nuclear type mitochondrial complex I deficiency 8

Mitochondrial Complex I Deficiency, Nuclear Type 8: An Overview

Mitochondrial complex I deficiency, nuclear type 8 (MC1DN8) is a form of mitochondrial disorder characterized by defective oxidative phosphorylation. This condition affects the functioning of mitochondria, which are the energy-producing structures within cells.

Causes and Genetics

The MC1DN8 is caused by homozygous or compound heterozygous mutation in the NDUFS3 gene on chromosome 11p11 [2][5]. The NDUFS3 gene plays a crucial role in encoding a subunit of complex I, which is essential for mitochondrial function.

Clinical Features

The clinical features of MC1DN8 can vary widely among affected individuals. However, it often presents with progressive neurodegenerative disorders, particularly in organs and tissues that rely heavily on oxidative phosphorylation [11]. This can lead to a range of symptoms, including muscle weakness, seizures, and developmental delays.

Diagnosis and Management

A diagnosis of MC1DN8 is typically made through genetic testing, which involves analyzing the NDUFS3 gene for mutations. Clinical genetic specialists may also recommend specific tests to help reach a diagnosis [10]. While there is no cure for MC1DN8, management strategies focus on addressing the underlying mitochondrial dysfunction and alleviating symptoms.

Prevalence and Impact

Mitochondrial complex I deficiency, including nuclear type 8, is one of the most common biochemical signatures of mitochondrial disorders. It affects approximately 1 in 5-10 individuals with mitochondrial diseases [4][8]. The impact of MC1DN8 on affected individuals and their families can be significant, highlighting the need for early diagnosis and management.

References

[1] Mitochondrial complex I deficiency is a shortage (deficiency) of a protein complex called complex I or a loss of its function. Complex I is found in cell structures called mitochondria, which convert the energy from food into a form that cells can use. [2] A number sign (#) is used with this entry because of evidence that mitochondrial complex I deficiency nuclear type 8 (MC1DN8) is caused by homozygous or compound heterozygous mutation in the NDUFS3 gene (603846) on chromosome 11p11. [4] Mitochondrial complex I deficiency, nuclear type 8 is a form of mitochondrial disorder characterized by defective oxidative phosphorylation. It affects 1 in 5-... [10] To find out if someone has a diagnosis of Mitochondrial Complex I, Deficiency, Nuclear Type, it is important to have a consultation and evaluation with a clinical genetic specialist. [11] Defects of complex I, the largest enzyme complex in the RC, are among the most common causes of mitochondrial diseases. Often presenting at birth or in early childhood, complex I deficiency usually causes progressive neuro-degenerative disorders...

Signs and Symptoms of Nuclear Type Mitochondrial Complex I Deficiency

Nuclear type mitochondrial complex I deficiency can manifest in various ways, depending on the severity and location of the affected cells. Some common signs and symptoms include:

• Decreased activity of mitochondrial complex I: This is a hallmark feature of nuclear type mitochondrial complex I deficiency.
• Hyper-beta-alaninemia: Elevated levels of beta-alanine in the blood can be indicative of this condition.
• Increased circulating lactate concentration: High levels of lactic acid in the bloodstream are often associated with mitochondrial complex I deficiency.
• Gastroesophageal reflux: Some individuals may experience symptoms of gastroesophageal reflux, such as heartburn and regurgitation.

These signs and symptoms can vary in severity and may be accompanied by other clinical features, depending on the specific genetic mutation involved. It's essential to consult with a clinical genetic specialist for an accurate diagnosis and evaluation.

References:

• [4] - Decreased activity of mitochondrial complex I
• [6] - Hyper-beta-alaninemia
• [7] - Increased circulating lactate concentration
• [8] - Gastroesophageal reflux

Diagnostic Tests for Nuclear Type Mitochondrial Complex I Deficiency

Nuclear type mitochondrial complex I deficiency can be diagnosed through various genetic tests that analyze the NDUFS4 gene, which is responsible for encoding a subunit of the mitochondrial complex I. Here are some diagnostic tests that may be used to diagnose this condition:

• Sequence analysis of the entire coding region: This test involves analyzing the entire coding region of the NDUFS4 gene to identify any mutations or variations that may be causing the deficiency. [12]
• Bi-directional Sanger Sequence Analysis: This is a type of sequence analysis that involves sequencing both strands of DNA to ensure accurate results. It can be used to diagnose nuclear type mitochondrial complex I deficiency by identifying mutations in the NDUFS4 gene. [12]

It's worth noting that the diagnosis of nuclear type mitochondrial complex I deficiency often requires a combination of clinical evaluation, family history, and genetic testing. A consultation with a clinical genetic specialist is recommended to determine the best course of action for diagnosis and treatment.

References:

[8] Guidelines for the analysis of mtDNA and nuclear-encoded genes in patients with suspected mitochondrial disorders. [Mavraki E, 2023]

[12] Clinical Molecular Genetics test for Mitochondrial complex I deficiency, nuclear type 1. Translational Metabolic Laboratory.

Treatment Options for Nuclear Type Mitochondrial Complex I Deficiency

According to various sources, there are several treatment options available for nuclear type mitochondrial complex I deficiency.

• CoQ10: Patients with primary mitochondrial disorders should be offered CoQ10 in its reduced form (ubiquinol), as per recommendations [6].
• Dietary Supplements: Treatment of mitochondrial disorders is often performed with dietary supplements or off-label use of drugs approved for other indications [7].
• Riboflavin, Thiamine, Biotin, and Carnitine: A variety of treatments, which may or may not be effective, include riboflavin, thiamine, biotin, CoQ10, and carnitine [11].

It's essential to note that these treatment options are not a cure for complex I deficiency but rather an attempt to manage the symptoms. The effectiveness of these treatments can vary depending on individual cases.

References: [6] - According to these recommendations, patients with primary mitochondrial disorders should be offered CoQ10 in its reduced form (ubiquinol), and plasma or ... [7] - by O Hurko · 2013 · Cited by 14 — Currently, all treatment of mitochondrial disorders is performed with dietary supplements or by off-label use of drugs approved for other indications. [11] - A variety of treatments, which may or may not be effective, include: riboflavin, thiamine, biotin, CoQ10, and carnitine.