mitochondrial complex III deficiency nuclear type 3

Mitochondrial complex III deficiency nuclear type 3 (MC3DN3) is a rare genetic disorder that affects the mitochondria, which are the energy-producing structures within cells.

Causes and Symptoms

MC3DN3 is caused by mutations in the MT-CYB gene, which codes for a subunit of mitochondrial complex III. This condition can lead to a highly variable phenotype, depending on which tissues are affected (4, 7). The symptoms of MC3DN3 can include:

• Lactic acidosis
• Hypotonia (low muscle tone)
• Hypoglycemia (low blood sugar)
• Respiratory problems
• Cardiac issues

Prevalence and Inheritance

MC3DN3 is inherited in an autosomal recessive manner, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition. The prevalence of MC3DN3 is not well established, but it is considered to be one of the least common oxidative phosphorylation defects associated with mitochondrial disease (8).

Treatment and Management

There is no specific treatment for MC3DN3, and management typically involves supportive care to alleviate symptoms and prevent complications. This may include nutritional support, respiratory therapy, and cardiac monitoring.

References:

• [4] A disorder of the mitochondrial respiratory chain resulting in a highly variable phenotype depending on which tissues are affected.
• [7] A disorder of the mitochondrial respiratory chain resulting in a highly variable phenotype depending on which tissues are affected.
• [8] by E Fernández-Vizarra · 2015 · Cited by 153 — Complex III (CIII) deficiency is one of the least common oxidative phosphorylation defects associated to mitochondrial disease.

Mitochondrial complex III deficiency, also known as Complex III deficiency, is a rare genetic disorder that affects the mitochondria's ability to produce energy for the body.

Clinical Features

• Abnormal cellular phenotype [1]
• Decreased activity of mitochondrial complex III [1]
• Abnormality of metabolism/homeostasis [1]

People who are mildly affected tend to have:

• Muscle weakness (myopathy) and extreme tiredness (fatigue), particularly during exercise (exercise intolerance) [2][3][5]
• Other associated symptoms include renal tubular disease, skin lesions, diabetes mellitus, proximal muscle weakness, and retinopathy [4]

In severe cases, the disorder can manifest at birth with:

• Lactic acidosis
• Hypotonia
• Hypoglycemia

Additional Symptoms

• Affected individuals may also experience:
  • Failure to thrive
  • Developmental delay or regression
  • Poor eye contact and loss of motor skills with ataxia [9]

It's essential to note that the phenotype is variable, and the severity of symptoms can range from mild to severe.

References:

[1] Context result 1 [2] Context result 2 [3] Context result 3 [4] Context result 4 [5] Context result 5 [6] Context result 6 [7] Context result 7 [8] Context result 8 [9] Context result 9

Mitochondrial complex III deficiency, nuclear type 3 can be diagnosed through various genetic tests.

• Genetic testing: This involves analyzing the DNA to identify mutations in one or more genes associated with mitochondrial disorders. The test is typically performed on a sample of whole blood or DNA (Context [3], [4]).
• Family-based testing: In some cases, family-based testing may be recommended, which includes testing for the patient and their relatives (Context [3], [4]).
• Clinical genetic tests: These tests are available from various laboratories and can be ordered by a healthcare provider. The specific test used may depend on the clinical indication and the laboratory's capabilities (Context [6], [7]).

It is essential to note that mitochondrial complex III deficiency, nuclear type 3 is an autosomal recessive disorder, meaning that both parents are typically carriers of the mutated gene, and each child has a 25% chance of inheriting two copies of the mutated gene, one from each parent (Context [8]).

Mitochondrial complex III deficiency is a genetic condition that can affect various tissues, including the brain, kidneys, liver, heart, and skeletal muscles [3]. As for drug treatment, there are limited options available.

According to existing research, patients with primary mitochondrial disorders should be offered CoQ10 in its reduced form (ubiquinol) as part of their treatment plan [4]. However, it's essential to note that the effectiveness of this treatment can vary depending on the individual case and the severity of the condition.

Another drug that has been studied for its potential benefits in treating mitochondrial disorders is bezafibrate. This fibrate medication increases mitochondrial biogenesis and was originally licensed to treat hyperlipidaemia [5]. However, it's crucial to consult with a medical professional before considering any treatment options.

It's also worth noting that clinicians often use antioxidants, vitamins, and auxiliary factors as mainstay treatments for patients with mitochondrial diseases, including arginine, which may have some benefits in treating complex III deficiency [7].

Complex III (CIII) deficiency is one of the least common oxidative phosphorylation defects associated with mitochondrial disease, and treatment options are limited. Further research is needed to develop more effective treatments for this condition.

References: [3] - Mitochondrial complex III deficiency is a genetic condition that can affect various tissues. [4] - Patients with primary mitochondrial disorders should be offered CoQ10 in its reduced form (ubiquinol) as part of their treatment plan. [5] - Bezafibrate increases mitochondrial biogenesis and was originally licensed to treat hyperlipidaemia. [7] - Clinicians often use antioxidants, vitamins, and auxiliary factors as mainstay treatments for patients with mitochondrial diseases.

Mitochondrial complex III deficiency, nuclear type 3 (MCIIIID NT3) is a severe multisystem disorder characterized by impaired mitochondrial function and energy production. When diagnosing MCIIIID NT3, it's essential to consider differential diagnoses that can mimic or co-occur with this condition.

Differential Diagnoses:

• Fatty acid oxidation defects (FAODs): These disorders affect the breakdown of fatty acids for energy production, leading to similar symptoms like hypoglycemia and hyperlactatemia [4].
• Glycogen storage diseases (GSDs): GSDs are a group of inherited disorders that affect glycogen metabolism, which can also present with hypoglycemia and lactic acidosis [4].
• Mitochondrial oxidative phosphorylation defects: These conditions involve impaired energy production in the mitochondria, leading to symptoms like hypoglycemia, hyperlactatemia, and encephalopathy [5].

Key Considerations:

When differentiating MCIIIID NT3 from these conditions, it's crucial to consider the following factors:

• Clinical presentation: The severity and progression of symptoms can help distinguish between these disorders.
• Laboratory findings: Specific biochemical markers, such as lactate levels and fatty acid profiles, can aid in diagnosis.
• Genetic testing: Molecular genetic analysis can confirm the presence of mutations in the UQCRB gene or other relevant genes.

References:

[4] Mori et al. (2015) - Ophthalmologic and audiologic exams were normal. Differential diagnoses included fatty acid oxidation defects, GSDs, and mitochondrial oxidative phosphorylation defects [4].

[5] Yekedüz et al. (2022) - The most important findings of the mitochondrial complex III deficiency, nuclear type 3 are hypoglycemia and hyperlactatemia [5].