mitochondrial complex IV deficiency nuclear type 13

Mitochondrial complex IV deficiency, nuclear type 13 (MC4DN13) is a rare and severe metabolic disorder that affects the mitochondria, which are the energy-producing structures within cells.

Characteristics:

• MC4DN13 is an autosomal recessive disorder, meaning that it is inherited in an autosomal recessive pattern, where a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.
• The disorder is characterized by hypertrophic cardiomyopathy, which is a thickening of the heart muscle that can lead to heart failure.
• Other symptoms may include:
  • Hypertrophic cardiomyopathy [1]
  • Left ventricular dysfunction [3]
  • Respiratory distress [3]

Prognosis:

Unfortunately, MC4DN13 is a fatal infantile disorder, meaning that it typically leads to death in the first weeks of life. The disorder progresses rapidly and can be life-threatening due to its severe impact on the heart and other vital organs.

It's worth noting that there are different types of mitochondrial complex IV deficiency, including nuclear type 1 (MC4DN1) and nuclear type 3, which have distinct characteristics and symptoms [4][7]. However, MC4DN13 is a specific subtype with its own unique features.

Muscle Weakness and Poor Muscle Tone

Individuals affected by mitochondrial complex IV deficiency, nuclear type 13, tend to experience muscle weakness (myopathy) and poor muscle tone (hypotonia) [3]. This can be a mild symptom, with no other related health problems [5].

Other Possible Symptoms

In more severe cases, individuals may exhibit additional symptoms such as:

• Low muscle tone (hypotonia)
• Muscle pain (myalgia)
• Extreme fatigue in response to physical activity (exercise intolerance) [4]
• Developmental delay
• Ataxia
• Renal tubulopathy
• Anemia
• Hearing loss
• Cardiomyopathy [6]

Important Note

It's worth noting that the severity and range of symptoms can vary widely among individuals with mitochondrial complex IV deficiency, nuclear type 13. Some people may experience only mild symptoms, while others may have more severe manifestations.

References: [3] - People who are mildly affected tend to have muscle weakness (myopathy) and poor muscle tone (hypotonia) with no other related health problems. [4] - Affected individuals may have low muscle tone (hypotonia), muscle pain (myalgia), and extreme fatigue in response to physical activity (exercise intolerance). [5] - People who are mildly affected tend to have muscle weakness (myopathy) and poor muscle tone (hypotonia) with no other related health problems. [6] - Symptoms include hypotonia, failure to thrive, developmental delay, ataxia, renal tubulopathy, anemia, hearing loss, and cardiomyopathy.

Diagnostic Tests for Mitochondrial Complex IV Deficiency, Nuclear Type 13

Mitochondrial complex IV deficiency, nuclear type 13 (MC4DN13) is a genetic disorder that affects the mitochondria's ability to produce energy. Diagnostic tests are essential to confirm this condition.

• Laboratory studies: Increased serum lactate levels are often observed in individuals with MC4DN13 [1][2]. This can be detected through blood tests.
• Genetic testing: Specific genetic tests, such as those related to the COA6 gene, can identify mutations associated with MC4DN13 [2].
• Clinical genetic tests: PreventionGenetics, a laboratory specializing in genetic testing, offers clinical tests for conditions, including mitochondrial complex IV deficiency, nuclear type 1 and 13 [3][4].

These diagnostic tests help confirm the presence of MC4DN13, enabling healthcare professionals to develop an appropriate treatment plan.

References: [1] Mitochondrial complex IV deficiency nuclear type 13 (MC4DN13) ... Laboratory studies show increased serum lactate ... [2] Genetic tests related with Mitochondrial Complex Iv Deficiency, Nuclear Type 13 ; 2, Mitochondrial Complex IV Deficiency via the COA6 Gene ... [3] Clinical Genetic Test offered by PreventionGenetics, part of Exact Sciences for conditions (8): Mitochondrial complex IV deficiency, nuclear type 1; ... [4] ... tests from US and labs around the ... Mitochondrial complex IV deficiency nuclear type 13 (MC4DN13) ... Laboratory studies show increased serum lactate ...

Treatment Options for Mitochondrial Complex IV Deficiency Nuclear Type 13

Mitochondrial complex IV deficiency nuclear type 13 (MC4DN13) is a rare genetic disorder that affects the mitochondria, leading to various symptoms and complications. While there are no specific treatments available for MC4DN13, some medications have been used off-label or in combination with dietary supplements to manage its symptoms.

• Dietary Supplements: Dietary supplements such as CoQ10 and B vitamins may be recommended to support mitochondrial function [1][2].
• Bezafibrate: Bezafibrate, a fibrate drug, has been shown to increase mitochondrial biogenesis and may be considered for treatment in some cases [3].
• Valproate: Valproate, an anticonvulsant medication, has been used off-label to treat myoclonic epilepsy associated with MC4DN13 [6].

It's essential to note that these treatments are not specific to MC4DN13 and may be used in combination with other medications or dietary supplements. The effectiveness of these treatments can vary depending on the individual case.

References:

[1] S Avula (2014) - CoQ10 and a B vitamin are the most commonly used medications in a starting “mitochondrial treatment cocktail.” [Context 1]

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

[3] RJ Tinker (2021) - Bezafibrate is a fibrate drug that increases mitochondrial biogenesis. [Context 5]

[6] MIM number, Gene/Locus, Gene/Locus MIM number. 1q42.2 · Mitochondrial complex IV deficiency, nuclear type 13 ... treatment with valproate for myoclonic epilepsy, ... [Context 6]

Differential Diagnosis of Mitochondrial Complex IV Deficiency, Nuclear Type

Mitochondrial complex IV deficiency, nuclear type, is a rare genetic disorder that affects the functioning of mitochondria in cells. The differential diagnosis for this condition involves ruling out other possible causes of similar symptoms.

• Leigh disease: This is a heterogeneous group of conditions caused by autosomal recessively-inherited mutations in nuclear genes. It can present with similar symptoms to mitochondrial complex IV deficiency, including progressive neurodegeneration and muscle weakness [6].
• Complex II deficiency: Mutations in the SDHA gene can cause Leigh syndrome, which shares some clinical features with mitochondrial complex IV deficiency, such as epilepsy, optic atrophy, and cardiomyopathy [7].
• Mitochondrial DNA depletion syndromes: These are caused by defects in mtDNA maintenance due to pathogenic variants in nuclear genes. They can present with similar symptoms to mitochondrial complex IV deficiency, including hepatomegaly and hypertrophic cardiomyopathy [2].
• Other mitochondrial diseases: There are over 350 known genes that can cause mitochondrial disease, leading to a wide range of clinical presentations. A thorough diagnostic workup is necessary to rule out other possible causes of mitochondrial dysfunction [4].

Key Diagnostic Features

To diagnose mitochondrial complex IV deficiency, nuclear type, the following key features should be considered:

• Mitochondrial complex IV enzyme activity: This can be measured in muscle or liver tissue to confirm the diagnosis.
• Genetic testing: Sequencing of the COX4I2 gene and other genes involved in mitochondrial complex IV function can help identify pathogenic variants.
• Clinical presentation: A thorough medical history and physical examination are essential to rule out other possible causes of similar symptoms.

References

[1] Abnormal cellular phenotype. Decreased activity of mitochondrial complex I [2] by M Almannai · 2017 · Cited by 17 — Differential Diagnosis​​ Mitochondrial DNA depletion syndromes occur as a result of defects in mtDNA maintenance caused by pathogenic variants in ... [4] 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 ... [6] by JD Weisfeld-Adams · 2015 · Cited by 54 — Leigh disease encompasses a heterogeneous group of conditions, some of which are caused by autosomal recessively-inherited mutations in nuclear ... [7] by AC Goldstein · 2013 · Cited by 50 — Complex II deficiency due to SDHA mutations can cause Leigh syndrome, epilepsy, optic atrophy, ataxia, myopathy with exercise intolerance, cardiomyopathy, and ...