mitochondrial complex IV deficiency nuclear type 15

Mitochondrial complex IV deficiency, nuclear type 15 (MC4DN15) is an autosomal recessive multisystem disorder [1]. It affects various parts of the body, including the metabolism, cardiovascular system, and digestive system [2].

The clinical features of MC4DN15 include global developmental delay, poor feeding, short stature with microcephaly, proximal muscle weakness, and distal spasticity [3]. Other affected individuals may experience abnormality of metabolism/homeostasis, hyper-beta-alaninemia, and abnormalities in the respiratory system, head or neck, and eyes [4][5].

MC4DN15 is caused by a homozygous mutation in an unknown gene, leading to defective oxidative phosphorylation in mitochondria. It is inherited in an autosomal recessive manner, meaning that both parents must be carriers of the mutated gene for their offspring to develop the condition [6][7].

In one reported case, a patient with MC4DN15 was described as having mitochondrial complex IV deficiency nuclear type 15 [8]. Another study defined MC4DN15 as a COX deficiency, benign infantile mitochondrial myopathy caused by a homozygous mutation in the COX8A gene on chromosome 11q13.1 [9].

References: [1] - Context result 4 [2] - Context result 2 [3] - Context result 3 [4] - Context result 10 [5] - Context result 10 [6] - Context result 8 [7] - Context result 8 [8] - Context result 4 [9] - Context result 9

Clinical Features and Signs

Mitochondrial complex IV deficiency, nuclear type 15 (also known as COX8A-related mitochondrial myopathy) is a rare genetic disorder that affects the mitochondria's ability to produce energy for the body. The clinical features and signs of this condition can vary in severity and presentation.

• Global Developmental Delay: Affected individuals may experience significant delays in reaching developmental milestones, such as sitting, crawling, or walking [1].
• Poor Feeding: Some individuals with mitochondrial complex IV deficiency may have difficulty feeding due to poor appetite or swallowing problems [2].
• Short Stature and Microcephaly: People with this condition often have short stature and small head size (microcephaly) [3].
• Proximal Muscle Weakness: Affected individuals may experience weakness in the muscles of the upper arms, thighs, and other proximal muscle groups [4].
• Distal Spasticity: Some individuals may develop spasticity or stiffness in their hands and feet [5].

Other Possible Symptoms

In addition to these primary symptoms, some people with mitochondrial complex IV deficiency may experience:

• Low Muscle Tone (Hypotonia): Affected individuals may have low muscle tone, which can lead to poor posture or difficulty maintaining balance [6].
• Muscle Pain (Myalgia) and Fatigue: Some individuals may experience muscle pain or extreme fatigue after physical activity [7].
• Developmental Regression: In some cases, affected individuals may experience episodic developmental regression, where they temporarily lose previously acquired skills [8].

Important Note

It's essential to consult a medical professional for an accurate diagnosis and treatment plan. These symptoms can be indicative of various conditions, and only a qualified healthcare provider can determine the specific cause.

References:

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

Diagnostic Tests for Mitochondrial Complex IV Deficiency Nuclear Type 15

Mitochondrial complex IV deficiency nuclear type 15 (MC4DN15) is a rare genetic disorder that affects the mitochondria, the energy-producing structures within cells. Diagnosing this condition requires a combination of clinical evaluation, laboratory tests, and genetic analysis.

Laboratory Findings

• Elevated lactate levels in serum and cerebrospinal fluid [3]
• Reduced levels and activity of mitochondrial respiratory complex IV [3]

Genetic Testing

• Deletion/duplication analysis of the nuclear-encoded genes associated with mitochondrial dysfunction [2]
• Sequence analysis of the genes encoding mitochondrial proteins [2]

Clinical Tests

• Molecular Genetics Tests, including deletion/duplication analysis and sequence analysis [4]

These diagnostic tests can help confirm a diagnosis of MC4DN15 and provide valuable information for genetic counseling and family planning.

References:

[1] The Invitae Nuclear Mitochondrial Disorders Panel analyzes nuclear-encoded genes associated with mitochondrial dysfunction. [2] 4 tests are in the database for this condition, including deletion/duplication analysis and sequence analysis of the genes encoding mitochondrial proteins. [3] Laboratory findings show elevated lactate levels in serum and cerebrospinal fluid, along with reduced levels and activity of mitochondrial respiratory complex IV. [4] Clinical tests include molecular genetics tests, such as deletion/duplication analysis and sequence analysis.

Current Treatment Options for Mitochondrial Complex IV Deficiency, Nuclear Type 15

Mitochondrial complex IV deficiency, nuclear type 15 is a rare genetic disorder that affects the mitochondria's ability to produce energy in cells. While there are no specific treatments approved for this condition, researchers have explored various therapeutic approaches.

• Off-label use of medications: According to search results [6], all treatment of mitochondrial disorders, including complex IV deficiency, is currently performed with dietary supplements or off-label use of drugs approved for other indications.
• Dietary supplements: Some studies suggest that certain dietary supplements may help alleviate symptoms. However, more research is needed to confirm their effectiveness.
• Bezafibrate: A study published in [5] found that bezafibrate, a fibrate drug, increases mitochondrial biogenesis and may be beneficial for treating complex IV deficiency.

Important Note

It's essential to consult with a healthcare professional or a specialist in mitochondrial disorders for personalized advice on managing this condition. They can help determine the best course of treatment based on individual circumstances.

References:

[5] RJ Tinker (2021) Bezafibrate: A Review of its Pharmacology and Therapeutic Potential [Cited by 65]

[6] O Hurko (2013) Treatment of Mitochondrial Disorders [Cited by 14]

Mitochondrial Complex IV Deficiency Nuclear Type 15 (MC4DN15)

Mitochondrial Complex IV Deficiency, Nuclear Type 15 (MC4DN15) is a rare genetic disorder caused by mutations in the COX5A gene. This condition affects the mitochondria's ability to produce energy for the body.

Differential Diagnosis

The differential diagnosis of MC4DN15 includes other mitochondrial diseases that affect Complex IV activity. Some of these conditions include:

• Mitochondrial DNA-associated Leigh syndrome: A rare genetic disorder caused by mutations in the mitochondrial DNA, leading to impaired Complex IV activity.
• Complex multisystem disease: A condition characterized by widespread tissue damage and dysfunction, which may be secondary to carnitine deficiency in Primary Mitochondrial Diseases (PMD).
• Leigh syndrome: A severe neurodegenerative disorder caused by mutations in various genes, including SDHA, which can lead to Complex II deficiency.

Key Features

The key features of MC4DN15 include:

• Mitochondrial dysfunction: Impaired energy production due to COX5A gene mutations.
• Complex IV deficiency: Reduced activity of the mitochondrial enzyme cytochrome c oxidase (COX).
• Recessive inheritance pattern: The condition 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.

Biomarkers

Some biomarkers associated with MC4DN15 include:

• FGF21 and GDF15: Elevated levels of these proteins in the blood may indicate mitochondrial dysfunction.
• Blood tests: Abnormalities in blood tests, such as decreased carnitine levels, may suggest a diagnosis of MC4DN15.

References

1. [8] Mitochondrial Complex IV Deficiency, Nuclear Type 20 (MC4DN20) (Complex IV)
2. [9] by S Rahman · 2020 · Cited by 150 — ... differential diagnosis of complex multisystem disease; may be secondary carnitine deficiency in PMD.
3. [10] 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 ...