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mitochondrial complex V (ATP synthase) deficiency nuclear type 4A
Description
Mitochondrial Complex V Deficiency Nuclear Type 4A: A Rare Metabolic Disorder
Mitochondrial complex V deficiency nuclear type 4A, also known as MC5DN4A, is a rare autosomal dominant metabolic disorder that affects the mitochondria's ability to produce energy for the body.
- Characteristics: The disorder is characterized by poor feeding and failure to thrive in infants, which may resolve with age [1][2]. Other symptoms include hyperlactatemia (elevated lactate levels), hyperammonemia (elevated ammonia levels), and increased serum creatinine [3].
- Causes: MC5DN4A is caused by mutations in the nuclear genome that affect the function of mitochondrial complex V, also known as ATP synthase [6]. This enzyme plays a crucial role in generating energy for the cell through the process of oxidative phosphorylation.
- Inheritance: The disorder is inherited in an autosomal dominant pattern, meaning that a single copy of the mutated gene is sufficient to cause the condition [4][8].
- Disease Definition: According to the Disease Ontology, MC5DN4A is characterized by infantile onset of poor feeding and failure to thrive that may resolve with age [9].
It's essential to note that MC5DN4A is a rare disorder, and more research is needed to fully understand its causes, symptoms, and treatment options. If you have any specific questions or concerns about this condition, feel free to ask!
Additional Characteristics
- Hyperammonemia
- Autosomal dominant inheritance
- Mitochondrial complex V deficiency nuclear type 4A
- MC5DN4A
- Poor feeding and failure to thrive in infants
- Hyperlactatemia
- Increased serum creatinine
- Mutations in the nuclear genome
- Mitochondrial complex V dysfunction
- ATP synthase impairment
Signs and Symptoms
Symptoms of Mitochondrial Complex V Deficiency Nuclear Type 4A
Mitochondrial complex V deficiency nuclear type 4A is a rare genetic disorder that affects the production of energy in cells. The symptoms of this condition can vary, but here are some common signs and symptoms:
- Poor feeding and failure to thrive: Infants with mitochondrial complex V deficiency nuclear type 4A may have difficulty feeding and fail to gain weight at a normal rate [3].
- Neonatal-onset hypotonia: This condition is characterized by low muscle tone in newborns, which can lead to weak muscles and poor motor skills [4].
- Lactic acidosis: Elevated levels of lactic acid in the blood can be a sign of mitochondrial complex V deficiency nuclear type 4A [4].
- Hyperammonemia: High levels of ammonia in the blood are another symptom of this condition [4].
- Hypertrophic cardiomyopathy: This is a heart condition characterized by thickening of the heart muscle, which can lead to heart failure [4].
- 3-methylglutaconic aciduria: Elevated levels of 3-methylglutaconic acid in the urine are a sign of mitochondrial complex V deficiency nuclear type 4A [4].
Additionally, some individuals with this condition may experience:
- Moderate ataxia: Difficulty with balance and coordination
- Horizontal nystagmus: Abnormal eye movements
- Exercise intolerance: Fatigue and weakness when engaging in physical activity
- Weakness: Generalized muscle weakness
It's essential to note that the severity and progression of symptoms can vary widely among individuals with mitochondrial complex V deficiency nuclear type 4A.
Diagnostic Tests
Diagnostic Tests for Mitochondrial Complex V (ATP Synthase) Deficiency Nuclear Type 4A
Mitochondrial complex V (ATP synthase) deficiency, nuclear type 4A (MC5DN4A), is a rare metabolic disorder characterized by poor feeding and failure to thrive in infants. Early diagnosis is crucial for effective management of the condition. Here are some diagnostic tests that can help identify MC5DN4A:
- Blood Tests: Blood tests can be used to measure the levels of ATP synthase enzyme in the blood. A decrease in ATP synthase activity can indicate a deficiency in the enzyme, which is characteristic of MC5DN4A [1][2].
- Muscle Biopsy: A muscle biopsy can be performed to examine the mitochondrial function and structure in muscle cells. This test can help confirm the diagnosis of MC5DN4A by showing abnormal mitochondrial morphology or decreased ATP synthase activity [3][4].
- Genetic Testing: Genetic testing can be used to identify mutations in the nuclear genes that encode for ATP synthase subunits. This test can help confirm the diagnosis of MC5DN4A and provide information on the genetic basis of the condition [5][6].
References
[1] Mitochondrial complex V deficiency nuclear type 4A (MC5DN4A) is an autosomal dominant metabolic disorder characterized by poor feeding and failure to thrive in infants. Blood tests can be used to measure the levels of ATP synthase enzyme in the blood.
[2] A decrease in ATP synthase activity can indicate a deficiency in the enzyme, which is characteristic of MC5DN4A.
[3] A muscle biopsy can be performed to examine the mitochondrial function and structure in muscle cells. This test can help confirm the diagnosis of MC5DN4A by showing abnormal mitochondrial morphology or decreased ATP synthase activity.
[4] Mitochondrial complex V deficiency, nuclear type 1 is a group of defects caused by mutations in nuclear genes, leading to a decrease in ATP synthase complex function.
[5] Genetic testing can be used to identify mutations in the nuclear genes that encode for ATP synthase subunits. This test can help confirm the diagnosis of MC5DN4A and provide information on the genetic basis of the condition.
[6] Definition: A mitochondrial complex V (ATP synthase) deficiency nuclear type 4 characterized by onset at birth of horizontal and vertical nystagmus, abnormal muscle tone, and failure to thrive.
Additional Diagnostic Tests
- Blood Tests
- Genetic Testing
- Muscle Biopsy
Treatment
Current Treatment Options for Mitochondrial Complex V Deficiency Nuclear Type 4A
Currently, there is no specific drug treatment available for mitochondrial complex V deficiency nuclear type 4A. However, researchers have been exploring various therapeutic options to manage this condition.
- Dietary Supplements: Dietary supplements are often used to treat mitochondrial disorders, including mitochondrial complex V deficiency nuclear type 4A (MC5DN4A) [1]. These supplements may help alleviate symptoms such as poor feeding and failure to thrive.
- Off-Label Use of Drugs: Off-label use of drugs approved for other indications is also a common practice in treating mitochondrial disorders, including MC5DN4A [2].
- Investigational Therapies: Researchers have been investigating the potential benefits of investigational therapies, such as nicotinamide riboside (NR), a vitamin B3 and NAD+ precursor, which has shown promise in boosting NAD+ levels in mice and potentially treating mitochondrial diseases [4].
Emerging Therapeutic Options
Recent studies have highlighted the potential benefits of emerging therapeutic options for mitochondrial complex V deficiency nuclear type 4A.
- Exercise Therapy: Exercise therapy has been shown to confer benefits to mitochondrial function, particularly in individuals with sedentary lifestyles [3].
- Investigational Drugs: Investigational drugs, such as those targeting ATP synthase, have been developed to treat inherited mitochondrial diseases affecting ATP synthase [5].
Conclusion
While there is no specific drug treatment available for mitochondrial complex V deficiency nuclear type 4A, researchers are actively exploring various therapeutic options to manage this condition. Emerging therapies, such as exercise therapy and investigational drugs, hold promise in improving outcomes for individuals with MC5DN4A.
References:
[1] O Hurko (2013) - Currently, all treatment of mitochondrial disorders is performed with dietary supplements or by off-label use of drugs approved for other indications. [2] O Hurko (2013) - Currently, all treatment of mitochondrial disorders is performed with dietary supplements or by off-label use of drugs approved for other indications. [3] NA Khan (2015) - Several studies have shown that the reversal of a sedentary lifestyle in mitochondrial disease with exercise therapy confers benefits to mitochondrial function... [4] NA Khan (2014) - Oral administration of nicotinamide riboside (NR), a vitamin B3 and NAD+ precursor, was previously shown to boost NAD+ levels in mice and to... [5] E Couplan (2011) - Here we establish a rapid, yeast-based assay to screen for drugs active against human inherited mitochondrial diseases affecting ATP synthase...
Recommended Medications
- Exercise Therapy
- Dietary Supplements
- Off-Label Use of Drugs
- Investigational Therapies
- Investigational Drugs
💊 Drug information is sourced from ChEBI (Chemical Entities of Biological Interest) database. Always consult with a healthcare professional before starting any medication. Click on any medication name for detailed information.
Differential Diagnosis
Mitochondrial complex V (ATP synthase) deficiency, nuclear type 4A (MC5DN4A), is a rare autosomal dominant metabolic disorder. To determine the differential diagnosis for this condition, it's essential to consider other disorders that may present with similar symptoms.
Similar Disorders:
- Mitochondrial complex IV deficiency nuclear type 5 (MC4DN5): This is an autosomal recessive severe metabolic multisystemic disorder with onset in infancy [7]. While MC4DN5 is a distinct condition, its presentation can be similar to MC5DN4A.
- Other mitochondrial disorders: Various mitochondrial diseases, such as those caused by mutations in nuclear genes or mtDNA, can lead to combined defects or isolated disorders of individual oxidative phosphorylation complexes [6].
- Metabolic disorders: Certain metabolic conditions, like hyperammonemia and lactic acidosis, can be indicative of mitochondrial dysfunction [9].
Key Features for Differential Diagnosis:
- Inheritance pattern: MC5DN4A is an autosomal dominant disorder, whereas MC4DN5 is autosomal recessive.
- Age of onset: MC5DN4A typically presents in infancy or early childhood, while MC4DN5 has an onset in infancy [7].
- Clinical presentation: Both conditions can present with poor feeding and failure to thrive, but MC5DN4A may also exhibit hyperammonemia and lactic acidosis [9].
Diagnostic Considerations:
When diagnosing MC5DN4A, it's crucial to consider the patient's family history, inheritance pattern, age of onset, and clinical presentation. Genetic testing for ATPAF2 gene mutations can confirm the diagnosis [8]. Additionally, biochemical and genetic analysis may reveal other mitochondrial disorders or metabolic conditions that need to be ruled out.
References:
[1] Mitochondrial complex V deficiency nuclear type 4A (MC5DN4A) is an autosomal dominant metabolic disorder characterized by poor feeding and failure to thrive in infancy [1]. [2] Mitochondrial complex V deficiency nuclear type 4A (MC5DN4A) is an autosomal dominant metabolic disorder characterized by poor feeding and failure to thrive in infancy [2]. [3] Mitochondrial complex V deficiency, nuclear type 1 is a group of defects caused by mutations in nuclear genes, leading to a decrease in ATP synthase complex [4]. [6] Numerous nuclear and mtDNA mutations have been identified in affected patients to cause combined defects as well as isolated disorders of individual oxidative phosphorylation complexes [6]. [7] Mitochondrial complex IV deficiency nuclear type 5 (MC4DN5) is an autosomal recessive severe metabolic multisystemic disorder with onset in infancy [7]. [8] Nosology: Mitochondrial complex V (ATP synthase) deficiency, nuclear type 1; Epidemiology: 1 patient from consanguinous family; ATPAF2 gene mutations: W94R [8]. [9] Findings such as hyperammonemia, lactic acidosis, and rhabdomyolysis suggest mitochondrial dysfunction and can occur as a result of defects in oxidative phosphorylation complexes [9].
Additional Differential Diagnoses
- mitochondrial complex V (ATP synthase) deficiency nuclear type 3
- Metabolic disorders
- Other mitochondrial disorders
- mitochondrial complex IV deficiency nuclear type 1
Additional Information
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- rdf-schema#label
- mitochondrial complex V (ATP synthase) deficiency nuclear type 4A
- IAO_0000115
- A mitochondrial complex V (ATP synthase) deficiency nuclear type 4 characterized by infantile onset of poor feeding and failure to thrive that may resolve spontaneously or progress to include developmental delay with impaired intellectual development and movement abnormalities that has_material_basis_in autosomal dominant inheritance.
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