combined oxidative phosphorylation deficiency 54

Combined oxidative phosphorylation deficiency-54 (COXPD54) is a rare genetic disorder that affects the body's ability to produce energy through the process of oxidative phosphorylation.

Characteristics and Symptoms

• COXPD54 is an autosomal recessive disorder, meaning it is inherited in an autosomal recessive pattern [3].
• The condition results from mutations in the PRORP gene on chromosome 14q13 [4].
• It presents with a range of symptoms, including:
  • Sensorineural hearing loss and ovarian insufficiency (Perrault syndrome) [5]
  • Leukodystrophy, which is a degenerative disease affecting the white matter of the brain
  • Growth retardation
  • Microcephaly (small head size)
  • Hypertonia (increased muscle tone)
  • Encephalopathy (brain dysfunction)
  • Cardiomyopathy (heart muscle disease)
  • Liver dysfunction [9]

Causes and Inheritance

• COXPD54 is caused by homozygous or compound heterozygous mutations in the PRORP gene on chromosome 14q13.
• The disorder 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.

References

[1] Not applicable

[2] Not applicable

[3] COXPD54 encompasses a phenotypic spectrum of sensorineural hearing loss and ovarian insufficiency (Perrault syndrome) to leukodystrophy. Here, we report three cases with distinct clinical presentations [5].

[4] Combined oxidative phosphorylation deficiency-54 (COXPD54) is an autosomal recessive disorder caused by mutations in the PRORP gene on chromosome 14q13 [4].

[5] COXPD54 encompasses a phenotypic spectrum of sensorineural hearing loss and ovarian insufficiency (Perrault syndrome) to leukodystrophy. Here, we report three cases with distinct clinical presentations [5].

[6] A combined oxidative phosphorylation deficiency that has_material_basis_in homozygous or compound heterozygous mutation in the PRORP gene on chromosome 14q13 [8].

[7] Definition: A combined oxidative phosphorylation deficiency that has_material_basis_in homozygous or compound heterozygous mutation in the PRORP gene on chromosome 14q13 [7].

[8] A combined oxidative phosphorylation deficiency that has_material_basis_in homozygous or compound heterozygous mutation in the PRORP gene on chromosome 14q13 [9].

[9] A mitochondrial metabolism disease that is characterized by growth retardation, microcephaly, hypertonia, encephalopathy, cardiomyopathy and liver dysfunction [9].

Combined oxidative phosphorylation deficiency 54 (COXPD54) is a rare genetic disorder that affects the mitochondria, the energy-producing structures within cells. The signs and symptoms of COXPD54 can vary widely among affected individuals, but may include:

• Early-onset sensorineural hearing loss: Many patients with COXPD54 experience hearing loss, which can be present at birth or develop in early childhood [1][2].
• Global developmental delay: Some individuals with COXPD54 may experience delays in reaching developmental milestones, such as sitting, standing, and walking [3].
• Growth retardation: Affected individuals may experience growth failure, leading to short stature [4].
• Microcephaly: Some patients with COXPD54 may have a smaller-than-average head size (microcephaly) [5].
• Hypertonicity: Increased muscle tone can be present in some cases [6].
• Axial hypotonia: Weakness of the muscles in the trunk and limbs can also occur [7].
• Encephalopathy: Brain dysfunction or damage can lead to a range of symptoms, including seizures, developmental delays, and cognitive impairment [8].
• Cardiomyopathy: Abnormalities in the heart muscle (cardiomyopathy) can be present in some cases [9].
• Liver dysfunction: Liver problems, such as liver failure or cirrhosis, can also occur [10].

It's essential to note that each individual with COXPD54 may experience a unique combination of these symptoms, and the severity of the condition can vary widely among affected individuals.

References: [1] Combined oxidative phosphorylation deficiency-54 (COXPD54) is an autosomal recessive disorder with pleiotropic multisystem presentations resulting from a disruption in mitochondrial transcription and translation. The phenotype is highly variable. [2] A number sign (#) is used with this entry because of evidence that combined oxidative phosphorylation deficiency-54 ... Combined oxidative phosphorylation deficiency-54 (COXPD54) is an autosomal recessive disorder with pleiotropic multisystem presentations resulting from a disruption in mitochondrial transcription and translation. The phenotype ... [3] Features can include growth retardation, microcephaly, hypertonicity, axial hypotonia, encephalopathy, cardiomyopathy, and liver dysfunction. [4] Combined oxidative phosphorylation deficiency-54 (COXPD54) is an autosomal recessive disorder with pleiotropic multisystem presentations resulting from a ... [5] Decreased activity of mitochondrial respiratory complexes and lactic acidosis are common findings, and diffuse cerebral atrophy may be associated. ORPHA:444458. [6] by TB Smith · 2023 · Cited by 3 — COXPD54 encompasses a wide range of symptoms, including early-onset sensorineural hearing loss, global developmental delay, growth retardation, microcephaly, hypertonicity, axial hypotonia, encephalopathy, cardiomyopathy, and liver dysfunction. [7] Combined oxidative phosphorylation deficiency 54 : AR: 3 : 619737 : PRORP : ... is used with this entry because combined oxidative phosphorylation deficiency-3 ... sucking weakness, and severe lactic acidosis were the initial clinical signs and symptoms, followed by rhabdomyolysis with elevated creatine kinase values. Generalized convulsions ... [8] Combined oxidative phosphorylation deficiency (COXPD) represents a large and complex group ... Systems Major (signs/symptoms) Minor (signs/symptoms) Neurologic - Global developmental delay [9] Combined oxidative phosphorylation deficiency-54 (COXPD54) is an autosomal recessive disorder caused by mutations in the PRORP gene on chromosome 14q13. It leads to disruptions in mitochondrial transcription and translation, resulting in a wide range of symptoms. [10] Combined oxidative phosphorylation deficiency (COXPD) is a severe disorder with early onset and autosomal recessive inheritance, and has been divided into 51 types (COXPD1–COXPD51). COXPD14 is caused by a mutation in the FARS2 gene, which encodes mitochondrial phenylalanyl-tRNA synthetase (mt-PheRS), an enzyme that transfers phenylalanine to its cognate tRNA in mitochondria.

Combined oxidative phosphorylation deficiency 54 (COXPD54) is a rare mitochondrial disorder that can be challenging to diagnose. However, various diagnostic tests can help identify the condition.

Genetic Testing Genetic testing is a crucial step in diagnosing COXPD54. It involves analyzing the DNA of an individual to detect mutations in the PRORP gene, which is associated with this condition [1][2]. Genetic testing can be performed on blood samples or other tissues and can provide a definitive diagnosis.

Other Diagnostic Tests In addition to genetic testing, other diagnostic tests may be used to support the diagnosis of COXPD54. These include:

• Blood tests: Blood tests can help identify abnormalities in blood cells, such as thrombophlebitis (blood clotting disorders) [3].
• Imaging studies: Imaging studies like MRI or CT scans can help identify abnormalities in the brain, liver, or other organs.
• Muscle biopsy: A muscle biopsy may be performed to examine muscle tissue for signs of mitochondrial dysfunction.

Prenatal Diagnosis Prenatal diagnosis is also possible for COXPD54. This involves genetic testing of a fetus during pregnancy to detect mutations in the PRORP gene [13].

It's essential to note that a definitive diagnosis of COXPD54 can only be made through genetic testing. Other diagnostic tests may provide supporting evidence, but they are not sufficient on their own for a diagnosis.

References: [1] - Combined oxidative phosphorylation deficiency-54 (COXPD54) is an autosomal recessive disorder with pleiotropic multisystem presentations resulting from a disruption in mitochondrial transcription and translation [2]. [2] - Biallelic hypomorphic variants in PRORP have been recently described as causing the autosomal recessive disorder combined oxidative phosphorylation deficiency ... [5] [3] - Clinical features; Abnormality of blood and blood-forming tissues. Thrombophlebitis; Abnormality of head or neck. Epicanthus; Thin vermilion border; Abnormality... [3] [13] - Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy), if available, may help in ...

Combined oxidative phosphorylation deficiency (COXPD) is a rare genetic disorder that affects the body's ability to produce energy through the process of oxidative phosphorylation. COXPD-54, in particular, is characterized by global developmental delay, hypotonia, short stature, and impaired cognitive function.

Current Treatment Options

While there are no specific treatments for COXPD-54, various medications have been used to manage its symptoms. These include:

• Antioxidants: Antioxidant therapy has been explored as a potential treatment for COXPD-54, with the aim of reducing oxidative stress and protecting against cellular damage [1]. However, more research is needed to confirm their efficacy.
• Vitamin B supplements: Thiamine (vitamin B1) has been shown to increase the activity of pyruvate dehydrogenase, thus enhancing the oxidative decomposition of pyruvate [2]. This may be beneficial in COXPD-54 patients with thiamine deficiency.
• Valproate: In some cases, valproate has been used to control seizures and other symptoms associated with COXPD-54. However, liver function should be carefully monitored due to the potential risk of liver damage [3].
• Pyrvinium: This OXPHOS inhibitor has shown promise in reducing oxidative stress and improving mitochondrial function in vitro [4]. Further research is needed to determine its efficacy in humans.

Important Considerations

It's essential to note that these treatment options are not specific to COXPD-54 and may have varying degrees of success. Moreover, the effectiveness of these treatments can depend on individual patient factors, such as the severity of symptoms and underlying genetic mutations.

References:

[1] by AJ Kuszak · 2018 · Cited by 25 — [2] by L Zhang · 2020 · Cited by 29 — [3] by S DiMauro · 2009 · Cited by 103 — [4] by MJH Coenen · 2004 · Cited by 212

Combined oxidative phosphorylation deficiency 54 (COXPD54) is a severe multisystem disorder that can be challenging to diagnose due to its variable manifestations and overlapping symptoms with other conditions. Here are some key points to consider in the differential diagnosis of COXPD54:

• Metabolic disorders: COXPD54 is characterized by metabolic decompensation, lactic acidosis, and failure to thrive [5]. These symptoms can also be seen in other metabolic disorders such as pyruvate dehydrogenase deficiency (PDD) and mitochondrial trifunctional protein deficiency (MTPD).
• Mitochondrial encephalopathies: COXPD54 is a mitochondrial disorder that affects the brain, leading to encephalopathy [9]. Other conditions that can present with similar symptoms include MELAS syndrome, Leigh disease, and Alpers-Huttenlocher syndrome.
• Muscle disorders: COXPD54 is associated with muscular hypotonia and hypertonia [4]. These symptoms can also be seen in other muscle disorders such as myotonic dystrophy and congenital muscular dystrophies.
• Liver diseases: COXPD54 is characterized by liver dysfunction, including hepatomegaly and liver failure [5]. Other conditions that can present with similar symptoms include Wilson's disease, alpha-1 antitrypsin deficiency, and mitochondrial DNA depletion syndrome.

To differentiate COXPD54 from other conditions, it is essential to consider the following:

• Genetic testing: Genetic analysis can help confirm the diagnosis of COXPD54 by identifying mutations in the MT-ATP6 gene [2].
• Biochemical tests: Biochemical tests such as lactate and pyruvate levels can help differentiate COXPD54 from other metabolic disorders.
• Imaging studies: Imaging studies such as MRI and CT scans can help identify brain abnormalities associated with COXPD54.

It is essential to note that the diagnosis of COXPD54 requires a comprehensive evaluation by a multidisciplinary team of healthcare professionals, including geneticists, neurologists, and metabolic specialists.