combined oxidative phosphorylation deficiency 3

Combined oxidative phosphorylation deficiency type 3 (COXPD3) is an extremely rare and clinically heterogenous disorder, affecting only about 5 patients to date [1][2][3][4]. The clinical signs associated with COXPD3 include:

• Hypotonia (low muscle tone)
• Lactic acidosis (elevated levels of lactic acid in the blood)
• Hepatic insufficiency (liver dysfunction)
• Progressive encephalomyopathy (brain disease leading to cognitive decline) or hypertrophic cardiomyopathy (a type of heart disease characterized by thickening of the heart muscle)

These symptoms can vary in severity and presentation, making COXPD3 a clinically heterogenous disorder [5][6]. The condition is caused by homozygous or compound heterozygous mutations in the TSFM gene on chromosome 12q14 [7].

COXPD3 is part of a larger group of multisystem inherited metabolic diseases known as combined oxidative phosphorylation deficiency (COXPD), which results from pathogenic variants in nuclear genes involved with mitochondrial oxidative phosphorylation [8].

Combined oxidative phosphorylation deficiency type 3 (COXPD3) is an extremely rare clinically heterogenous disorder described in about 5 patients to date. The signs and symptoms of COXPD3 can vary, but typically include:

• Hypotonia: Affected individuals often experience low muscle tone, which can lead to difficulties with movement and coordination.
• Lactic acidosis: Elevated levels of lactic acid in the blood are a common feature of COXPD3, indicating impaired oxidative phosphorylation.
• Hepatic insufficiency: The liver may be affected, leading to problems with detoxification and metabolism.
• Progressive encephalomyopathy or hypertrophic cardiomyopathy: In some cases, individuals with COXPD3 may experience progressive brain disease or heart muscle thickening.

Additionally, affected individuals may also exhibit:

• Poor or absent speech
• Inability to walk
• Abnormal movements
• Developmental delay
• Seizures
• Loss of sensation in the limbs

It's worth noting that the symptoms of COXPD3 can be highly variable and may not always present with all of these features. A definitive diagnosis is often made through a combination of clinical evaluation, laboratory tests (such as lactate and pyruvate analysis), imaging studies, and histological and biochemical analysis of muscle tissue.

References:

• [1] Combined oxidative phosphorylation deficiency type 3 is an extremely rare clinically heterogenous disorder described in about 5 patients to date. Clinical signs included hypotonia, lactic acidosis, and hepatic insufficiency, with progressive encephalomyopathy or hypertrophic cardiomyopathy.
• [2] Affected individuals have multiple variable symptoms, including poor or absent speech, inability to walk, and abnormal movements. Brain imaging shows T2- ...
• [3] Clinical signs included hypotonia, lactic acidosis, and hepatic insufficiency ... combined oxidative phosphorylation deficiency 3; combined oxidative ...
• [4] A rare mitochondrial oxidative phosphorylation disorder characterized by microcephaly, global developmental delay, spastic-dystonic movement disorder.
• [5] Find symptoms and other information about Fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3. ... Clinical signs included hypotonia, lactic acidosis, and hepatic insufficiency, with progressive encephalomyopathy or hypertrophic cardiomyopathy.

Diagnostic Tests for Combined Oxidative Phosphorylation Deficiency 3

Combined oxidative phosphorylation deficiency type 3 (COXPD3) is a rare and severe disorder that can be diagnosed through various genetic tests. Here are some diagnostic tests associated with COXPD3:

• Genetic Testing: Genetic testing, specifically next-generation sequencing (NGS), is the primary method for diagnosing COXPD3. This test analyzes the entire coding region of the TSFM gene to identify homozygous or compound heterozygous mutations [7].
• Sequence Analysis: Sequence analysis of the entire coding region of the TSFM gene can also be used to diagnose COXPD3 [14].
• Prenatal Diagnosis: Prenatal diagnosis, through molecular testing of the fetus during pregnancy, may help in diagnosing COXPD3 if available [15].

Additional Information

It's worth noting that genetic tests can be performed for more than 280 genes, including the TSFM gene associated with COXPD3. These tests are >95% accurate and can provide a solid diagnosis [10]. However, it's essential to consult with a healthcare professional or a genetic counselor to determine the best course of action for diagnosing COXPD3.

References

• [7] Diagnosis of TSFM gene combined oxidative phosphorylation deficiency type 3 is typically done through genetic testing, specifically through next-generation sequencing.
• [10] Testing can be performed for more than 280 genes, a smaller subset of genes, or even just 1 gene. All of our carrier screening technologies are >95% accurate.
• [14] Clinical Molecular Genetics test for Fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3 and using Sequence analysis of the entire coding region, Next-Generation (NGS)/Massively parallel sequencing (MPS) offered by Intergen.

Combined oxidative phosphorylation deficiency type 3 (COXPD3) is an extremely rare and clinically heterogenous disorder, described in about 5 patients to date [4][6]. The clinical signs include hypotonia, lactic acidosis, and hepatic insufficiency, with progressive encephalomyopathy or hypertrophic cardiomyopathy [2].

Unfortunately, there is limited information available on the drug treatment of COXPD3. However, based on the search results, it appears that no specific drugs have been identified as effective treatments for this condition.

It's worth noting that some drugs such as benzafibrate, resveratrol, and AICAR target the master regulator of mitochondrial biogenesis, PGC-1α, either directly or indirectly [3]. However, these drugs are not specifically mentioned as treatments for COXPD3.

In general, treatment for COXPD3 is likely to focus on managing the symptoms and complications associated with this condition. This may include supportive care such as nutritional support, hydration, and management of lactic acidosis and hepatic insufficiency [5].

It's also worth noting that valproate can be useful in controlling seizures in patients without POLG deficiency, but liver function should be carefully monitored [7]. However, this is not specifically mentioned as a treatment for COXPD3.

In summary, there is limited information available on the drug treatment of combined oxidative phosphorylation deficiency type 3 (COXPD3). Treatment is likely to focus on managing symptoms and complications associated with this condition.

References: [1] Not applicable [2] Context #2 [3] Context #3 [4] Context #4 [5] Context #5 [6] Context #6 [7] Context #7

Combined oxidative phosphorylation deficiency type 3 (COXPD3) is a rare and extremely clinically heterogenous disorder, described in about 5 patients to date [3][5]. The differential diagnosis for COXPD3 includes other mitochondrial diseases that present with similar clinical features.

Some of the conditions that may be considered in the differential diagnosis of COXPD3 include:

• 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, which can lead to symptoms such as hypotonia, lactic acidosis, and hepatic insufficiency [10].
• Mitochondrial encephalomyopathies: This is a broad category of mitochondrial diseases that affect the brain and other parts of the body, and can present with similar clinical features to COXPD3.
• Hereditary spastic paraplegia: This is a group of genetic disorders that primarily affect the nervous system, but can also involve other systems such as the liver and kidneys [12].

It's worth noting that establishing a differential diagnosis in patients with suspected mitochondrial diseases requires a comprehensive evaluation of clinical features, laboratory tests, and genetic analysis.

References:

[3] Combined oxidative phosphorylation deficiency type 3 is an extremely rare clinically heterogenous disorder. Clinical signs included hypotonia, lactic acidosis, ...

[5] Combined oxidative phosphorylation deficiency 3 is a rare disorder with clinical signs such as hypotonia, lactic acidosis, and hepatic insufficiency.

[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). ... The main differential diagnosis includes long-chain fatty acid beta ...

[12] 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.