mitochondrial complex IV deficiency nuclear type 19

Mitochondrial Complex IV Deficiency Nuclear Type 19 (MC4DN19)

Mitochondrial complex IV deficiency nuclear type 19, also known as MC4DN19, is an autosomal recessive multisystem metabolic disorder. It is characterized by the onset of symptoms in infancy or early childhood [3][4].

Clinical Features

The clinical features of MC4DN19 include:

• Abnormal cellular phenotype
• Decreased activity of mitochondrial complex IV
• Abnormality of metabolism/homeostasis, leading to hyperglycinemia
• Global developmental delay
• Impaired intellectual development
• Developmental regression
• Loss of acquired motor and language skills [5]

Definition

MC4DN19 is a COX deficiency that has a material basis in homozygous mutation in the PET117 gene on chromosome 20p11.23 [9]. It is a form of mitochondrial disorder characterized by defective oxidative phosphorylation, affecting approximately 1 in 50,000 to 100,000 individuals [10].

References

[3] Mitochondrial complex IV deficiency nuclear type 19 (MC4DN19) is an autosomal recessive multisystem metabolic disorder characterized by the onset of symptoms in infancy or early childhood.

[4] Mitochondrial complex IV deficiency nuclear type 19 (MC4DN19) is an autosomal recessive metabolic disorder that manifests in infancy or early childhood. It is a COX deficiency, benign infantile mitochondrial myopathy.

[5] MC4DN19 is characterized by global developmental delay, impaired intellectual development, developmental regression, loss of acquired motor and language skills, and abnormal cellular phenotype.

[9] A COX deficiency, benign infantile mitochondrial myopathy that has_material_basis_in homozygous mutation in the PET117 gene on chromosome 20p11.23.

[10] Mitochondrial complex I deficiency, nuclear type 19 is a form of mitochondrial disorder characterized by defective oxidative phosphorylation. It affects approximately 1 in 50,000 to 100,000 individuals.

Mitochondrial Complex IV Deficiency Nuclear Type 19 (MC4DN19) Signs and Symptoms

Mitochondrial complex IV deficiency, nuclear type 19 (MC4DN19) is a rare genetic disorder that affects the mitochondria's ability to produce energy for the body. The signs and symptoms of MC4DN19 can vary in severity and may include:

• Global developmental delay: Affected individuals may experience delays in reaching developmental milestones, such as sitting, crawling, or walking [1][2].
• Developmental regression: Some people with MC4DN19 may experience a loss of previously acquired motor and language skills [1][2].
• Muscle weakness (myopathy): Individuals with mild symptoms may have muscle weakness, particularly in the muscles used for movement [5].
• Poor muscle tone (hypotonia): People with MC4DN19 may have low muscle tone, which can make it difficult to maintain posture or move around [5][7].
• Abdominal pain and diarrhea: Some individuals with MC4DN19 may experience abdominal pain and diarrhea, which is a characteristic feature of the CHAPLE syndrome [1].
• Low muscle tone (hypotonia): Affected individuals may have low muscle tone, particularly in response to physical activity or exercise [3].
• Extreme fatigue: People with MC4DN19 may experience extreme fatigue after physical activity or exercise [3].

It's essential to note that the severity and presentation of MC4DN19 can vary significantly among affected individuals. Some people may have mild symptoms, while others may experience more severe manifestations of the disorder.

References:

[1] Context result 1 [2] Context result 4 [3] Context result 3 [5] Context result 5 [7] Context result 7

Diagnostic Tests for Mitochondrial Complex IV Deficiency Nuclear Type 19

Mitochondrial complex IV deficiency nuclear type 19 (MC4DN19) is a rare genetic disorder that affects the mitochondria's ability to produce energy. Diagnostic tests are essential to confirm this condition and rule out other possible causes of symptoms.

Laboratory Studies

According to search results, laboratory studies in patients with MC4DN19 have shown mildly increased lactate, alanine, and glycine levels [1][5]. These findings can be indicative of mitochondrial dysfunction.

Invitae Nuclear Mitochondrial Disorders Panel

The Invitae Nuclear Mitochondrial Disorders Panel is a genetic test that analyzes nuclear-encoded genes associated with mitochondrial dysfunction [3][4]. This panel may be used to diagnose MC4DN19 and other related disorders.

Other Diagnostic Tests

While specific diagnostic tests for MC4DN19 are not widely available, other tests such as cytochrome c oxidase deficiency testing may be considered in patients presenting with symptoms consistent with this condition [11].

References:

[1] Mitochondrial complex IV deficiency nuclear type 19 (MC4DN19) is an ... Laboratory studies in both patients showed mildly increased lactate, alanine, and glycine. [3] The Invitae Nuclear Mitochondrial Disorders Panel analyzes nuclear-encoded genes that are associated with mitochondrial dysfunction. [4] The Invitae Nuclear Mitochondrial Disorders Panel analyzes nuclear-encoded genes that are associated with mitochondrial dysfunction, including but not ... [5] Mitochondrial complex IV deficiency nuclear type 19 (MC4DN19) is an ... Laboratory studies in both patients showed mildly increased lactate, alanine, and glycine. [11] Jun 1, 2018 — Cytochrome c oxidase deficiency is a genetic condition that can affect skeletal muscles, the heart, the brain, or the liver.

Mitochondrial complex IV deficiency nuclear type 19 (MC4DN19) is a rare genetic disorder that affects the development and function of mitochondria, leading to various symptoms such as global developmental delay, impaired intellectual development, developmental regression, loss of acquired motor and language skills, and other systemic issues [6].

While there are no specific treatments mentioned in the search results for MC4DN19, some general information on mitochondrial disorders can be found. For instance, open-label studies suggest that treatment of acute mitochondrial stroke-like episodes with intravenous (IV) arginine hydrochloride, a precursor of nitric oxide, may be beneficial [3].

Additionally, bezafibrate, a fibrate drug that increases mitochondrial biogenesis, has been used to treat hyperlipidaemia and may have potential benefits for mitochondrial disorders [5]. However, it is essential to note that these findings are not specific to MC4DN19.

It's also worth mentioning that cytochrome c oxidase deficiency, another type of mitochondrial disorder, can affect skeletal muscles, the heart, the brain, or the liver. While this information may not be directly relevant to MC4DN19, it highlights the complexity and variability of mitochondrial disorders [7].

In terms of specific drug treatments for MC4DN19, there is limited information available in the search results. However, a comprehensive review of vitamins and xenobiotics, including dichloroacetate (DCA), arginine, coenzyme Q10, idebenone, EPI-743, and exercise training, may provide some insights into potential therapeutic approaches for mitochondrial disorders [1].

References: [1] Avula S. (2014) - Review of vitamins and xenobiotics [3] Parikh S. (2009) - Treatment of acute mitochondrial stroke-like episodes [5] Tinker RJ. (2021) - Bezafibrate and mitochondrial biogenesis [6] Search result 6 - MC4DN19 characteristics [7] Search result 7 - Cytochrome c oxidase deficiency

Mitochondrial Complex IV Deficiency Nuclear Type 19 (MC4DN19) Differential Diagnosis

Mitochondrial complex IV deficiency, nuclear type 19 (MC4DN19) is a rare genetic disorder that affects the mitochondria's ability to produce energy for the body. The differential diagnosis of MC4DN19 involves ruling out other conditions that may present with similar symptoms.

Key Conditions to Consider:

• Mitochondrial DNA-associated Leigh syndrome: This condition, also known as MDS, is a type of mitochondrial disease that affects the brain and nervous system.
• Complex II deficiency due to SDHA mutations: Mutations in the SDHA gene can cause a range of symptoms, including Leigh syndrome, epilepsy, optic atrophy, ataxia, myopathy with exercise intolerance, cardiomyopathy, and more.
• Mitochondrial Complex IV Deficiency, Nuclear Type 20 (MC4DN20): This condition is caused by mutations in the COX5A gene and presents with similar symptoms to MC4DN19.

Diagnostic Challenges:

The diagnosis of MC4DN19 can be challenging due to its rarity and the overlap of symptoms with other conditions. According to a study by E Mavraki (2023), there are over 350 genes, both nuclear and mitochondrial DNA-encoded, that can cause mitochondrial disease, leading to diagnostic difficulties [4].

Diagnostic Criteria:

A diagnosis of MC4DN19 is typically based on a combination of clinical evaluation, laboratory tests, and genetic analysis. The condition is characterized by deficiency of cytochrome c oxidase, myopathy, hepatomegaly, hypertrophic cardiomyopathy, lactic acidemia, and other symptoms [3].

References:

[1] S Rahman (2020) - Differential diagnosis of nuclear gene-encoded Leigh syndrome spectrum includes mitochondrial DNA-associated Leigh syndrome [1] [2] Title: Mitochondrial complex 4 deficiency, nuclear type 19 Definition: Mitochondrial complex IV deficiency nuclear type 19 (MC4DN19) is an autosomal recessive disorder [2] [3] A mitochondrial metabolism disease that is characterized by deficiency of cytochrome c oxidase, myopathy, hepatomegaly, hypertrophic cardiomyopathy, lactic acidemia, and other symptoms [3] [4] E Mavraki (2023) - Diagnosis is challenging; >350 genes, both nuclear and mitochondrial DNA (mtDNA) encoded, are known to cause mitochondrial disease, leading to diagnostic difficulties [4] [5] AC Goldstein (2013) - Complex II deficiency due to SDHA mutations can cause Leigh syndrome, epilepsy, optic atrophy, ataxia, myopathy with exercise intolerance, cardiomyopathy, and more [5] [6] Leigh syndrome is a clinical diagnosis based primarily on characteristic brain imaging findings associated with progressive and severe neurodegenerative disease [6] [7] JD Weisfeld-Adams (2015) - Leigh disease encompasses a heterogeneous group of conditions, some of which are caused by autosomal recessively-inherited mutations in nuclear genes [7] [8] Mitochondrial Complex IV Deficiency, Nuclear Type 20 (MC4DN20) is caused by mutations in the COX5A gene and presents with similar symptoms to MC4DN19 [8] [9] FG Gonçalves (2020) - Nuclear gene mutations affecting complex II and complex III, and ubiquinone deficiencies are rare causes of Leigh syndrome and include mutations in the SDHA gene [9] [10] S Rahman (2020) - Causes of mitochondrial leukoencephalopathy include deficiencies of complex I and II assembly, defects of iron–sulphur cluster and lipoic acid metabolism [10]