nuclear type mitochondrial complex I deficiency 3

Mitochondrial Complex I Deficiency, Nuclear Type 3 (MC1DN3)

Mitochondrial Complex I Deficiency, Nuclear Type 3 (MC1DN3) is a rare genetic disorder caused by mutations in the NDUFS7 gene on chromosome 19p13. This condition affects the functioning of mitochondrial complex I, a crucial enzyme complex involved in energy production within cells.

Inheritance Pattern

MC1DN3 is inherited in an autosomal recessive pattern, meaning that both copies of the gene in each cell have mutations. The parents of an individual with this condition typically carry one copy of the mutated gene but do not show symptoms themselves.

Symptoms and Characteristics

The symptoms of MC1DN3 can vary widely among affected individuals, but they often include:

• Lactic acidosis
• Hypotonia (low muscle tone)
• Hypoglycemia (low blood sugar)
• Failure to thrive
• Encephalopathy (brain dysfunction)
• Delayed psychomotor development

Many patients with MC1DN3 experience severe multisystem disorders, and some may die in early childhood. However, longer survival is possible in some cases.

Diagnosis

A diagnosis of MC1DN3 can be made through genetic testing, which involves analyzing the NDUFS7 gene for mutations. A consultation and evaluation with a clinical genetic specialist are essential to confirm the diagnosis.

References:

• [1] - Mitochondrial complex I deficiency is caused by homozygous or compound heterozygous mutation in the NDUFS7 gene (601825) on chromosome 19p13.
• [4] - Moran et al. (2010) described cellular studies of 6 patients, including 2 sibs, with mitochondrial complex III deficiency due to mutations in the BCS1L gene.
• [5] - Autosomal recessive mitochondrial complex III deficiency is a severe multisystem disorder with onset at birth of lactic acidosis, hypotonia, hypoglycemia, ...
• [11] - Autosomal recessive mitochondrial complex III deficiency is a severe multisystem disorder with onset at birth of lactic acidosis, hypotonia, hypoglycemia, failure to thrive, encephalopathy, and delayed psychomotor development.

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:

• Infantile onset: The condition often presents in infancy, with symptoms such as acute metabolic acidosis, hypertrophic cardiomyopathy, and muscle weakness.
• Muscle weakness: Muscle weakness is a hallmark symptom of mitochondrial complex I deficiency, affecting both skeletal and cardiac muscles.
• Cardiac issues: Cardiac problems, including hypertrophic cardiomyopathy, can occur due to the deficiency in mitochondrial complex I activity.
• Metabolic acidosis: Acute metabolic acidosis is another common symptom, which can lead to various complications if left untreated.

These symptoms are associated with a deficiency of mitochondrial complex I activity in muscle, liver, and fibroblasts, and have a material basis in homozygous or compound heterozygous mutation in the ACAD9 gene [3][4].

References:

[3] Context 3 [4] Context 4

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

• Genetic testing: Genetic tests can help identify mutations in the NDUFS4 gene associated with mitochondrial complex I deficiency. According to search result [2], genetic tests from US and labs around the world are available.
• Muscle biopsy: A muscle biopsy can be performed to measure the enzyme activity of complex I in a muscle sample. This is a classical way to establish a complex I deficiency, as mentioned in search result [7].
• Spectrophotometric measurements: Spectrophotometric measurements can also be used to assess the enzyme activity of complex I in a muscle biopsy or other tissue samples.
• The Invitae Nuclear Mitochondrial Disorders Panel: This panel analyzes nuclear-encoded genes associated with mitochondrial dysfunction, including those related to mitochondrial complex I deficiency. According to search result [5], this panel may be useful for diagnosing nuclear type mitochondrial complex I deficiency.

It's worth noting that a consultation and evaluation with a clinical genetic specialist is recommended to determine the best course of action for diagnosis and testing. Search result [11] suggests that specialists may also suggest specific genetic testing or other types of tests to help reach a diagnosis.

References: [2], [5], [7], [11]

Treatment Options for Nuclear Type Mitochondrial Complex I Deficiency

According to various studies, there are several treatment options available 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, 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 curative but rather supportive and preventive approaches. The effectiveness of these treatments can vary depending on the individual case.

References:

[1] S Parikh · 2009 - CoQ10 and a B vitamin are the most commonly used medications in a starting “mitochondrial treatment cocktail.”

[11] A variety of treatments, which may or may not be effective, include: riboflavin, thiamine, biotin, CoQ10, and carnitine.

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. The differential diagnosis for this condition involves identifying other possible causes of similar symptoms and characteristics.

• Other mitochondrial disorders: Conditions like mitochondrial complex III deficiency, mitochondrial DNA depletion syndrome, and Kearns-Sayre syndrome can present with similar symptoms, such as lactic acidosis, hypotonia, and failure to thrive.
• Metabolic disorders: Rare metabolic conditions, including pyruvate dehydrogenase deficiency and alpha-ketoglutarate dehydrogenase deficiency, can also cause complex I-like symptoms.
• Neurodegenerative diseases: Certain neurodegenerative disorders, such as Leigh syndrome and MERRF (myoclonic epilepsy with ragged-red fibers), may exhibit overlapping clinical features with mitochondrial complex I deficiency.

Key distinguishing factors

To differentiate nuclear type mitochondrial complex I deficiency from other conditions, clinicians should consider the following:

• Genetic testing: Molecular analysis can help identify specific mutations in genes encoding complex I subunits or assembly factors.
• Biochemical assays: Enzymatic studies can confirm the presence of complex I deficiency and distinguish it from other metabolic disorders.
• Clinical presentation: The age of onset, severity of symptoms, and presence of specific clinical features (e.g., lactic acidosis, hypotonia) can help narrow down the differential diagnosis.

References

1. Mitochondrial complex III deficiency is a genetic condition that can affect the brain, kidneys, liver, heart, and skeletal muscles [3].
2. Mitochondrial complex I deficiency shows extreme genetic heterogeneity and can be caused by mutation in nuclear-encoded genes or in mitochondrial-encoded genes [6].
3. Isolated complex I deficiency is a rare inborn error of metabolism due to mutations in nuclear or mitochondrial genes encoding subunits or assembly factors [9].

Citations:

• [1]
• [2][6]
• [3][9]