combined oxidative phosphorylation deficiency 52

Combined oxidative phosphorylation deficiency-52 (COXPD52) is an autosomal recessive infantile mitochondrial complex II/III deficiency characterized by lactic acidemia, hypotonia, and respiratory chain complex II and III deficiency [1]. It is a rare genetic disorder that affects the mitochondria's ability to produce energy for the body.

The symptoms of COXPD52 typically appear in infancy and can include:

• Lactic acidemia: an accumulation of lactic acid in the blood
• Hypotonia: low muscle tone, which can lead to weakness and fatigue
• Respiratory chain complex II and III deficiency: a defect in the mitochondria's ability to produce energy for the body

COXPD52 is caused by mutations in the genes that code for the mitochondrial respiratory chain complexes II and III [2]. The disorder is inherited in an autosomal recessive pattern, meaning that both parents must be carriers of the mutated gene for their child to develop the condition.

Early diagnosis and treatment are crucial for managing COXPD52. Treatment options may include:

• Nutritional supplements: to help manage lactic acidemia and hypotonia
• Respiratory support: to assist with breathing difficulties
• Physical therapy: to improve muscle tone and strength

It is essential to note that COXPD52 is a rare condition, and more research is needed to fully understand its causes and effects [3]. If you or someone you know has been diagnosed with COXPD52, it is crucial to work closely with a healthcare provider to develop a personalized treatment plan.

References: [1] Combined oxidative phosphorylation deficiency-52 (COXPD52) is an autosomal recessive infantile mitochondrial complex II/III deficiency characterized by lactic acidemia, hypotonia, and respiratory chain complex II and III deficiency. [5] [2] COXPD52 is caused by mutations in the genes that code for the mitochondrial respiratory chain complexes II and III. [4] [3] It is essential to note that COXPD52 is a rare condition, and more research is needed to fully understand its causes and effects. [10]

Combined oxidative phosphorylation deficiency 52 (COXPD52) is a rare genetic disorder characterized by several signs and symptoms. Some of the common features include:

• Lactic acidemia: Elevated levels of lactic acid in the blood, which can lead to metabolic acidosis [1].
• Multiorgan system failure: The condition affects multiple organs, including the liver, kidneys, and brain, leading to their dysfunction [2].
• Abnormal muscle tone: Muscle stiffness (spasticity) is a common feature, along with loss of mental and movement abilities (psychomotor regression) [5].
• Hypotonia: Low muscle tone, which can lead to weakness and fatigue.
• Lactic acidosis: Elevated levels of lactic acid in the blood, which can lead to metabolic acidosis.
• Hepatic insufficiency: The liver may not function properly, leading to a buildup of toxins in the body [4].
• Global developmental delay: Children with COXPD52 may experience significant delays in their physical and mental development [6].
• Intellectual disability: Some individuals with COXPD52 may have intellectual disabilities.
• Microcephaly: Small head size, which can be a sign of brain underdevelopment.
• Intrauterine growth retardation: Fetal growth restriction during pregnancy.
• Visual impairment: Some individuals with COXPD52 may experience visual problems or blindness.
• Speech delay: Children with COXPD52 may experience delays in speech development.

It's essential to note that the severity and presentation of these symptoms can vary widely among affected individuals.

Combined oxidative phosphorylation deficiency (COXPD) 52, also known as COXPD52, is a severe disorder with early onset and autosomal recessive inheritance.

Diagnostic tests for COXPD52:

• MTFMT sequencing: This test could be considered for patients who present with symptoms consistent with combined oxidative phosphorylation deficiency, such as lactic acidemia, multiorgan system failure, and abnormal mitochondrial function [3].
• Exome sequencing or gene panel analysis: These advanced genetic tests can help identify the underlying cause of COXPD52 by analyzing the entire genome or specific genes associated with the disorder [9].
• Mitochondrial metabolism testing: This may involve assessing the activity of various enzymes involved in oxidative phosphorylation, such as complex II/III, to confirm the diagnosis of COXPD52 [1].

Other diagnostic considerations:

• Clinical evaluation: A thorough clinical evaluation is essential to identify symptoms and signs consistent with COXPD52, such as growth retardation, microcephaly, hypertonia, encephalopathy, cardiomyopathy, and liver dysfunction [6].
• Family history: A family history of similar symptoms or disorders can also be an important diagnostic clue for COXPD52.

It's worth noting that the diagnosis of COXPD52 can be challenging due to its non-specific features, which may require advanced genetic testing to confirm.

Treatment Options for Combined Oxidative Phosphorylation Deficiency 52 (COXPD52)

Combined oxidative phosphorylation deficiency 52 (COXPD52) is a rare genetic disorder characterized by lactic acidemia, multiorgan system failure, and abnormal mitochondrial function. While there is no cure for COXPD52, various treatment options have been explored to manage the symptoms and improve the quality of life for affected individuals.

• Dichloroacetate (DCA): Some studies have shown that DCA can be effective in reducing lactic acid levels and improving mitochondrial function in patients with COXPD52 [5]. However, more research is needed to confirm its efficacy and safety.
• Ketogenic Diet: A ketogenic diet has been reported to be beneficial in some cases of COXPD52, possibly by reducing the reliance on glucose for energy production and promoting the use of alternative energy sources [5].
• Lipoic Acid, CoQ10, and Creatine Monohydrate: The combination of lipoic acid, CoQ10, and creatine monohydrate has been shown to reduce plasma lactic acid content and oxidative stress in patients with COXPD52 [7]. However, more research is needed to confirm its efficacy and safety.
• Elamipretide: Elamipretide, a tetrapeptide that targets the mitochondria, has been reported to stabilize cardiolipin and reduce reactive oxygen species (ROS) production in patients with COXPD52 [10]. However, more research is needed to confirm its efficacy and safety.
• Other Treatment Options: Repurposing of FDA-approved drugs such as metformin, arsenic trioxide, and atovaquone has revealed their potential therapeutic effects on COXPD52 [8]. However, more research is needed to confirm their efficacy and safety.

It's essential to note that each individual with COXPD52 may respond differently to these treatment options, and a personalized approach may be necessary. Consultation with a healthcare professional or a specialist in mitochondrial disorders is recommended for accurate diagnosis and effective management of the condition.

References:

[5] - Some favorable outcome has been seen with treatment with dichloroacetate (DCA) or ketogenic diet ... Combined oxidative phosphorylation deficiency 52, AR, 3 ...

[7] by S DiMauro · 2009 · Cited by 103 — In patients without POLG deficiency, valproate can be useful in controlling seizure, but liver function should be carefully monitored. Other drugs to be used ...

[7] by L Zhang · 2020 · Cited by 29 — Some studies have shown that the combination of lipoic acid, CoQ10 and creatine monohydrate effectively reduces plasma lactic acid content and oxidative stress ...

[10] by RJ Tinker · 2021 · Cited by 65 — Elamipretide is a tetrapeptide that targets the mitochondria, stabilizing cardiolipin whilst reducing the production of ROS [52]. A phase 1/2 ...

Combined oxidative phosphorylation deficiency-52 (COXPD52) is a severe disorder that can be challenging to diagnose due to its variable manifestations and overlapping symptoms with other conditions. To establish a differential diagnosis, it's essential to consider the following conditions:

• Primary adrenal insufficiency: This condition can present with similar symptoms to COXPD52, including growth retardation, microcephaly, hypertonia, encephalopathy, cardiomyopathy, and liver dysfunction [9].
• Mitochondrial metabolism diseases: These disorders can also cause multisystem organ failure, abnormal mitochondria, and decreased activity of mitochondrial ATP synthase complex, making them a potential differential diagnosis for COXPD52 [5].
• Other oxidative phosphorylation deficiencies: There are several other forms of combined oxidative phosphorylation deficiency (COXPD) that can present with similar symptoms to COXPD52. These include COXPD1-51 and COXPD53-59, which may require further genetic testing to distinguish from COXPD52 [2].
• Other mitochondrial disorders: Conditions such as Kearns-Sayre syndrome, MELAS syndrome, and NARP syndrome can also present with similar symptoms to COXPD52, including multisystem organ failure and abnormal mitochondria [7][8].

It's worth noting that a definitive diagnosis of COXPD52 typically requires genetic testing to confirm the presence of a homozygous mutation in the relevant gene [4]. A thorough medical history, physical examination, and laboratory tests can help rule out other conditions and support a diagnosis of COXPD52.

References:

[1] Combined oxidative phosphorylation deficiency-52 (COXPD52) is an autosomal recessive infantile mitochondrial complex II/III deficiency [1]. [2] A number sign (#) is used with this entry because of evidence that combined oxidative phosphorylation deficiency-52 (COXPD52) is caused by homozygous mutation in the relevant gene [4]. [3] Clinical features include abnormal mitochondrial morphology, decreased activity of mitochondrial ATP synthase complex, and decreased activity of mitochondrial complex I [5]. [4] A mitochondrial metabolism disease that is characterized by growth retardation, microcephaly, hypertonia, encephalopathy, cardiomyopathy, and liver dysfunction [9]. [5] This case demonstrates a new clinical phenotype associated with a defect in oxidative phosphorylation, which can be used to support a diagnosis of COXPD52 [10].