nuclear type mitochondrial complex I deficiency 7

Mitochondrial Complex I Deficiency, Nuclear Type 7 (MC1DN7)

Mitochondrial complex I deficiency, nuclear type 7 is a rare genetic disorder caused by mutations in the NDUFV2 gene on chromosome 18p11. This condition affects the mitochondria's ability to produce energy for the cell, leading to various clinical features.

Clinical Features:

• Decreased activity of mitochondrial complex I
• Lactic acidosis (elevated levels of lactic acid in the blood)
• Hypertrophic cardiomyopathy (enlarged heart)
• Feeding difficulties
• Nystagmus (involuntary eye movements)
• Optic atrophy (damage to the optic nerve)

Causes:

The condition is caused by homozygous or compound heterozygous mutations in the NDUFV2 gene, which codes for a subunit of mitochondrial complex I. This mutation affects the mitochondria's ability to produce energy, leading to the various clinical features associated with this disorder.

Prevalence: Unfortunately, there is limited information available on the prevalence of MC1DN7. However, it is considered a rare condition.

References:

• [1] Mitochondrial complex I deficiency, nuclear type 7 is caused by mutations in the NDUFV2 gene (600532) on chromosome 18p11.
• [3] Clinical features include decreased activity of mitochondrial complex I, lactic acidosis, hypertrophic cardiomyopathy, feeding difficulties, nystagmus, and optic atrophy.
• [14] Complex I deficiency is the most frequently encountered single mitochondrial enzyme deficiency in patients with a mitochondrial disorder.

Clinical Features of Mitochondrial Complex I Deficiency Nuclear Type 7

Mitochondrial complex I deficiency, nuclear type 7 (MC1DN7), is a genetic disorder characterized by a shortage or loss of function of the protein complex called complex I in the mitochondria. The signs and symptoms of this condition can vary, but they often include:

• Decreased activity of mitochondrial complex I: This is the underlying cause of the disorder, leading to impaired energy production in cells.
• Lactic acidosis: A buildup of lactic acid in the blood, which can lead to various complications.
• Hypertrophic cardiomyopathy: An enlarged heart muscle that can lead to heart failure.
• Feeding difficulties: Problems with feeding and eating due to muscle weakness or other symptoms.
• Nystagmus: Involuntary eye movements.
• Optic atrophy: Damage to the optic nerve, leading to vision problems.

These symptoms can be present from birth or may develop later in life. The severity of the condition can vary greatly among affected individuals.

References:

• [2] Clinical features · Decreased activity of mitochondrial complex I · Lactic acidosis · Hypertrophic cardiomyopathy · Feeding difficulties · Nystagmus · Optic atrophy.
• [6] A number sign (#) is used with this entry because of evidence that mitochondrial complex I deficiency nuclear type 7 (MC1DN7) is caused by homozygous or compound heterozygous mutation in the gene responsible for the structural subunit of mitochondrial oxidative phosphorylation system I.

Diagnostic Tests for Mitochondrial Complex I Deficiency, Nuclear Type 7

Mitochondrial complex I deficiency, nuclear type 7 (MC1DN7) is a genetic disorder that affects the functioning of the mitochondria in cells. The diagnosis of this condition typically involves a combination of clinical evaluation and molecular testing.

• Genetic Testing: Genetic testing can confirm the presence of mutations in the NDUFS4 gene, which is associated with MC1DN7. This test can be performed using various methods, including deletion/duplication analysis (10) [2].
• Exome Sequencing: Exome sequencing is a comprehensive genetic test that analyzes all the protein-coding regions of the genome. It can identify mutations in the NDUFS4 gene and other genes associated with mitochondrial complex I deficiency [8].
• Sequence Analysis: Sequence analysis of the entire coding region of the NDUFS4 gene can also be performed to confirm the presence of mutations [15].

Clinical Evaluation

A clinical genetic specialist may perform a consultation and evaluation to assess symptoms and medical history. They may also suggest specific genetic testing or other types of tests to help reach a diagnosis.

• Muscle Tone and Fatigue: Affected individuals may have low muscle tone (hypotonia), muscle pain (myalgia), and extreme fatigue in response to physical activity (exercise intolerance) [6].
• Clinical Features: The clinical features of MC1DN7 can be found on various online resources, including GeneReviews, PubMed, MedlinePlus, and clinicaltrials.gov [11][13].

Important Considerations

It is essential to consult with a clinical genetic specialist for an accurate diagnosis. They may recommend specific genetic testing or other types of tests to help reach a diagnosis.

• Genetic Testing: Genetic testing should be performed by a qualified laboratory to ensure accuracy and reliability.
• Clinical Evaluation: A thorough clinical evaluation by a clinical genetic specialist is crucial for an accurate diagnosis.

References:

[2] - Deletion/duplication analysis (10) [6] - Affected individuals may have low muscle tone (hypotonia), muscle pain (myalgia), and extreme fatigue in response to physical activity (exercise intolerance). [8] - Mitochondrial complex I deficiency shows extreme genetic heterogeneity and can be caused by mutation in nuclear-encoded genes or in mitochondrial-encoded genes. [11] - Clinical resource with information about Mitochondrial complex I deficiency nuclear type 1 and its clinical features, NDUFS4, available genetic tests from US and labs around the world and links to practice guidelines and authoritative resources like GeneReviews, PubMed, MedlinePlus, clinicaltrials.gov, PharmGKB [13] - Clinical resource with information about Mitochondrial complex I deficiency nuclear type and its clinical features, available genetic tests from US and labs around the world and links to practice guidelines and authoritative resources like GeneReviews, PubMed, MedlinePlus, clinicaltrials.gov, PharmGKB [15] - Clinical Molecular Genetics test for Mitochondrial complex I deficiency, nuclear type 1 and using Sequence analysis of the entire coding region, Bi-directional Sanger Sequence Analysis offered by Translational Metabolic Laboratory.

Treatment Options for Nuclear Type Mitochondrial Complex I Deficiency

According to available information, there are currently limited treatment options for nuclear type mitochondrial complex I deficiency. However, some dietary supplements and off-label use of drugs have been explored as potential treatments.

• Dietary Supplements: Certain metabolic therapies such as riboflavin, thiamine, biotin, co-enzyme Q10 (CoQ10), carnitine, and others may be considered as part of a treatment plan. However, their effectiveness can vary greatly from person to person.
• Off-label Use of Drugs: Some medications approved for other indications have been used off-label to treat mitochondrial disorders. This approach requires careful consideration and monitoring due to potential side effects.

It's essential to note that these treatments may not be effective for everyone and should be discussed with a healthcare professional before initiation.

Differential Diagnosis of Mitochondrial Complex I Deficiency Nuclear Type 7

Mitochondrial complex I deficiency nuclear type 7 (MC1DN7) is a rare genetic disorder caused by mutations in the nuclear-encoded genes responsible for the assembly and function of mitochondrial complex I. The differential diagnosis of MC1DN7 involves distinguishing it from other mitochondrial disorders, as well as conditions that may present with similar clinical features.

Similar Mitochondrial Disorders:

• Mitochondrial Complex I Deficiency: This is a more common form of mitochondrial complex I deficiency caused by mutations in the mitochondrial DNA. It presents with similar clinical features to MC1DN7, including encephalopathy, cardiomyopathy, and myopathy.
• Leigh Syndrome: A severe neurodegenerative disorder caused by mutations in either nuclear or mitochondrial genes encoding for components of the mitochondrial respiratory chain. Clinical manifestations include subacute necrotizing encephalopathy, cardiomyopathy, and liver disease.

Other Conditions:

• Mitochondrial Myopathies: A group of disorders characterized by muscle weakness and wasting due to impaired mitochondrial function.
• Neurodegenerative Disorders: Such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, which may present with similar clinical features to MC1DN7.

Key Diagnostic Features:

• Genetic Testing: Molecular genetic testing is essential for diagnosing MC1DN7. This involves sequencing the nuclear-encoded genes responsible for complex I assembly and function.
• Biochemical Markers: Elevated levels of lactate, pyruvate, and other metabolites in the blood or cerebrospinal fluid may indicate mitochondrial dysfunction.
• Imaging Studies: MRI and CT scans can reveal abnormalities in brain structure and function.

References:

[1] A deficiency of the mitochondrial respiratory chain enzyme complex I (NADH:ubiquinone oxidoreductase) is the most frequently encountered single enzyme deficiency causing mitochondrial disorders [1]. [3] Here, we present a comprehensive overview of clinical, biochemical and cell physiological information of 15 children with isolated, nuclear-encoded complex I deficiency, which was generated in a joint effort of clinical and fundamental research. [7] A number sign (#) is used with this entry because of evidence that mitochondrial complex I deficiency nuclear type 7 (MC1DN7) is caused by homozygous or compound heterozygous mutations in the NDUFB11 gene [7]. [8] Isolated complex I deficiency is the most frequently observed mitochondrial respiratory chain disorder, and is associated with a wide range of clinical manifestations [8].