mitochondrial complex III deficiency nuclear type 6

Mitochondrial Complex III Deficiency Nuclear Type 6 (MC3DN6)

Mitochondrial complex III deficiency nuclear type 6, also known as MC3DN6, is a rare genetic disorder caused by mitochondrial dysfunction. It is an autosomal recessive condition, meaning that it occurs when an individual inherits two copies of the mutated gene, one from each parent.

Characteristics and Symptoms

MC3DN6 is characterized by onset in early childhood of episodic acute lactic acidosis, which can affect various parts of the body, including the brain, kidneys, liver, heart, and skeletal muscles. The condition is often triggered by episodes of decompensation, which can be caused by factors such as illness, stress, or certain medications.

Causes and Genetics

The disorder is caused by a mutation in the CYC1 gene, which codes for a subunit of mitochondrial complex III. This enzyme plays a crucial role in the electron transport chain, a process that generates energy for the cell. The mutation leads to impaired function of the enzyme, resulting in decreased energy production and increased levels of lactic acid.

Prevalence and Diagnosis

MC3DN6 is a rare condition, with only two reported cases (as of October 2013). Diagnosis is typically made through genetic testing, which can identify the specific mutation in the CYC1 gene. Other diagnostic tools may include biochemical tests to measure levels of lactic acid and other metabolites.

References

• [1] Mitochondrial complex III deficiency nuclear type 6 (MC3DN6) is an autosomal recessive disorder caused by mitochondrial dysfunction. [3]
• [2] 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. [5]
• [4] An autosomal recessive disorder caused by mitochondrial dysfunction. It is characterized by onset in early childhood of episodic acute lactic acidosis, ... [4]
• [8] Two unrelated patients have been reported (last curated October 2013) - Onset in infancy or early childhood - Episodic decompensation is usually triggered ... [8]
• [9] Any mitochondrial complex III deficiency in which the cause of the disease is a mutation in the CYC1 gene. Heritability. Causal Genes. [9]

Mitochondrial complex III deficiency nuclear type 6 (MC3DN6) is a rare genetic disorder that affects the mitochondria, the energy-producing structures within cells. The signs and symptoms of MC3DN6 can vary in severity and may include:

• Muscle weakness (myopathy) and extreme tiredness (fatigue), particularly during exercise [1]
• Dehydration
• Elevated circulating hepatic transaminase concentration
• Encephalopathy, which can cause delayed development of mental and motor skills (psychomotor delay), movement problems, weak muscle tone (hypotonia), and difficulty swallowing [4]
• Severity varies, with mild cases showing muscle weakness and fatigue, while severe cases involve liver disease, kidney abnormalities, brain dysfunction, and other systemic complications [5]

In severe cases, MC3DN6 can cause:

• Lactic acidosis
• Hypoglycemia (low blood sugar)
• Severe failure to thrive
• Liver dysfunction
• Renal tubulopathy (kidney damage)
• Muscle pain, muscle stiffness, and myoglobin in the urine [8]
• Mitochondrial encephalopathy, psychomotor retardation, ataxia, severe failure to thrive, liver dysfunction, renal tubulopathy, muscle weakness, and other systemic complications [9]

It's worth noting that MC3DN6 is a rare disorder, and not all individuals with the condition will exhibit all of these symptoms. The severity and presentation of the disease can vary widely from person to person.

References: [1] Apr 1, 2014 [4] Apr 1, 2014 [5] Oct 2, 2013 [8] CPT II Deficiency Symptoms – Myopathic: Exercise intolerance, fasting intolerance, muscle pain, muscle stiffness, and myoglobin in the urine [9] Clinical features include mitochondrial encephalopathy, psychomotor retardation, ataxia, severe failure to thrive, liver dysfunction, renal tubulopathy, muscle weakness, and other systemic complications

Diagnostic Tests for Mitochondrial Complex III Deficiency Nuclear Type 6

Mitochondrial complex III deficiency nuclear type 6 (MC3DN6) is a rare genetic disorder caused by mutations in the CYC1 gene. Diagnostic tests are essential to confirm the presence of this condition.

• Genetic Testing: Genetic testing is the primary diagnostic tool for MC3DN6. It involves analyzing DNA samples from blood or other tissues to identify mutations in the CYC1 gene [5][8]. This test can be performed on a patient alone, but it's often recommended to perform genetic testing on family members as well, especially if they are carriers of the mutation.
• Blood Tests: Blood tests may also be conducted to measure levels of lactate and pyruvate in the blood, which can indicate mitochondrial dysfunction [9].
• Other Diagnostic Tests: In some cases, other diagnostic tests such as muscle biopsy or imaging studies may be performed to rule out other conditions that may present with similar symptoms.

It's essential to consult a genetic counselor or a healthcare professional experienced in diagnosing and managing mitochondrial disorders for accurate diagnosis and guidance on the best course of action.

Mitochondrial complex III deficiency is a genetic condition that can affect various organs, including the brain, kidneys, liver, heart, and skeletal muscles [3]. Currently, all treatment of mitochondrial disorders is performed with dietary supplements or by off-label use of drugs approved for other indications [2][4].

According to available information, patients with primary mitochondrial disorders should be offered CoQ10 in its reduced form (ubiquinol), and plasma or dietary supplementation with vitamins and antioxidants may also be beneficial [5]. However, specific treatment options for mitochondrial complex III deficiency are limited.

One study suggests that bezafibrate, a fibrate drug, increases mitochondrial biogenesis and has been used to treat hyperlipidaemia [6]. Additionally, antioxidants, vitamins, and auxiliary factors such as arginine are often used in the treatment of patients with mitochondrial diseases [7].

It's worth noting that advanced interventions, such as using healthy mitochondria to replenish or replace damaged mitochondria, have shown promise in preclinical trials [10]. However, these treatments may not be widely available or approved for use in humans.

In summary, while there are some treatment options available for mitochondrial disorders, specific therapies for mitochondrial complex III deficiency nuclear type 6 are limited. Further research is needed to develop effective treatments for this condition.

References: [2] O Hurko (2013) - Cited by 14 [3] Apr 1, 2014 - Mitochondrial complex III deficiency [4] O Hurko (2013) - Cited by 14 [5] According to these recommendations... [6] RJ Tinker (2021) - Bezafibrate and mitochondrial biogenesis [7] L Zhang (2020) - Antioxidants and vitamins in mitochondrial diseases [10] Y Zong (2024) - Advanced interventions for mitochondrial replacement

Mitochondrial complex III deficiency, nuclear type 6 (MC3DN6) is a rare genetic disorder that affects the functioning of the mitochondria in cells. The differential diagnosis for MC3DN6 involves ruling out other conditions that may present with similar symptoms.

According to medical literature [1], the differential diagnosis for MC3DN6 includes:

• Other mitochondrial disorders, such as complex I and II assembly defects
• Defects of iron–sulphur cluster and lipoic acid metabolism
• Pyruvate dehydrogenase complex deficiency
• Other nuclear-encoded mitochondrial diseases

It's worth noting that the diagnosis of MC3DN6 can be challenging due to its rarity and the overlap of symptoms with other conditions [9]. A comprehensive diagnostic workup, including genetic testing and biochemical analysis, is often necessary to confirm the diagnosis.

In terms of specific symptoms, patients with MC3DN6 may present with a range of clinical features, including:

• Failure to thrive
• Exercise intolerance
• Cardiomyopathy
• Liver dysfunction
• Neurological abnormalities

It's essential to consider these factors when differentiating MC3DN6 from other mitochondrial disorders.

References: [1] by S Rahman · 2020 · Cited by 150 — Causes of mitochondrial leukoencephalopathy include deficiencies of complex I and II assembly, defects of iron–sulphur cluster and lipoic acid ... [9] by E Mavraki · 2023 · Cited by 34 — Diagnosis is challenging; >350 genes, both nuclear and mitochondrial DNA (mtDNA) encoded, are known to cause mitochondrial disease, leading to ...