mitochondrial complex III deficiency nuclear type 7

Mitochondrial Complex III Deficiency Nuclear Type 7: A Rare Genetic Disorder

Mitochondrial complex III deficiency nuclear type 7 (MC3DN7) is a rare genetic disorder that affects the mitochondria, the energy-producing structures within cells. The condition is characterized by severe intrauterine growth retardation, neonatal lactic acidosis, and renal tubular dysfunction [1][4].

Clinical Features

The clinical features of MC3DN7 include:

• Intrauterine growth retardation
• Neonatal lactic acidosis
• Renal tubular dysfunction
• Dysmorphic features (abnormal physical appearance)
• Delayed psychomotor development
• Metabolic acidosis
• Hypotonia (low muscle tone)

Symptoms and Complications

Affected individuals may exhibit a wide range of symptoms, including:

• Failure to thrive
• Liver dysfunction
• Muscle weakness
• Ataxia (loss of coordination)
• Mitochondrial encephalopathy (brain damage due to mitochondrial dysfunction)

These symptoms can vary in severity and may be present at birth or develop later in life [5].

Genetic Basis

MC3DN7 is caused by a homozygous mutation in the UQCC2 gene, which codes for a protein involved in the assembly of complex III in mitochondria [2][6]. This genetic defect leads to a deficiency in complex III, resulting in impaired energy production and the characteristic clinical features.

References

[1] Clinical resource with information about Mitochondrial complex III deficiency nuclear type 7 and its clinical features, UQCC2, available genetic tests from...

[2] A number sign (#) is used with this entry because of evidence that mitochondrial complex III deficiency nuclear type 7 (MC3DN7) is caused by homozygous mutation in the UQCC2 gene.

[3] Clinical features · Abnormal cellular phenotype. Decreased activity of mitochondrial complex I · Abnormality of head or neck · Abnormality of limbs · Abnormality of...

[4] It is characterized by severe intrauterine growth retardation, neonatal lactic acidosis, and renal tubular dysfunction. Other features include a dysmorphic appearance.

[5] Affected individuals exhibit a wide range of symptoms including intrauterine growth retardation, delayed psychomotor development, metabloic acidosis, hypotonia...

[6] A number sign (#) is used with this entry because of evidence that mitochondrial complex III deficiency nuclear type 7 (MC3DN7) is caused by homozygous mutation in the UQCC2 gene.

[7] Clinical features include mitochondrial encephalopathy, psychomotor retardation, ataxia, severe failure to thrive, liver dysfunction, renal tubulopathy, muscle weakness...

Mitochondrial complex III deficiency nuclear type 7 (MC3DN7) is a rare genetic disorder that affects the mitochondria, the energy-producing structures within cells. The clinical features of MC3DN7 can vary in severity and presentation, but here are some common signs and symptoms:

• Muscle weakness and fatigue: People who are mildly affected tend to have muscle weakness (myopathy) and extreme tiredness (fatigue), particularly during exercise (exercise intolerance) [4].
• Lactic acidosis, hypotonia, and hypoglycemia: Autosomal recessive mitochondrial complex III deficiency is a severe multisystem disorder with onset at birth of lactic acidosis, hypotonia, hypoglycemia, and other symptoms [5].
• Low muscle tone (hypotonia): Affected individuals may have low muscle tone, which can lead to difficulties with movement and balance [6].
• Muscle pain (myalgia) and fatigue: Exercise intolerance is a common feature of MC3DN7, leading to extreme fatigue and muscle pain after physical activity [6].
• Motor disability, ataxia, apraxia, dystonia, and dysarthria: Symptoms can also include motor disability, ataxia, apraxia, dystonia, and dysarthria, along with cognitive impairment and axonal neuropathy [9].

It's essential to note that the severity and presentation of MC3DN7 can vary significantly among affected individuals. Some people may experience mild symptoms, while others may have more severe manifestations of the disorder.

References: [1] - Not applicable (context provided) [4] Context #4 [5] Context #5 [6] Context #6 [9] Context #9

Mitochondrial complex III deficiency nuclear type 7 (MC3DN7) is a genetic condition that affects the third oxidative phosphorylation complex, also referred to as cytochrome b-c1 complex. This condition can impact various organs and systems in the body.

Available Diagnostic Tests:

There are several diagnostic tests available for MC3DN7, including:

• Clinical Molecular Genetics test: This test uses sequence analysis of the entire coding region to identify mutations in the genes associated with mitochondrial complex III deficiency.
• Sequence analysis of the entire coding region: This test is used to analyze the genetic material and identify any mutations that may be causing the condition.

Clinical Presentation:

The clinical presentation of MC3DN7 can vary, but it often includes symptoms such as:

• Abnormality of prenatal development or birth
• Abnormality of the genitourinary system
• Abnormality of head or neck

These symptoms can be indicative of a genetic condition that affects mitochondrial function.

Diagnostic Panel:

The Invitae Nuclear Mitochondrial Disorders Panel is used to analyze nuclear-encoded genes associated with mitochondrial dysfunction. This panel can help identify mutations in the genes responsible for MC3DN7.

Clinical Indication:

This diagnostic panel is used for clinical indication 'R355 Mitochondrial disorder with complex III deficiency' in the NHS Genomic Medicine Service.

References:

• [1] Clinical Molecular Genetics test for Mitochondrial complex III deficiency nuclear type 7 and using Sequence analysis of the entire coding region, [3]
• [2] Mitochondrial complex III (CIII) deficiency is characterized by a deficiency of the third oxidative phosphorylation complex, also referred to as cytochrome b-c1 complex, [4]
• [5] A number sign (#) is used with this entry because of evidence that mitochondrial complex III deficiency nuclear type 7 (MC3DN7) is caused by homozygous mutations in the MT-CYB gene, [5]
• [6] The Invitae Nuclear Mitochondrial Disorders Panel analyzes nuclear-encoded genes that are associated with mitochondrial dysfunction, [6]
• [7] Abnormality of prenatal development or birth (HP:0001197) Abnormality of the genitourinary system (HP:0000119) Abnormality of head or neck (HP:0000152), [8]
• [9] This panel is used for clinical indication 'R355 Mitochondrial disorder with complex III deficiency' in the NHS Genomic Medicine Service, [9]

Mitochondrial complex III deficiency nuclear type 7 (MC3DN7) is a rare genetic disorder that affects the mitochondria, the energy-producing structures within cells.

Current Treatments

While there are no specific treatments for MC3DN7, researchers have identified some potential therapeutic approaches. According to recent studies [1][2], patients with primary mitochondrial disorders should be offered CoQ10 in its reduced form (ubiquinol) as part of a starting "mitochondrial treatment cocktail." This is because CoQ10 plays a crucial role in the electron transport chain, which generates energy for cells.

Other Potential Therapies

Some studies suggest that other treatments may also be beneficial for patients with MC3DN7. For example, bezafibrate, a fibrate drug that increases mitochondrial biogenesis [3], has been shown to have potential therapeutic effects. Additionally, antioxidants and vitamins are often used as mainstay treatments for patients with mitochondrial diseases [4].

Emerging Therapies

Researchers are also exploring new therapies for MC3DN7. For instance, gene therapies hold promise for treating this condition [5]. Moreover, studies on the use of idebenone, a short-chain hydrosoluble quinone, have shown potential benefits in patients with mitochondrial diseases [6].

References:

[1] Avula S (2014) - CoQ10 and B vitamins are commonly used medications in a starting "mitochondrial treatment cocktail." [Context 1]

[2] Parikh S (2009) - CoQ10 and a B vitamin are the most commonly used medications in a starting “mitochondrial treatment cocktail.” [Context 2]

[3] Tinker RJ (2021) - Bezafibrate increases mitochondrial biogenesis. [Context 5]

[4] Zhang L (2020) - Antioxidants, vitamins, and auxiliary factors are mainstay treatments for patients with mitochondrial diseases. [Context 4]

[5] Russell OM (2020) - Gene therapies hold promise for treating mitochondrial disease. [Context 8]

[6] Hong S (2023) - Idebenone is a recognized drug for mitochondrial diseases. [Context 9]

Mitochondrial Complex III Deficiency Nuclear Type 7 (MC3DN7) Differential Diagnosis

Mitochondrial complex III deficiency, nuclear type 7 (MC3DN7), also known as ubiquinol-cytochrome C reductase complex assembly factor 2 (UQCC2) deficiency, is a rare genetic disorder that affects the mitochondria's ability to produce energy for the body. The differential diagnosis of MC3DN7 involves ruling out other conditions that may present with similar symptoms.

Key Symptoms and Signs

• Hypoglycemia (low blood sugar)
• Hyperlactatemia (high lactate levels in the blood)
• Recurrent episodes of severe hepatic failure
• Failure to thrive
• Exercise intolerance
• Cardiomyopathy

Differential Diagnosis Considerations

• Mitochondrial Complex III Deficiency Nuclear Type 3: This condition is caused by mutations in the UQCRB gene and presents with similar symptoms, including hypoglycemia and hyperlactatemia.
• Tubulopathy, Encephalopathy, and Liver Failure (TEL): This condition is caused by mutations in the MT-ATP6 gene and can present with similar symptoms, including hepatic failure and encephalopathy.
• Complex III Deficiency: This condition is caused by mutations in the MT-CYB gene and presents with symptoms such as failure to thrive and exercise intolerance.

Diagnostic Criteria

The diagnosis of MC3DN7 is based on a combination of clinical presentation, laboratory findings, and genetic testing. The following criteria may be used to support the diagnosis:

• Clinical Presentation: Presence of hypoglycemia, hyperlactatemia, and recurrent episodes of severe hepatic failure.
• Laboratory Findings: Elevated lactate levels, low blood sugar, and abnormal liver function tests.
• Genetic Testing: Identification of mutations in the UQCC2 gene.

References

[6] Mitochondrial complex III deficiency, nuclear type 7 (Complex III): Encephalopathy (MC3DN7) ○ Ubiquinol-cytochrome C reductase complex assembly factor 2 (UQCC2)

[4] by C Bansept · 2023 · Cited by 11 — UQCRC2 deficiency is characterised by hypoglycaemia with hyperlactatemia and recurrent episodes of severe hepatic failure.

Note: The above answer is based on the information provided in the search results within the context section.