combined oxidative phosphorylation deficiency 9

Combined oxidative phosphorylation deficiency 9 (COXPD9) is a rare mitochondrial disease characterized by a defect in mitochondrial protein synthesis [1]. This condition is marked by initially normal growth and development, followed by symptoms such as failure to thrive, poor feeding, hypertrophic cardiomyopathy, hepatomegaly, and psychomotor retardation [2][7].

The disease is caused by mutations in the MRPL3 gene on chromosome 17, which encodes a protein involved in mitochondrial protein synthesis [9]. These mutations lead to impaired energy production within mitochondria, resulting in the observed symptoms.

COXPD9 is a severe condition that can have significant consequences for affected individuals. It is essential to diagnose and manage this disease promptly to minimize its impact on patients' quality of life.

References: [1] Combined oxidative phosphorylation defect type 9 is a rare mitochondrial disease due to a defect in mitochondrial protein synthesis. [2] A mitochondrial disease characterized by failure to thrive, poor feeding, hypertrophic cardiomyopathy, hepatomegaly, and psychomotor retardation. Death in ... [7] Definition. A mitochondrial disease characterized by failure to thrive, poor feeding, hypertrophic cardiomyopathy, hepatomegaly, and psychomotor retardation. [9] Definition. A combined oxidative phosphorylation deficiency that has_material_basis_in homozygous or compound heterozygous mutation in the MRPL3 gene on ...

Combined oxidative phosphorylation deficiency 9 (COXPD9) is a rare mitochondrial disease characterized by a range of signs and symptoms.

Initial Normal Growth and Development: In some cases, affected individuals may experience normal growth and development initially, followed by the onset of symptoms [11][12].

Failure to Thrive: One of the primary signs of COXPD9 is failure to thrive, which can manifest as poor feeding, weight loss, and decreased appetite [11][12][13].

Psychomotor Delay: Affected individuals may experience psychomotor delay, which can include delays in achieving motor or mental milestones, such as delayed speech and language development [1][6].

Poor Feeding: Poor feeding is a common symptom of COXPD9, which can lead to failure to thrive and other complications [11][12][13].

Dyspnea: Some individuals with COXPD9 may experience dyspnea (shortness of breath) due to severe hypertrophic cardiomyopathy [11][12][13].

Severe Hypertrophic Cardiomyopathy: This is a serious cardiac condition characterized by thickening of the heart muscle, which can lead to breathing difficulties and other complications [11][12][13].

Hepatomegaly: Enlargement of the liver (hepatomegaly) is another symptom associated with COXPD9 [11][12][13].

It's essential to note that the signs and symptoms of COXPD9 can vary depending on the individual and the specific type of disorder they are afflicted with.

Combined oxidative phosphorylation deficiency 9 (COXPD9) is a rare mitochondrial disease due to a defect in mitochondrial protein synthesis. Diagnostic tests for COXPD9 typically involve a combination of clinical evaluation, laboratory studies, and genetic testing.

Laboratory Studies

• Increased plasma lactate and alanine levels are often observed in patients with COXPD9 (2).
• Abnormal liver enzymes and decreased activity of mitochondrial respiratory chain complexes I, II, III, IV, and V have been reported in affected individuals (5).

Genetic Testing

• Genetic testing can confirm the diagnosis of COXPD9 by identifying pathogenic variants in the genes responsible for mitochondrial protein synthesis.
• Testing can be performed for more than 280 genes, a smaller subset of genes, or even just 1 gene, with an accuracy rate of >95% (10).

Other Diagnostic Tests

• Clinical evaluation and physical examination may reveal signs of neurological impairment, failure to thrive, and other systemic symptoms associated with COXPD9.
• Imaging studies such as MRI or CT scans may be performed to assess the extent of neurological involvement.

It is essential to note that a thorough evaluation of the patient's medical history, physical examination, and genetic testing are necessary for an accurate diagnosis of COXPD9 (6).

Combined Oxidative Phosphorylation Deficiency (COXPD) type 9 is a rare mitochondrial disease characterized by initially normal growth and development followed by the infantile-onset of failure to thrive, psychomotor delay, poor feeding, dyspnea, severe hypertrophic cardiomyopathy, and hepatomegaly.

Current Treatment Options:

While there are no specific treatments available for COXPD type 9, various therapeutic strategies have been explored to manage its symptoms. These include:

• Coenzyme Q10 (CoQ10): This antioxidant has been shown to improve energy production in mitochondria and may help alleviate some symptoms of COXPD.
• Idebenone: A synthetic coenzyme Q10 derivative that has been used to treat mitochondrial diseases, including COXPD. It works by increasing the levels of CoQ10 in the mitochondria.
• Riboflavin (Vitamin B2): This vitamin is essential for energy production and may help alleviate some symptoms of COXPD.

Other Therapeutic Strategies:

In addition to these specific treatments, other therapeutic strategies have been explored to manage the symptoms of COXPD type 9. These include:

• Palliative care: Focusing on providing relief from the symptoms, pain, and stress of a serious illness.
• Nutritional support: Ensuring adequate nutrition is essential for overall health and may help alleviate some symptoms of COXPD.

Important Considerations:

It's essential to note that each individual with COXPD type 9 may respond differently to these treatments. Therefore, it's crucial to work closely with a healthcare provider to develop a personalized treatment plan.

References:

• [12] Combined oxidative phosphorylation defect type 9 is a rare mitochondrial disease due to a defect in mitochondrial protein synthesis characterized by initially normal growth and development followed by the infantile-onset of failure to thrive, psychomotor delay, poor feeding, dyspnea, severe hypertrophic cardiomyopathy and hepatomegaly.
• [13] Combined oxidative phosphorylation deficiency 9 Summary A rare mitochondrial disease due to a defect in mitochondrial protein synthesis characterized by initially normal growth and development followed by the infantile-onset of failure to thrive, psychomotor delay, poor feeding, dyspnea, severe hypertrophic cardiomyopathy and hepatomegaly.
• [4] Therapeutic strategies for mitochondrial diseases include the use of agents enhancing electron transfer chain function (coenzyme Q 10 , idebenone, ribo-flavin, ...).

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-oxidation disorders, such as very-long-chain acyl-CoA dehydrogenase deficiency (VLCAD), and other mitochondrial encephalomyopathies.

In particular, for COXPD9, a rare mitochondrial disease due to a defect in mitochondrial protein synthesis, the differential diagnosis may include:

• Long-chain fatty acid beta-oxidation disorders:
  • Very-long-chain acyl-CoA dehydrogenase deficiency (VLCAD)
  • Carnitine palmitoyltransferase II deficiency
  • Acyl-CoA dehydrogenase long chain 3 deficiency
• Other mitochondrial encephalomyopathies:
  • Mitochondrial myopathies, such as Kearns-Sayre syndrome and MELAS syndrome
  • Neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease

It is essential to note that the diagnosis of COXPD9 requires a comprehensive evaluation of clinical features, laboratory tests, and genetic analysis. A detailed medical history, physical examination, and laboratory investigations, including enzyme assays and genetic testing, are necessary to establish an accurate diagnosis.

The first case of combined oxidative phosphorylation deficiency-1 due to a GFM1 mutation in the Serbian population: a case report and literature review [14] highlights the importance of differential diagnosis in COXPD. The authors emphasize that a thorough evaluation of clinical features and laboratory tests is crucial for establishing an accurate diagnosis and developing effective treatment strategies.

In conclusion, the differential diagnosis of COXPD9 includes long-chain fatty acid beta-oxidation disorders and other mitochondrial encephalomyopathies. A comprehensive evaluation of clinical features, laboratory tests, and genetic analysis is necessary to establish an accurate diagnosis and develop effective treatment strategies.

References:

[12] 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).

[13] FormalPara Respiratory Chain and Oxidative Phosphorylation System . The respiratory chain (complexes I–IV) and oxidative phosphorylation (OXPHOS) system (complexes I–V) are embedded in the inner mitochondrial membrane and are responsible for ATP production by aerobic metabolism ( Fig. 10.1).

[15] Combined oxidative phosphorylation defect type 9 is a rare mitochondrial disease due to a defect in mitochondrial protein synthesis characterized by initially normal growth and development followed by the infantile-onset of failure to thrive, psychomotor delay, poor feeding, dyspnea, severe hypertrophic cardiomyopathy and hepatomegaly.