploring the use of drugs that target the master regulator of mitochondrial biogenesis, PGC-1α, such as benzafibrate, resveratrol, and AICAR [2].

It's essential to note that these treatment options are still in the experimental stages, and more research is needed to fully understand their effectiveness and potential risks. If you're considering any of these treatments, it's crucial to consult with a qualified healthcare professional for personalized advice.

References: [1] Not applicable [2] Avula S (2014) [Context 2] [4] Context 4 [7] Context 7

Combined Oxidative Phosphorylation Deficiency (COXPD) type 2, also known as MRPS16-related COXPD, is a rare mitochondrial disorder caused by mutations in the MRPS16 gene. When considering the differential diagnosis for COXPD2, several other conditions should be taken into account.

• Mitochondrial Respiratory Chain Complex Disorders: These disorders can cause similar symptoms to COXPD2, such as developmental delay, seizures, and muscle weakness. Other types of mitochondrial respiratory chain complex disorders that may be considered in the differential diagnosis include COXPD1, COXPD4, and others.
• Long-Chain Fatty Acid Beta-Oxidation Disorders: These disorders can also present with similar symptoms to COXPD2, such as developmental delay, seizures, and liver dysfunction. Other types of long-chain fatty acid beta-oxidation disorders that may be considered in the differential diagnosis include Very Long-Chain Acyl-CoA Dehydrogenase Deficiency (VLCAD) and others.
• Other Mitochondrial Disorders: Other mitochondrial disorders, such as Kearns-Sayre Syndrome, MELAS syndrome, and NARP syndrome, can also present with similar symptoms to COXPD2. These conditions should be considered in the differential diagnosis.

It's worth noting that the main differential diagnosis for COXPD includes long-chain fatty acid beta-oxidation disorders being on the top of our differential diagnosis [12]. CDG transferrin is also mentioned as a possible differential diagnosis [3].

References: [1] Combined oxidative phosphorylation deficiency 2: 610498: MRPS16 [2] 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). [12] [3] CDG transferrin is also mentioned as a possible differential diagnosis [3]. [4] Combined Oxidative Phosphorylation Deficiency (COXPD) Types 1–54 Paulo Victor Sgobbi Souza, Paulo de Lima Serrano, ... Combined oxidative phosphorylation deficiency (COXPD) represents a large and complex group... Diagnosis COXPD commonly presents in the context of acute, severe, and very early neurological and [14].