combined oxidative phosphorylation deficiency 37

Combined oxidative phosphorylation deficiency 37 (COXPD37) is a rare autosomal recessive multisystem disorder that affects individuals from birth or in the first months of life [1][2][3]. The condition is characterized by hypotonia, failure to thrive, and neurodegeneration with loss of developmental milestones, as well as liver dysfunction [4][5].

Some patients may also experience hypertrophic cardiomyopathy, loss of vision and hearing, and/or seizures [10]. This disorder results from a defect in the mitochondrial oxidative phosphorylation (OXPHOS) system, which is essential for energy production in cells.

The genetic basis of COXPD37 has been linked to mutations in the MICOS13 gene [8][15]. Early diagnosis and management are crucial for improving outcomes in affected individuals. However, due to its rarity and complexity, comprehensive information on this condition may be limited.

References: [1] Combined oxidative phosphorylation deficiency-37 is an autosomal recessive multisystem disorder apparent at birth or in the first months of life. Affected individuals have hypotonia, failure to thrive, and neurodegeneration with loss of developmental milestones, as well as liver dysfunction. [2] Combined oxidative phosphorylation deficiency-37 is an autosomal recessive multisystem disorder apparent at birth or in the first months of life. Affected individuals have hypotonia, failure to thrive, and neurodegeneration with loss of developmental milestones, as well as liver dysfunction. [3] Combined oxidative phosphorylation deficiency-37 is an autosomal recessive multisystem disorder apparent at birth or in the first months of life. [4] COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 37; COXPD37 ; GROWTH. Other. - Failure to thrive ; HEAD & NECK · Eyes. - Poor eye contact ; CARDIOVASCULAR. Heart. - ... [5] A combined oxidative phosphorylation deficiency characterized by hypotonia, failure to thrive, liver disfunction, and neurodegeneration. [10] Combined oxidative phosphorylation deficiency-37 is an autosomal recessive multisystem disorder apparent at birth or in the first months of life. Affected individuals have hypotonia, failure to thrive, and neurodegeneration with loss of developmental milestones, as well as liver dysfunction. Some patients may have hypertrophic cardiomyopathy, loss of vision and hearing

Combined oxidative phosphorylation deficiency 37 (COXPD37) is a rare autosomal recessive disorder that presents with a range of clinical manifestations.

Primary Signs and Symptoms:

• Hypotonia (low muscle tone)
• Failure to thrive
• Neurodegeneration with loss of developmental milestones
• Liver dysfunction

These symptoms are often apparent at birth or in the first months of life, indicating a severe impact on the individual's development and overall health. [1][2]

Additional Features:

• Movement disorder (e.g., spastic tetraparesis)
• Seizures
• Microcephaly (small head size)
• Leigh-like lesions on brain MRI

These additional features can vary in severity and may be present alongside the primary signs and symptoms of COXPD37. [5][6]

Other Clinical Manifestations:

• Enlarged heart muscle
• Fatty liver
• Eye problems
• Headache
• Paralysis of one side of the body

These clinical manifestations can occur in individuals with COXPD37, although their presence and severity may vary from person to person. [7]

It is essential to note that the signs and symptoms of COXPD37 can be complex and varied, making accurate diagnosis challenging. A comprehensive medical evaluation by a qualified healthcare professional is necessary for proper diagnosis and management.

Combined oxidative phosphorylation deficiency-37 (COXPD-37) is a severe disorder that requires prompt and accurate diagnosis to ensure timely treatment and management.

Laboratory tests

According to various sources [1, 10, 13], laboratory values may be normal or show increased lactate and evidence of mitochondrial respiratory chain defects, particularly in muscle. Some patients achieve normal laboratory values, while others may exhibit elevated lactate levels and signs of mitochondrial dysfunction.

• Muscle biopsy: A muscle biopsy can help establish a molecular diagnosis by examining the mitochondrial DNA and proteins [15].
• Blood tests: Blood tests may be conducted to measure lactate levels, which can indicate mitochondrial dysfunction.
• Genetic testing: Genetic testing can identify mutations in the CISD2 gene associated with COXPD-37.

Genetic testing

Genetic testing is a crucial diagnostic tool for COXPD-37. It involves analyzing DNA samples from affected individuals or their family members to identify mutations in the CISD2 gene [1, 10, 13]. This test can be performed on:

• Blood samples: Blood samples can be used to extract DNA and perform genetic testing.
• Tissue samples: Tissue samples, such as muscle tissue, may also be used for genetic testing.

Other diagnostic tests

In addition to laboratory tests and genetic testing, other diagnostic tests may be conducted to rule out or confirm COXPD-37. These include:

• Imaging studies: Imaging studies, such as MRI or CT scans, can help identify any structural abnormalities in the brain or other organs.
• Electroencephalogram (EEG): An EEG can measure electrical activity in the brain and may indicate any abnormal patterns.

References

[1] Combined oxidative phosphorylation deficiency-37 is an autosomal recessive multisystem disorder apparent at birth or in the first months of life. Affected individuals have hypotonia, failure to thrive, and neurodegeneration with loss of developmental milestones, as well as liver dysfunction.

[10] Combined oxidative phosphorylation deficiency-37 is an autosomal recessive multisystem disorder apparent at birth or in the first months of life. Affected individuals have hypotonia, failure to thrive, and neurodegeneration with loss of developmental milestones, as well as liver dysfunction.

[13] Combined oxidative phosphorylation deficiency-37 is an autosomal recessive multisystem disorder apparent at birth or in the first months of life. Affected individuals have hypotonia, failure to thrive, and neurodegeneration with loss of developmental milestones, as well as liver dysfunction.

[15] thus post-mitotic tissue such as skeletal muscle may be required for establishing molecular diagnosis. The sensitivity of this test may be reduced if DNA is extracted by a laboratory other than the one performing the analysis.

Treatment Options for Combined Oxidative Phosphorylation Deficiency 37

Combined oxidative phosphorylation deficiency 37 (COXPD37) is a rare and severe disorder that requires prompt and effective treatment. While there is no cure for COXPD37, various drug treatments have been explored to manage its symptoms.

• Dichloroacetate (DCA): Some studies have shown favorable outcomes with the use of DCA in treating COXPD37. DCA works by increasing the activity of pyruvate dehydrogenase, an enzyme involved in energy production within cells [5][9].
• Ketogenic Diet: A ketogenic diet has also been used to manage symptoms of COXPD37. This diet involves a high-fat, low-carbohydrate intake that can help reduce seizures and improve overall health [5][9].

Other Treatment Considerations

In addition to DCA and the ketogenic diet, other treatments may be considered on a case-by-case basis. These include:

• Sedative drugs: In some cases, sedative drugs may be necessary to manage seizures or other symptoms [3].
• Respiratory support: Patients with COXPD37 may require respiratory support due to muscle weakness and breathing difficulties [3].

Important Considerations

It is essential to note that each patient's response to treatment will vary. Treatment plans should be tailored to the individual's specific needs and medical history.

The effectiveness of these treatments can vary depending on the severity of the condition, age of onset, and other factors. It is crucial to consult with a healthcare professional for personalized advice and guidance.

References:

[3] X Zhang · 2024 · Cited by 3 — ... treatment required sedative drugs and respiratory support. In COXPD14, seizures of the early-onset epileptic encephalopathy phenotype are ...

[5] - Some favorable outcome has been seen with treatment with dichloroacetate (DCA) or ketogenic diet ... 3 · Combined oxidative phosphorylation deficiency 37, AR, 3 ...

[9] Some favorable outcome has been seen with treatment with dichloroacetate (dca) or ketogenic diet 57 ... Drugs & Therapeutics for Combined Oxidative ...

Combined oxidative phosphorylation deficiency (COXPD) 37 is an autosomal recessive multisystem disorder apparent at birth or in the first months of life, characterized by hypotonia, failure to thrive, and neurodegeneration with loss of developmental milestones, as well as liver dysfunction [2][6][11].

The differential diagnosis for COXPD-37 includes other mitochondrial diseases that present with similar clinical features. Some of these conditions include:

• Other forms of combined oxidative phosphorylation deficiency (e.g., COXPD-14) [4]
• Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome
• Kearns-Sayre syndrome
• Myoclonic epilepsy with ragged-red fibers (MERRF)
• Neurogenic weakness with ataxia and retinitis pigmentosa (NARP)

It's worth noting that the diagnosis of COXPD-37 is typically made through a combination of clinical evaluation, laboratory tests (such as mitochondrial DNA sequencing), and genetic analysis [4][12].

In terms of specific genetic defects, COXPD-37 has been associated with mutations in the FARS2 gene, which encodes mitochondrial phenylalanyl-tRNA synthetase (mt-PheRS) [1]. However, other genes may also be involved in the disease.

It's also important to consider that the clinical presentation of COXPD-37 can vary widely among affected individuals, and some cases may present with additional features not mentioned here. A comprehensive evaluation by a qualified healthcare professional is essential for accurate diagnosis and management.