nuclear type mitochondrial complex I deficiency 26

Mitochondrial Complex I Deficiency Nuclear Type 26

Mitochondrial complex I deficiency nuclear type 26 (MC1DN26) is a rare genetic disorder that affects the mitochondria, the energy-producing structures within cells. This condition is characterized by a shortage or deficiency of a protein complex called complex I, which is essential for the proper functioning of the mitochondria.

Clinical Features

The clinical features of MC1DN26 can vary widely among affected individuals, but may include:

• Poor muscle tone: Weakness and floppiness in muscles
• Developmental delay: Slowed or delayed development, including speech and language skills
• Heart disease: Abnormalities in the heart's structure and function
• Lactic acidosis: Elevated levels of lactic acid in the blood
• Respiratory failure: Difficulty breathing and respiratory distress

Causes and Genetics

MC1DN26 is caused by a mutation in one of the nuclear genes that codes for a structural subunit of mitochondrial complex I. This mutation leads to a deficiency or dysfunction of the complex, resulting in impaired energy production within cells.

The condition is inherited in an autosomal recessive pattern, meaning that both parents must be carriers of the mutated gene for their child to inherit the condition.

Diagnosis and Treatment

A diagnosis of MC1DN26 can be made through genetic testing, which involves analyzing DNA samples from affected individuals. There is currently no cure for this condition, but treatment may involve managing symptoms and supporting the individual with the condition.

• Genetic testing: Analysis of DNA samples to confirm the presence of the mutated gene
• Symptom management: Treatment of specific symptoms, such as heart disease or respiratory failure
• Supportive care: Provision of supportive care, including physical therapy and speech therapy

References

• [1] (no direct reference available)
• [14] Mitochondrial complex I deficiency is a genetic disorder caused by a mutation in both nuclear and mitochondrial genes coding for structural subunits of mitochondrial oxidative phosphorylation system I (OXPHOS complex) and associated factors involved in the assembly and function of the complex, leading to a wide array of clinical manifestation including Leigh syndrome, MELAS (mitochondrial encephalomyelitis, lactic acidosis, and stroke-like episodes), and other conditions.
• [15] Mitochondrial complex I deficiency nuclear type 39 (MC1DN39) is an autosomal recessive nuclear disorder of mitochondrial respiratory chain complex I characterized by intrauterine growth retardation and anemia and postpartum hypertrophic cardiomyopathy, lactic acidosis, encephalopathy, and a severe complex I defect with a fatal outcome.

Based on the provided context, here are the signs and symptoms of nuclear type mitochondrial complex I deficiency:

• Acute metabolic acidosis: This is a condition characterized by an excessive accumulation of acidic substances in the body (1).
• Hypertrophic cardiomyopathy: This refers to a thickening of the heart muscle that can lead to problems with the heart's ability to pump blood effectively (3).
• Muscle weakness: Muscle weakness, particularly in the muscles used for movement and other bodily functions, is a common symptom of mitochondrial complex I deficiency (4, 5).
• Hyper-beta-alaninemia: This is an elevated level of beta-alanine in the blood, which can be indicative of mitochondrial dysfunction (4, 6).
• Increased circulating lactate concentration: Elevated levels of lactic acid in the blood are a hallmark of mitochondrial complex I deficiency (4, 6).
• Gastroesophageal reflux: This is a condition characterized by stomach acid flowing back up into the esophagus, which can cause discomfort and other symptoms (4).

It's worth noting that these symptoms can vary greatly from person to person and may not be present in all individuals with nuclear type mitochondrial complex I deficiency.

Based on the provided context, here are some diagnostic tests for nuclear type mitochondrial complex I deficiency:

• Sequence analysis of the entire coding region: This test is offered by Translational Metabolic Laboratory and involves bi-directional Sanger Sequence Analysis (context #12).
• Genetic testing: Clinical genetic specialists may suggest specific genetic testing to help reach a diagnosis (context #10).
• Muscle biopsy: Spectrophotometric measurements of the enzyme in a muscle biopsy can be used to establish complex I deficiency in patients (context #7).

It's also worth noting that the Invitae Nuclear Mitochondrial Disorders Panel analyzes nuclear-encoded genes associated with mitochondrial dysfunction, which may include testing for nuclear type mitochondrial complex I deficiency (context #5).

Additionally, clinical resources such as GeneReviews, PubMed, MedlinePlus, and PharmGKB provide information on diagnostic tests and guidelines for mitochondrial complex I deficiency (contexts #2 and #12).

Please note that these tests should only be performed under the guidance of a qualified healthcare professional.

Based on the provided context, here are some potential drug treatments for nuclear type mitochondrial complex I deficiency:

• Riboflavin: According to search result [11], riboflavin is one of the treatments that may or may not be effective for complex I deficiency.
• Thiamine: Thiamine is another treatment mentioned in search result [11] as a potential option for treating complex I deficiency.
• Biotin: Biotin is also listed in search result [11] as a possible treatment for complex I deficiency, although its effectiveness may vary.
• CoQ10: Coenzyme Q10 (CoQ10) is mentioned in search result [8] as a potential therapeutic option for mitochondrial respiratory chain dysfunction, which may be relevant to complex I deficiency.
• Carnitine: Carnitine is also listed in search result [11] as a possible treatment for complex I deficiency.

It's essential to note that these treatments may not be effective for everyone and should be discussed with a healthcare professional before initiation. Additionally, recent developments mentioned in search result [13] have shown promising new therapeutic strategies in vitro and have entered clinical trials, which may offer more targeted and effective treatments in the future.

References: [8], [11], [13]

Differential Diagnosis of Nuclear Type Mitochondrial Complex I Deficiency

Mitochondrial complex I deficiency, particularly the nuclear type, is a rare genetic disorder that affects the energy-producing structures within cells. When considering the differential diagnosis for this condition, several factors and symptoms come into play.

• Progressive Multisystem Disorder: Mitochondrial dysfunction should be considered in the differential diagnosis of any progressive multisystem disorder [1].
• Cardiomyopathy: The nuclear mutations can cause hypertrophic cardiomyopathy, which is a thickening of the heart muscle that can lead to heart failure [5].
• Lactic Acidosis: A deficiency of complex I can cause lactic acidosis, which is an accumulation of lactic acid in the blood and tissues [9].
• Neurological Diseases: Complex I deficiency can also cause neurologic diseases such as Leigh syndrome, a rare genetic disorder that affects the nervous system [9].

Key Considerations

When differentiating between various conditions, it's essential to consider the following:

• Genetic Mutations: The presence of specific genetic mutations in the NDUFAF5 gene can indicate mitochondrial complex-I deficiency, nuclear type 16 [8].
• Clinical Characteristics: A thorough understanding of clinical and investigational characteristics is crucial for accurate diagnosis [6].

References

[1] PF Chinnery. Mitochondrial dysfunction should be considered in the differential diagnosis of any progressive multisystem disorder.

[5] AC Goldstein. The nuclear mutations can cause hypertrophic cardiomyopathy, hypotonia, lactic acidosis, 3-methylglutaconic acid in urine, hyperammonemia, and epilepsy.

[6] JD Weisfeld-Adams. Here we review single gene disorders that have the potential to mimic multiple sclerosis, provide an overview of clinical and investigational characteristics.

[8] Sep 18, 2023. Mitochondrial complex-I deficiency, nuclear type 16, is a rare form of complex-I deficiency, caused by biallelic pathogenic variants in NDUFAF5.

[9] M Naber. A deficiency of complex I can cause a wide range of diseases, such as cardiomyopathy, neurologic diseases (e.g. Leigh syndrome) and myopathy, accompanied by lactic acidosis.