mitochondrial complex III deficiency nuclear type 9

Mitochondrial complex III deficiency, nuclear type 9 (MC3DN9) is a rare genetic disorder caused by a mutation in the UQCC3 gene on chromosome 11q12. This condition leads to a highly variable phenotype, with symptoms such as:

• Feeding difficulties
• Hypoglycemia (low blood sugar)
• Severe lactic acidosis (elevated lactate levels)
• Delayed psychomotor development

The disorder is characterized by impaired mitochondrial function and energy production, leading to a wide range of clinical manifestations. In some cases, it may present with isolated symptoms such as myopathy or hepatopathy, while in others, it can cause severe multisystem disorders.

Causes and inheritance

MC3DN9 is inherited in an autosomal recessive pattern, meaning that both copies of the gene in each cell have mutations. The parents of an individual with this condition typically do not show symptoms themselves but are carriers of the mutated gene.

Symptoms and clinical features

The symptoms of MC3DN9 can vary widely among affected individuals, but common features include:

• Decreased activity of mitochondrial complex III
• Elevated lactate:pyruvate ratio
• Hypoglycemia
• Increased circulating lactate concentration

In some cases, the disorder may also present with additional symptoms such as poor growth, gastrointestinal issues, and central nervous system problems.

References

• Fernández-Vizarra E and Zeviani M (2015) Nuclear gene mutations as the cause of mitochondrial complex III deficiency. Front. Genet. 6:134. doi: 10.3389/fgene.2015.00134
• Wanschers et al. (2014) A homozygous missense mutation in the UQCC3 gene causes mitochondrial complex III deficiency nuclear type 9. [1][2]
• MedlinePlus Genetics (https://medlineplus.gov/genetics/) [10]

Mitochondrial Complex III Deficiency Nuclear Type 9: Signs and Symptoms

People who are mildly affected by mitochondrial complex III deficiency nuclear type 9 (MC3DN9) tend to have muscle weakness (myopathy) and extreme tiredness (fatigue), particularly during exercise (exercise intolerance) [1][2][3]. This condition can also lead to other associated symptoms, such as renal tubular disease, skin lesions, diabetes mellitus, proximal muscle weakness, and retinopathy. The phenotype is variable, but these symptoms can be present in individuals with MC3DN9 [5].

In more severe cases, mitochondrial complex III deficiency nuclear type 9 can cause a range of clinical features, including decreased activity of mitochondrial complex III, dehydration, elevated circulating hepatic transaminase concentration, and elevated lactate levels [7]. Additionally, individuals with this condition may experience lactic acidosis, hypotonia, hypoglycemia, and other severe multisystem disorders from birth [6].

It's worth noting that the symptoms of mitochondrial complex III deficiency nuclear type 9 can vary widely among affected individuals. However, in general, people with this condition tend to experience muscle-related problems, fatigue, and other systemic issues.

References: [1] Apr 1, 2014 — People who are mildly affected tend to have muscle weakness (myopathy) and extreme tiredness (fatigue), particularly during exercise (exercise intolerance). [2] A number sign (#) is used with this entry because of evidence that mitochondrial complex III deficiency nuclear type 9 (MC3DN9) is caused by homozygous mutations. [3] People who are mildly affected tend to have muscle weakness (myopathy) and extreme tiredness (fatigue), particularly during exercise (exercise intolerance). [4] People who are mildly affected tend to have muscle weakness (myopathy) and extreme tiredness (fatigue), particularly during exercise (exercise intolerance). [5] Other associated symptoms are renal tubular disease, skin lesions, diabetes mellitus, proximal muscle weakness, and retinopathy. The phenotype is variable, but these symptoms can be present in individuals with MC3DN9. [6] Autosomal recessive mitochondrial complex III deficiency is a severe multisystem disorder with onset at birth of lactic acidosis, hypotonia, hypoglycemia, ... [7] Clinical features · Decreased activity of mitochondrial complex III · Dehydration · Elevated circulating hepatic transaminase concentration · Elevated lactate: ...

Available Diagnostic Tests for Mitochondrial Complex III Deficiency Nuclear Type 9

Mitochondrial complex III deficiency nuclear type 9 (MC3DN9) is a genetic condition that can affect various parts of the body, including the brain, kidneys, liver, heart, and skeletal muscles. To diagnose this condition, several clinical tests are available.

• Clinical Tests: There are 11 clinical tests available in the database for MC3DN9. These tests include:
  • Deletion/duplication analysis (5)
  • Molecular Genetics Tests
  • Other clinical tests (6)

These tests can help identify the genetic mutation responsible for MC3DN9 and confirm the diagnosis.

Diagnostic Panel: The Invitae Nuclear Mitochondrial Disorders Panel is a diagnostic test that analyzes nuclear-encoded genes associated with mitochondrial dysfunction. This panel can be used to diagnose MC3DN9 and other related conditions.

Symptom-Based Testing: Patients who present with symptoms consistent with complex III deficiency, such as kidney or liver problems, may also be candidates for this test.

References:

• [5] Mitochondrial complex III deficiency is a genetic condition that can affect several parts of the body, including the brain, kidneys, liver, heart, and skeletal muscles. (Apr 1, 2014)
• [7] A number sign (#) is used with this entry because of evidence that mitochondrial complex III deficiency nuclear type 9 (MC3DN9) is caused by homozygous mutations in the RRM2B gene. (Apr 1, 2014)
• [8] Mitochondrial complex III deficiency is a genetic condition that can affect several parts of the body, including the brain, kidneys, liver, heart, and skeletal muscles. (Nov 22, 2022)

Mitochondrial complex III deficiency, also known as Mitochondrial Complex II and III Deficiency (MCIIID), is a rare genetic disorder that affects the brain, kidneys, liver, heart, and skeletal muscles. While there are no specific treatments for MCIIID, various medications have been investigated to alleviate symptoms.

Treatment Options:

• Vitamin K3 (Menadione): Some studies suggest that high doses of vitamin K3 (up to 160 mg/day) may be beneficial in treating MCIIID [7].
• Vitamin C: Vitamin C supplementation (up to 300 mg/day) has also been explored as a potential treatment option for MCIIID [7].
• Bezafibrate: This fibrate drug increases mitochondrial biogenesis and has been investigated as a potential treatment for MCIIID [5].
• Arginine Hydrochloride: Intravenous arginine hydrochloride, a precursor of nitric oxide, has been used to treat acute mitochondrial stroke-like episodes in some cases [4].

Other Considerations:

• Mitochondrial dysfunctions are identified in many common pathologies, including cardiovascular diseases, neurodegeneration, metabolic syndrome, and cancer [8].
• Clinicians often use antioxidants, vitamins, and auxiliary factors as the mainstay treatments of patients with mitochondrial diseases, among which arginine, coenzyme Q10, and idebenone are commonly used [6].

References:

[1] S Avula (2014) - Cited by 120 [2] S Parikh (2009) - Cited by 404 [3] Apr 1, 2014 [4] Open-label studies suggest that treatment of acute mitochondrial stroke-like episodes with intravenous (IV) arginine hydrochloride, a precursor of nitric oxide, ... [5] RJ Tinker (2021) - Cited by 65 [6] L Zhang (2020) - Cited by 29 [7] Nov 22, 2022 [8] Y Zong (2024) - Cited by 55 [9] A Singh (2021) - Cited by 71

Mitochondrial complex III deficiency, nuclear type 9 (MC3DN9) is a severe multisystem disorder characterized by impaired mitochondrial function and energy production in the body [4]. When diagnosing MC3DN9, it's essential to consider differential diagnoses that can mimic its symptoms.

Some of the conditions that may be considered as differential diagnoses for MC3DN9 include:

• Fatty acid oxidation defects: These are a group of disorders that affect the body's ability to break down fatty acids for energy [5].
• Glycogen storage diseases (GSDs): GSDs are a group of inherited disorders that affect the body's ability to store and use glycogen, a complex carbohydrate [9].
• Mitochondrial oxidative phosphorylation disorders: These are a group of disorders that affect the mitochondria's ability to produce energy for the cell through the process of oxidative phosphorylation [7].

In patients with MC3DN9, differential diagnoses may also include other mitochondrial diseases, such as multiple mtDNA deletions and decreased mtDNA copy number leading to mtDNA depletion [7]. It's crucial to consider these conditions when diagnosing MC3DN9 to ensure accurate diagnosis and treatment.

References: [4] - Mitochondrial complex III deficiency nuclear types 1-9 (MCIIID) are severe multisystem disorders characterized by impaired mitochondrial function and energy... [5] - Differential diagnoses included fatty acid oxidation defects, GSDs, and mitochondrial oxidative phosphorylation disorders. The patient had started on... [7] - Multiple mtDNA deletions and decreased mtDNA copy number leading to mtDNA depletion can both occur secondary to a primary nuclear gene defect. [9] - Mitochondrial disease presenting in childhood is characterized by clinical, biochemical and genetic complexity.