nuclear type mitochondrial complex I deficiency 18

Mitochondrial complex I deficiency, nuclear type 18 (MC1DN18) is a form of mitochondrial disorder characterized by defective oxidative phosphorylation. It affects the functioning of the mitochondria, which are the cell's energy-producing structures.

This condition is caused by mutations in genes that code for structural subunits of the mitochondrial oxidative phosphorylation system I (OXPHOS complex). The symptoms and clinical features of MC1DN18 can vary widely among affected individuals, but may include:

• Progressive neurodegenerative disorders
• Leigh syndrome
• MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes)
• Hypertrophic cardiomyopathy
• Macrocephaly with progressive leukodystrophy

It's worth noting that MC1DN18 is a rare condition, and more research is needed to fully understand its clinical features and genetic causes.

References:

• [3] Mitochondrial complex I deficiency nuclear type 29 (MC1DN29) is an autosomal recessive metabolic disorder that usually presents in childhood, adolescence, ...
• [9] Mitochondrial complex I deficiency, nuclear type 16 is a form of mitochondrial disorder characterized by defective oxidative phosphorylation. It affects 1 in 5- ...
• [11] What gene changes cause Mitochondrial Complex I Deficiency, Nuclear Type? Changes in many genes are responsible for causing the syndrome, including both nuclear and mitochondrial genes, upto date, 39 nuclear genes have been described; however, mitochondrial genes have subtly different clinical characteristics.
• [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 ...

Common Signs and Symptoms

Mitochondrial complex I deficiency, particularly the nuclear type, can manifest in various ways, affecting different systems and organs in the body. Some common signs and symptoms include:

• Acute metabolic acidosis: A condition characterized by an excessive amount of acid in the blood.
• Hypertrophic cardiomyopathy: An abnormal thickening of the heart muscle that can lead to heart failure.
• Muscle weakness: Weakness or wasting of muscles, which can be progressive and debilitating.
• Gastroesophageal reflux: A condition where stomach acid flows back up into the esophagus, causing discomfort and pain.

These symptoms can vary in severity and may be accompanied by other complications. It's essential to consult a clinical genetic specialist for an accurate diagnosis and guidance on managing this condition.

References:

• [3] describes infantile onset of acute metabolic acidosis, hypertrophic cardiomyopathy, and muscle weakness associated with deficiency of mitochondrial complex I activity in muscle, liver, and fibroblasts.
• [4] lists clinical features including decreased activity of mitochondrial complex I, hyper-beta-alaninemia, increased circulating lactate concentration, and 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 complex I. Here are some diagnostic tests that may be used to diagnose this condition:

• Sequence analysis: This test involves analyzing the entire coding region of the NDUFS4 gene to identify any mutations or variations that may be causing the deficiency.
• Bi-directional Sanger Sequence Analysis: This is a type of sequence analysis that involves sequencing both strands of DNA to ensure accurate results.
• Genetic testing: This test can confirm a diagnosis and help identify the underlying genetic cause of the condition.

According to [result 11], the Translational Metabolic Laboratory offers bi-directional Sanger Sequence Analysis for Mitochondrial complex I deficiency, nuclear type 1. Similarly, [result 12] mentions that this laboratory also offers sequence analysis for Mitochondrial complex 1 deficiency, nuclear type 21.

It's worth noting that [result 10] suggests that a consultation and evaluation with a clinical genetic specialist is essential to determine the best course of action for diagnosis and testing.

References:

• [Result 11]
• [Result 12]
• [Result 10]

Please note that these references are citations from the search results provided in the context.

Treatment Options for Nuclear Type Mitochondrial Complex I Deficiency

According to available research, there are several treatment options that have been explored for nuclear type mitochondrial complex I deficiency.

• CoQ10 and B vitamins: Coenzyme Q10 (CoQ10) and a B vitamin are commonly used medications in the starting "mitochondrial treatment cocktail" [1].
• Riboflavin, thiamine, biotin, CoQ10, and carnitine: A variety of treatments have been tried, which may or may not be effective, including riboflavin, thiamine, biotin, CoQ10, and carnitine [11].
• Supportive and preventive approaches: Current treatment for primary mitochondrial disease (PMD), which includes nuclear type mitochondrial complex I deficiency, revolves around supportive and preventive approaches [3].

It's essential to note that these treatments may not be effective for everyone, and more research is needed to understand their efficacy. Additionally, the effectiveness of these treatments can vary depending on the individual case.

References:

[1] S Parikh · 2009 · Cited by 404 [11] A variety of treatments, which may or may not be effective, include: riboflavin, thiamine, biotin, CoQ10, and carnitine. [3] Primary mitochondrial disease (PMD) is a group of complex genetic disorders that arise due to pathogenic variants in nuclear or mitochondrial genomes.

Differential Diagnosis of Nuclear Type Mitochondrial Complex I Deficiency

Nuclear type mitochondrial complex I deficiency, specifically type 18, is a rare genetic disorder caused by mutations in the NDUFB11 gene. When considering differential diagnosis for this condition, several other mitochondrial disorders and genetic conditions should be taken into account.

Similar Conditions:

• Mitochondrial Complex I Deficiency: This is the most common enzymatic defect of oxidative phosphorylation disorders, accounting for up to 30% of cases (12). It presents with a wide range of clinical disorders, from lethal neonatal disease to adult-onset neurodegenerative disorders.
• Leigh Syndrome: A severe and progressive neurological disorder caused by mutations in mitochondrial or nuclear genes, leading to impaired oxidative phosphorylation (15).
• MELAS Syndrome: A mitochondrial disorder characterized by encephalomyopathy, lactic acidosis, and stroke-like episodes, often associated with mutations in the MT-TL1 gene (15).

Other Genetic Conditions:

• Hypertrophic Cardiomyopathy: A genetic condition that can be caused by mutations in various genes, including those involved in mitochondrial function (3).
• Mitochondrial Myopathies: A group of disorders characterized by muscle weakness and other symptoms, often associated with mutations in mitochondrial or nuclear genes (2).

Diagnostic Considerations:

When diagnosing nuclear type mitochondrial complex I deficiency, it is essential to consider the clinical presentation, family history, and laboratory findings. This may involve:

• Muscle Biopsy: To assess mitochondrial function and identify enzymatic defects.
• Genetic Testing: To detect mutations in the NDUFB11 gene or other genes associated with mitochondrial disorders.
• Imaging Studies: To evaluate for signs of neurological or muscular involvement.

References:

(2) - A mitochondrial metabolism disease that is characterized by deficiency of cytochrome c oxidase, myopathy, hepatomegaly, hypertrophic cardiomyopathy, lactic acidosis...

(3) - The nuclear mutations can cause hypertrophic cardiomyopathy, hypotonia, lactic acidosis, 3-methylglutaconic acid in urine, hyperammonemia, and epilepsy. CoQ10 ...

(12) - Complex I deficiency is the most frequent mitochondrial disorder presenting in childhood, accounting for up to 30% of cases.

(15) - 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)...