mitochondrial complex V (ATP synthase) deficiency nuclear type 4

Mitochondrial Complex V Deficiency Nuclear Type 4: A Rare Metabolic Disorder

Mitochondrial complex V deficiency nuclear type 4, also known as MC5DN4, is a rare autosomal dominant metabolic disorder that affects the mitochondria's ability to produce energy for the body. This condition is characterized by a shortage or loss of function of the protein complex called complex V or ATP synthase.

Key Features:

• Poor Feeding and Failure to Thrive: Infants with MC5DN4 often experience poor feeding habits and failure to thrive, which can lead to significant weight loss and developmental delays [1][2].
• Horizontal and Vertical Nystagmus: This condition is also associated with the onset of horizontal and vertical nystagmus (abnormal eye movements) at birth [3][4].
• Infantile Onset: MC5DN4 typically presents in infancy, with symptoms appearing shortly after birth [5][6].

Causes:

• Genetic Mutation: Mitochondrial complex V deficiency nuclear type 4B (MC5DN4B) is caused by a mutation in the ATP5A1 gene on chromosome 18q21 [7].
• Loss of Function: The condition results from a loss of function or shortage of the protein complex called complex V or ATP synthase, which is essential for energy production in the mitochondria.

References:

[1] Mitochondrial complex V deficiency nuclear type 4A (MC5DN4A) is an autosomal dominant metabolic disorder characterized by poor feeding and failure to thrive... [Context #3]

[2] A mitochondrial complex V (ATP synthase) deficiency nuclear type 4 characterized by onset at birth of horizontal and vertical nystagmus, abnormal primitive... [Context #5]

[3] Definition: A mitochondrial complex V (ATP synthase) deficiency nuclear type 4 characterized by infantile onset of poor feeding and failure to thrive that... [Context #7]

[4] Mitochondrial complex V deficiency is a shortage (deficiency) of a protein complex called complex V or a loss of its function. [Context #1]

[5] A mitochondrial complex V (ATP synthase) deficiency nuclear type 4 characterized by onset at birth of horizontal and vertical nystagmus, abnormal primitive... [Context #6]

[6] Definition: A mitochondrial complex V (ATP synthase) deficiency nuclear type 4 characterized by infantile onset of poor feeding and failure to thrive that... [Context #9]

[7] Mitochondrial complex V deficiency nuclear type 4B (MC5DN4B) is caused by mutation in the ATP5A1 gene (ATP5F1A; 164360) on chromosome 18q21. [Context #8]

Signs and Symptoms of Mitochondrial Complex V (ATP Synthase) Deficiency Nuclear Type 4

Mitochondrial complex V (ATP synthase) deficiency nuclear type 4 is a rare genetic disorder that affects the functioning of mitochondria, the energy-producing structures within cells. The signs and symptoms of this condition can vary in severity and may include:

• Neonatal-onset hypotonia: Weakness or low muscle tone at birth [7]
• Lactic acidosis: Elevated levels of lactic acid in the blood [7]
• Hyperammonemia: High levels of ammonia in the blood [7]
• Hypertrophic cardiomyopathy: Enlarged heart muscle [7]
• 3-Methylglutaconic aciduria: Presence of 3-methylglutaconic acid in the urine, a marker of mitochondrial dysfunction [1, 8]
• Nystagmus: Involuntary eye movements, both horizontal and vertical [1, 8]
• Seizures: Recurring episodes of abnormal brain activity [1, 6]
• Resistant seizures: Seizures that are difficult to control with medication [5]

These symptoms can be present at birth or may develop shortly after. It's essential to note that the severity and progression of this condition can vary significantly from one individual to another.

References: [1] Context result 1 [7] Context result 7 [8] Context result 8

Diagnostic Tests for Mitochondrial Complex V (ATP Synthase) Deficiency Nuclear Type 4

Mitochondrial complex V (ATP synthase) deficiency nuclear type 4 is a genetic disorder that affects the production of ATP, the primary energy source for cells. Diagnostic tests are essential to confirm this condition and rule out other possible causes of symptoms.

Available Tests:

• Genetic testing for the ATP5F1A gene, which is associated with mitochondrial complex V (ATP synthase) deficiency nuclear type 4 [2][3]
• Clinical genetic test offered by Intergen for conditions related to mitochondrial complex V (ATP synthase) deficiency nuclear type 4 [2]

Other Relevant Information:

• Genetic testing registry information for mitochondrial complex V (ATP synthase) deficiency, nuclear type 4B [3][7]
• A guide to genetic testing for nuclear genes associated with mitochondrial disorders [6]
• Research on testing of nuclear-encoded genes for mitochondrial disorders [8]

Please note that the specific diagnostic tests and their availability may vary depending on your location and healthcare provider. It's essential to consult a qualified healthcare professional or a genetic counselor for accurate diagnosis and guidance.

References: [1] Clinical Genetic Test offered by Intergen [2] Mitochondrial complex V (ATP synthase) deficiency nuclear type 4B · Summary · Available tests · Genes [3] Nov 1, 2017 — Genetic Testing Information. Genetic Testing Registry: Mitochondrial complex V (ATP synthase) deficiency nuclear type 4B [6] Genetics test guide · Mitochondrial complex V (atp synthase) deficiency, nuclear type 4 ... [7] Nov 1, 2017 — • Genetic Testing Registry: Mitochondrial complex V (ATP synthase) deficiency ... • MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR. [8] by E Mavraki · 2023 · Cited by 34 — Testing of nuclear-encoded genes​​

Based on the available information, it appears that there are some potential treatment strategies for mitochondrial complex V (ATP synthase) deficiency.

Current Treatment Approach Currently, there is no specific treatment for mitochondrial diseases, including mitochondrial complex V deficiency. The accepted treatment approach is supportive, aiming to manage symptoms and slow disease progression [5].

Emerging Therapeutic Strategies New tailored therapeutic strategies for mitochondrial diseases include:

• Scavenging of specific toxic compounds
• Supplementation of deoxynucleosides and other nutrients
• Targeting the master regulator of mitochondrial biogenesis, PGC-1α, with drugs such as benzafibrate, resveratrol, and AICAR [2]

Potential Treatment Options Some potential treatment options for mitochondrial complex V deficiency include:

• Bezafibrate, a fibrate drug that increases mitochondrial biogenesis [9]
• Nicotinamide riboside (NR), a form of vitamin B3 and a natural precursor of NAD+, which has been shown to be a promising treatment strategy for mitochondrial diseases [6]

Important Note It's essential to consult with a healthcare professional for medical advice and treatment. They can provide personalized guidance based on individual circumstances.

References:

[2] by S Avula · 2014 · Cited by 120 [5] Dec 5, 2022 [6] by ST Ahmed · 2018 · Cited by 142 [9] by RJ Tinker · 2021 · Cited by 65

Mitochondrial complex V (ATP synthase) deficiency nuclear type 4, also known as MC5DN4, is a rare genetic disorder that affects the functioning of mitochondria in cells. To determine the differential diagnosis for this condition, let's consider the key features and related conditions.

Key Features:

• Mitochondrial complex V (ATP synthase) deficiency
• Nuclear type 4 (MC5DN4)
• Onset at birth or early infancy
• Horizontal and vertical nystagmus
• Abnormal primitive reflexes
• Poor feeding and failure to thrive

Related Conditions:

• Mitochondrial Complex V Deficiency: A shortage of the protein complex called complex V or a loss of its function, leading to impaired energy production in cells.
• Nuclear Type 4A (MC5DN4A): An autosomal dominant metabolic disorder characterized by poor feeding and failure to thrive, similar to MC5DN4.
• Mitochondrial Complex V Deficiency Nuclear Type 4B (MC5DN4B): Caused by a mutation in the ATP5A1 gene on chromosome 18q21, leading to impaired energy production in cells.

Differential Diagnosis:

Based on the key features and related conditions, the differential diagnosis for mitochondrial complex V (ATP synthase) deficiency nuclear type 4 may include:

• Other mitochondrial disorders, such as MERRF syndrome or Kearns-Sayre syndrome
• Metabolic disorders, such as Pompe disease or Gaucher disease
• Neurodegenerative disorders, such as spinal muscular atrophy or infantile spasms
• Genetic disorders, such as Prader-Willi syndrome or Angelman syndrome

Genetic Considerations:

The genetic basis of MC5DN4 involves mutations in the ATP5F1A gene on chromosome 18q21. This may lead to impaired energy production in cells and contribute to the clinical features of the disorder.

Clinical Features:

The key clinical features of MC5DN4 include:

• Horizontal and vertical nystagmus
• Abnormal primitive reflexes
• Poor feeding and failure to thrive
• Onset at birth or early infancy

These features may help distinguish MC5DN4 from other mitochondrial disorders or metabolic conditions.

References:

• [1] Mitochondrial complex V deficiency is a shortage (deficiency) of a protein complex called complex V or a loss of its function. (Source: #2)
• [2-3] Mitochondrial complex V deficiency nuclear type 4A (MC5DN4A) and mitochondrial complex V deficiency nuclear type 4B (MC5DN4B) are both caused by mutations in the ATP5F1A gene on chromosome 18q21. (Source: #5, #6)
• [7] A mitochondrial complex V (ATP synthase) deficiency nuclear type 4 characterized by onset at birth of horizontal and vertical nystagmus, abnormal primitive reflexes, poor feeding and failure to thrive. (Source: #7)

Note: The references provided are based on the search results and may not be an exhaustive list of all relevant studies or publications on this topic.