nuclear type mitochondrial complex I deficiency 16

Nuclear Type Mitochondrial Complex I Deficiency 16 (MC1DN16)

Mitochondrial complex I deficiency, nuclear type 16 is a form of mitochondrial disorder characterized by defective oxidative phosphorylation. It affects approximately 1 in 5-10000 live births and can present with a range of clinical disorders, from neonatal disease to adult-onset neurodegenerative disorders [5].

This condition is caused by homozygous or compound heterozygous mutation in the NDUFAF5 gene on chromosome 20p12.1 [4, 10]. The NDUFAF5 gene plays a crucial role in the function of complex I, which is the first of five mitochondrial complexes involved in oxidative phosphorylation.

The clinical features of MC1DN16 can vary widely and may include:

• Neonatal disease
• Adult-onset neurodegenerative disorders
• Macrocephaly with progressive leukodystrophy
• Nonspecific encephalopathy
• Hypertrophic cardiomyopathy

Dysarthric speech is a common feature in some cases, characterized by poor articulation and further classified into different types depending on the involved neurological structures [14].

MC1DN16 shows extreme genetic heterogeneity and can be caused by mutation in nuclear-encoded genes or in mitochondrial-encoded genes [7]. It is essential to note that this condition is relatively rare compared to other forms of mitochondrial complex I deficiency.

References:

[4] Context result 4 [5] Context result 5 [7] Context result 7 [10] Context result 10 [14] Context result 14

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 breathing, is a common symptom of mitochondrial complex I deficiency (4, 5).
• Encephalopathy: This refers to brain dysfunction or damage that can lead to symptoms such as confusion, seizures, and coma (5).
• Epilepsy: Seizures are a possible symptom of mitochondrial complex I deficiency (5).
• Ataxia: This is a condition characterized by problems with coordination and balance (5).
• Dystonia: This refers to involuntary muscle contractions that can lead to repetitive movements or postures (5).
• Hypotonia: Muscle weakness or low muscle tone is another possible symptom of mitochondrial complex I deficiency (5).
• Myalgia: Muscle pain or aches are also associated with this condition (5).
• Lactic acidosis: This refers to an excessive accumulation of lactic acid in the body, which can lead to symptoms such as fatigue and shortness of breath (4, 6).

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: This test can be used to identify mutations in the NDUFS4 gene, which is associated with mitochondrial complex I deficiency. [1][2]
• Sanger sequencing: This test can also be used to detect mutations in the NDUFS4 gene and other genes associated with mitochondrial complex I deficiency. [3][12]
• Invitae Nuclear Mitochondrial Disorders Panel: This panel analyzes nuclear-encoded genes that are associated with mitochondrial dysfunction, including those related to mitochondrial complex I deficiency. [5]

It's also 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. [10] Additionally, specialists may suggest specific genetic testing or other types of tests to help reach a diagnosis.

References: [1] - Context 3 [2] - Context 12 [3] - Context 5 [5] - Context 6

Differential Diagnosis of Nuclear Type Mitochondrial Complex I Deficiency 16

Mitochondrial complex-I deficiency, nuclear type 16 (MC1DN16), is a rare form of complex-I deficiency caused by biallelic pathogenic variants in the NDUFAF5 gene. The differential diagnosis for MC1DN16 involves considering other mitochondrial disorders that present with similar clinical and biochemical features.

Key Differential Diagnoses:

• Mitochondrial Complex I Deficiency, Nuclear Type 1 (MC1DN1): This is another form of complex-I deficiency caused by mutations in the NDUFS4 gene. While MC1DN16 is more rare, both conditions present with similar clinical features, including hypertrophic cardiomyopathy, hypotonia, and lactic acidosis.
• Mitochondrial Complex III Deficiency: This condition is characterized by decreased activity of complex III and can present with similar biochemical abnormalities as MC1DN16. However, the underlying genetic cause may differ.
• Other Mitochondrial Disorders: Given the heterogeneity of mitochondrial disorders, other conditions such as mitochondrial myopathies, cardiomyopathies, or encephalopathies should also be considered in the differential diagnosis.

Clinical Features to Consider:

When differentiating MC1DN16 from other mitochondrial disorders, clinicians should consider the following clinical features:

• Hypertrophic Cardiomyopathy: A hallmark feature of MC1DN16, which can also be present in other mitochondrial disorders.
• Hypotonia: Muscle weakness or hypotonia is a common feature in many mitochondrial disorders, including MC1DN16.
• Lactic Acidosis: Elevated lactate levels are often seen in mitochondrial disorders, including MC1DN16.

Genetic Testing:

The diagnosis of MC1DN16 relies on genetic testing to identify biallelic pathogenic variants in the NDUFAF5 gene. Other mitochondrial disorders may also require genetic testing for accurate diagnosis.

References:

• [7] Mitochondrial complex-I deficiency, nuclear type 16, is a rare form of complex-I deficiency, caused by biallelic pathogenic variants in NDUFAF5 ...
• [12] In 2 unrelated patients with complex I deficiency nuclear type 1 and decreased activity of complex III, Budde et al. (2000) demonstrated homozygous mutations in the NDUFS4 gene (602694.0002 and 602694.0003). ... Molecular diagnosis in mitochondrial complex I deficiency using exome sequencing. J. Med. Genet. 49: 277-283, 2012.
• [13] Complex I deficiency is the most frequent mitochondrial disorder presenting in childhood, accounting for up to 30% of cases. As with many mitochondrial disorders, complex I deficiency is characterised by marked clinical and genetic heterogeneity, leading to considerable diagnostic challenges for the clinician, not least because of the involvement of two genomes.