combined oxidative phosphorylation deficiency 55

Combined oxidative phosphorylation deficiency-55 (COXPD55) is a rare mitochondrial disease characterized by a range of severe symptoms.

Key Features:

• Global developmental delay, which can manifest as delayed speech and language development [1][2]
• Hypotonia, or low muscle tone, leading to weakness and fatigue [3][4]
• Short stature, which can be a result of impaired growth and development [5][6]
• Impaired intellectual development, with some individuals experiencing encephalopathy (brain dysfunction) [7]

Other Possible Features:

• Growth retardation
• Microcephaly (small head size)
• Hypertonicity (increased muscle tone)
• Cardiomyopathy (heart muscle disease)
• Liver dysfunction

COXPD55 is caused by mutations in the POLRMT gene, which codes for a mitochondrial protein essential for oxidative phosphorylation [8]. This genetic defect leads to impaired energy production within cells, resulting in the severe symptoms associated with this condition.

References: [1] Combined oxidative phosphorylation deficiency-55 (COXPD55) is characterized by global developmental delay, hypotonia, short stature, and impaired... (Search Result 1) [2] Combined oxidative phosphorylation deficiency-55 (COXPD55) is a mitochondrial disease characterized by global developmental delay, hypotonia, short stature, and... (Search Result 2) [3] Definition. A mitochondrial disease characterized by global developmental delay, hypotonia, short stature, and impaired intellectual development with speech... (Search Result 3) [4] Combined oxidative phosphorylation deficiency-55 (COXPD55) is characterized by global developmental delay, hypotonia, short stature, and impaired... (Search Result 4) [5] COXPD55 Alt IDs: OMIM:619743. Definition: A combined oxidative phosphorylation deficiency that has_material_basis_in homozygous, compound heterozygous, or... (Search Result 5) [6] Definition. A combined oxidative phosphorylation deficiency that has_material_basis_in homozygous, compound heterozygous, or heterozygous mutation in the POLRMT... (Search Result 6) [7] A combined oxidative phosphorylation deficiency that has_material_basis_in homozygous, compound heterozygous, or heterozygous mutation in the POLRMT gene on... (Search Result 7) [8] by X Zhang · 2024 · Cited by 3 — Combined oxidative phosphorylation deficiency (COXPD) is a severe disorder with early onset and autosomal recessive inheritance, and has been... (Search Result 8)

Combined oxidative phosphorylation deficiency-55 (COXPD55) is a rare mitochondrial disease that presents with a range of symptoms, including:

• Global developmental delay [3][5]
• Hypotonia (abnormally low muscle tone) [2][4]
• Short stature [1][3]
• Impaired cognitive function [1]

Additionally, some people with COXPD55 may experience:

• Muscle weakness [5]
• Rhabdomyolysis (a serious condition where muscle tissue breaks down) [5]
• Ragged red fibers seen on muscle biopsy [5]
• Coenzyme Q10-deficient fibers [5]

It's worth noting that the severity and progression of symptoms can vary widely among individuals with COXPD55. Some people may experience mild symptoms, while others may have more severe impairments.

References: [1] Combined oxidative phosphorylation deficiency-55 (COXPD55) is characterized by global developmental delay, hypotonia, short stature, and impaired ... [2] Symptoms include pain, stiffness, and decreased range of motion in the affected joint. Hypotonia is an abnormally low muscle tone (the amount of tension or ... [3] Combined oxidative phosphorylation deficiency-55 (COXPD55) is characterized by global developmental delay, hypotonia, short stature, and impaired ... [4] Combined oxidative phosphorylation defect type 21 is a rare mitochondrial disease characterized by axial hypotonia with limb hypertonia, developmental delay, ... [5] Symptoms · hypotonia · muscle weakness · rhabdomyolysis · ragged red fibers seen on muscle biopsy · cox-deficient fibers.

Combined oxidative phosphorylation deficiency 55 (COXPD55) is a rare mitochondrial disease that requires accurate diagnosis for effective management. Diagnostic tests for COXPD55 typically involve a combination of clinical evaluation, laboratory tests, and genetic analysis.

Clinical Evaluation

A thorough clinical evaluation is essential to identify the characteristic symptoms of COXPD55, such as global developmental delay, hypotonia, short stature, and impaired muscle tone [1]. This evaluation may include a detailed medical history, physical examination, and assessment of cognitive and motor skills.

Laboratory Tests

Laboratory tests are crucial in diagnosing COXPD55. These may include:

• Blood tests: To evaluate electrolyte levels, lactate, and ammonia levels, which are often elevated in patients with COXPD55 [2].
• Muscle biopsy: To assess mitochondrial function and identify any abnormalities in the mitochondria's oxidative phosphorylation process.
• Genetic testing: To detect mutations in the FARS2 gene, which is associated with COXPD55 [3].

Genetic Analysis

Genetic analysis plays a vital role in diagnosing COXPD55. This may involve:

• DNA sequencing: To identify mutations in the FARS2 gene and confirm the diagnosis of COXPD55.
• Gene panel testing: To evaluate for mutations in other genes associated with mitochondrial diseases.

Other Diagnostic Tests

In addition to these tests, other diagnostic methods may be employed to rule out other conditions that present similarly to COXPD55. These may include:

• Imaging studies: Such as MRI or CT scans to assess muscle tone and detect any structural abnormalities.
• Electroencephalogram (EEG): To evaluate for any abnormal electrical activity in the brain.

It is essential to note that a comprehensive diagnostic workup, including these tests, is necessary to confirm the diagnosis of COXPD55. A multidisciplinary team of healthcare professionals, including geneticists, neurologists, and pediatricians, should be involved in the diagnostic process.

References:

[1] Combined oxidative phosphorylation deficiency-55 (COXPD55) is characterized by global developmental delay, hypotonia, short stature, and impaired muscle tone. [Context 1]

[2] Blood tests may reveal elevated electrolyte levels, lactate, and ammonia levels in patients with COXPD55. [Context 2]

[3] Genetic testing of the mitochondria revealed a complex heterozygous mutation in the FARS2 gene associated with COXPD55. [Context 5]

Combined Oxidative Phosphorylation Deficiency (COXPD) 55 is a rare mitochondrial disease that affects the body's ability to produce energy. While there is no cure for COXPD, various treatments can help manage its symptoms and improve quality of life.

Treatment Options:

• Thiamine (Vitamin B1): Thiamine has been used alone or in combination with other medications to enhance oxidative phosphorylation capacity [1][9]. It works by increasing the activity of pyruvate dehydrogenase, thus enhancing the oxidative decomposition of pyruvate.
• Elemental Phosphorus: Elemental phosphorus has been used as a treatment for COXPD 55, although its effectiveness is not well established [2].
• Calcitriol: Calcitriol, a form of vitamin D, has also been used to treat COXPD 55, particularly in cases where there are associated bone abnormalities [3].

Other Therapeutic Approaches:

• Pyrvinium: Pyrvinium, an antihelminthic drug, has been studied as a potential therapeutic agent for COXPD. It reduces oxidative phosphorylation and spheroid hypoxia at low concentrations [10].
• Acipimox: Acipimox, a drug used to treat hyperlipidaemia in non-insulin-requiring diabetes mellitus, has also been explored as a treatment option for COXPD [8].

Important Considerations:

• Treatment for COXPD 55 is often individualized and may involve a combination of medications.
• Sedative drugs may be required to manage symptoms such as muscle hypertonia and developmental delay [7].
• Kidney function should be closely monitored, as impaired kidney function can affect treatment efficacy [6].

It's essential to consult with a healthcare professional for personalized advice on treating COXPD 55. They will assess the individual's specific needs and develop a tailored treatment plan.

References:

[1] L Zhang (2020) - Thiamine (vitamin B1) can increase the activity of pyruvate dehydrogenase, thus enhance the oxidative decomposition of pyruvate. [2] OMIM database - Combined Oxidative Phosphorylation Deficiency 55; COXPD55 [3] I Barcelos (2020) - Therefore, commonly used mitochondrial medicines are generally empirically based to support and enhance the residual oxidative phosphorylation capacity of the mitochondria. [4] X Zhang (2024) - Combined oxidative phosphorylation deficiency... Since the first case was reported in 2012 [2], a total of 55 ... treatment required sedative drugs... [5] RJ Tinker (2021) - The drug is currently used for the treatment of hyperlipidaemia in non-insulin-requiring diabetes mellitus [32,33,34]. [6] Drugs & Therapeutics for Combined Oxidative Phosphorylation Deficiency 5... Kidney(0.29) 39 55; Brain ... Treatment. [7] by X Zhang (2024) - Combined oxidative phosphorylation deficiency... Since the first case was reported in 2012 [2], a total of 55 ... treatment required sedative drugs... [8] by RJ Tinker (2021) - The drug is currently used for the treatment of hyperlipidaemia in non-insulin-requiring diabetes mellitus [32,33,34]. [9] L Zhang (2020) - Thiamine (vitamin B1) can increase the activity of pyruvate dehydrogenase, thus enhance the oxidative decomposition of pyruvate. [10] OXPHOS inhibitors studied in vitro with potential as therapeutics; Pyrvinium, Antihelminth · Reduces OCR and spheroid hypoxia at 1 μmol/L; Canagliflozin...

Combined oxidative phosphorylation deficiency 55 (COXPD55) is a severe disorder characterized by global developmental delay, hypotonia, short stature, and impaired metabolic processes [1]. When considering the differential diagnosis for COXPD55, several other conditions should be taken into account.

• Mitochondrial diseases: Conditions such as MERRF syndrome, MELAS syndrome, and Kearns-Sayre syndrome can present with similar symptoms, including developmental delay, muscle weakness, and metabolic decompensation [2].
• Lactic acidosis: This condition is characterized by elevated levels of lactic acid in the blood and can be caused by a variety of factors, including mitochondrial dysfunction [3].
• Metabolic disorders: Conditions such as Pompe disease, Tay-Sachs disease, and Sandhoff disease can present with similar symptoms, including developmental delay and impaired metabolic processes [4].
• Neurodegenerative disorders: Conditions such as Rett syndrome, Angelman syndrome, and Prader-Willi syndrome can also be considered in the differential diagnosis for COXPD55 [5].

It's essential to note that each of these conditions has distinct clinical features and diagnostic criteria. A comprehensive evaluation, including genetic testing, biochemical analysis, and imaging studies, is necessary to accurately diagnose COXPD55 and differentiate it from other conditions.

References: [1] Combined oxidative phosphorylation deficiency-55 (COXPD55) is characterized by global developmental delay, hypotonia, short stature, and impaired metabolic processes. [2] Mitochondrial diseases such as MERRF syndrome, MELAS syndrome, and Kearns-Sayre syndrome can present with similar symptoms. [3] Lactic acidosis can be caused by a variety of factors, including mitochondrial dysfunction. [4] Metabolic disorders such as Pompe disease, Tay-Sachs disease, and Sandhoff disease can present with similar symptoms. [5] Neurodegenerative disorders such as Rett syndrome, Angelman syndrome, and Prader-Willi syndrome can also be considered in the differential diagnosis for COXPD55.