mitochondrial complex V (ATP synthase) deficiency nuclear type 3

Mitochondrial Complex V (ATP Synthase) Deficiency, Nuclear Type 3: A Rare Disorder

Mitochondrial complex V (ATP synthase) deficiency, nuclear type 3 (MC5DN3) is a rare autosomal recessive disorder with variable manifestations. This condition affects the mitochondria's ability to produce energy for the cell, leading to a range of symptoms and complications.

Key Features:

• Autosomal Recessive Inheritance: MC5DN3 is inherited in an autosomal recessive pattern, meaning that both parents must be carriers of the mutated gene to pass it on to their children.
• Variable Manifestations: The disorder can manifest differently in each individual, with symptoms ranging from mild to severe. Some common features include:
  • Dysmorphic features (abnormal physical appearance)
  • Psychomotor retardation
  • Hypotonia (low muscle tone)
  • Growth retardation
  • Other systemic complications

Causative Gene: The causative gene for MC5DN3 is the ATP5E gene, localized on chromosome 20q13. This gene plays a crucial role in encoding a subunit of mitochondrial complex V (ATP synthase), which is essential for energy production in cells.

References:

• [1] Mitochondrial complex V deficiency is a shortage (deficiency) of a protein complex called complex V or a loss of its function. [2]
• [3-6] Mitochondrial complex V (ATP synthase) deficiency, nuclear type 3 (MC5DN3) is an autosomal recessive disorder with variable manifestations.
• [7] A mitochondrial disorder with heterogeneous clinical manifestations including dysmorphic features, psychomotor retardation, hypotonia, growth retardation, ...
• [9] In nuclear type 3 (MC5DN3), the causative gene is the ATP5E gene localized on chromosome 20q13. This disease was first described in the ...

Mitochondrial complex V (ATP synthase) deficiency, particularly the nuclear type 3, is a rare genetic disorder that affects the production of energy in cells. The signs and symptoms of this condition can vary in severity and may include:

• Neonatal-onset hypotonia: Affected individuals often present with low muscle tone soon after birth [6].
• Lactic acidosis: Elevated levels of lactic acid in the blood, which can lead to respiratory distress and other complications [7].
• Hyperammonemia: High levels of ammonia in the blood, which can cause seizures, encephalopathy, and other neurological symptoms [7].
• Hypertrophic cardiomyopathy: An enlarged heart muscle that can lead to cardiac problems [6].
• 3-methylglutaconic aciduria: A metabolic disorder characterized by the presence of 3-methylglutaconic acid in the urine [7].

In addition to these specific symptoms, individuals with mitochondrial complex V deficiency may also experience more general signs and symptoms, such as:

• Global developmental delay: Affected children may experience delays in reaching developmental milestones, such as sitting, crawling, or walking [2].
• Poor sucking and feeding difficulties: Infants may have trouble suckling and feeding due to muscle weakness and poor coordination [2].
• Respiratory distress: Difficulty breathing, which can be life-threatening if not treated promptly [1, 6].
• Seizures: Recurring seizures can occur due to the abnormal electrical activity in the brain [3].

It's essential to note that the severity and presentation of mitochondrial complex V deficiency can vary significantly among affected individuals. Some people may experience mild symptoms, while others may have more severe manifestations of the condition.

References: [1] Nov 1, 2017 [2] Affected individuals present soon after birth or in early infancy with hypotonia, respiratory distress, and poor sucking. [3] Decreased activity of mitochondrial ATP synthase complex · Nystagmus · 3-Methylglutaconic aciduria · Cerebellar hypoplasia · Encephalopathy · Irritability · Seizure. [6] A mitochondrial complex deficiency characterized by early neonatal onset of hypotonia, hypetrophic cardiomyopathy and apneic spells within hours after birth ... [7] Most cases present with neonatal-onset hypotonia, lactic acidosis, hyperammonemia, hypertrophic cardiomyopathy, and 3-methylglutaconic aciduria.

Diagnostic Tests for Mitochondrial Complex V (ATP Synthase) Deficiency, Nuclear Type 3

Mitochondrial complex V (ATP synthase) deficiency, nuclear type 3 (MC5DN3) is a genetic disorder that affects the production of ATP in cells. Diagnostic tests are essential to confirm the presence of this condition.

• Genetic Testing: Genetic testing is the primary diagnostic method for MC5DN3. It involves analyzing DNA samples from blood or other tissues to identify mutations in the MT-ATP6 gene, which encodes a subunit of mitochondrial complex V (ATP synthase) [1][2].
• Biochemical Tests: Biochemical tests can also be used to diagnose MC5DN3. These tests measure the activity of mitochondrial enzymes and can help identify abnormalities in ATP production [4].
• Muscle Biopsy: A muscle biopsy may be performed to assess muscle function and identify any abnormalities in mitochondrial structure or function [6].

References

[1] Genetic Testing Registry: Mitochondrial complex V (ATP synthase) deficiency, nuclear type 3. (2017)

[2] Nov 1, 2017 — Mitochondrial complex V deficiency is a shortage (deficiency) of a protein complex called complex V or a loss of its function.

[4] Nov 1, 2017 — • Genetic Testing Registry: Mitochondrial complex V (ATP synthase) deficiency ... • MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR.

[6] Dec 2, 2020 — Mitochondrial complex V (ATP synthase) deficiency, nuclear type 3 ... Kit types for Diagnostic tests. Due to the ... Kit types for Diagnostic tests.

Based on the available information, it appears that there are limited treatment options for mitochondrial complex V (ATP synthase) deficiency, particularly for nuclear type 3.

Currently, all treatment of mitochondrial disorders is performed with dietary supplements or by off-label use of drugs approved for other indications [1]. There is no specific treatment for mitochondrial diseases, and the accepted treatment approach is supportive, aimed at managing symptoms and improving quality of life [5].

However, some studies suggest that certain medications may be beneficial in treating mitochondrial complex V deficiency. For example, bezafibrate has been shown to increase mitochondrial biogenesis and may be a potential treatment strategy [9]. Additionally, nicotinamide riboside (NR), a form of vitamin B3, has been proposed as a promising treatment for mitochondrial diseases due to its ability to boost NAD+ levels [8].

It's essential to note that these findings are based on limited research and more studies are needed to fully understand the effectiveness of these treatments. Furthermore, any medical treatment should be consulted with a healthcare professional.

In terms of specific drug treatment for nuclear type 3 mitochondrial complex V deficiency, there is no clear information available in the provided context. However, it's possible that some of the mentioned medications may be explored as potential therapeutic options.

References: [1] O Hurko (2013) - Cited by 14 [5] Dec 5, 2022 - Currently, there is no specific treatment for mitochondrial diseases... [8] ST Ahmed (2018) - Nicotinamide riboside (NR), a form of vitamin B3 and a natural precursor of NAD+... [9] RJ Tinker (2021) - Bezafibrate is a fibrate drug that increases mitochondrial biogenesis...

Mitochondrial complex V (ATP synthase) deficiency nuclear type 3, also known as MC5DN3, is a rare genetic disorder caused by mutations in the ATP5E gene. The differential diagnosis for this condition involves considering other possible causes of mitochondrial dysfunction and ATP synthase deficiency.

Similar conditions to consider:

• Mitochondrial complex V (ATP synthase) deficiency nuclear type 4A (MC5DN4A): This is an autosomal dominant metabolic disorder that also affects the ATP synthase enzyme, but it has a different genetic cause.
• Other mitochondrial disorders: Conditions such as Kearns-Sayre syndrome, MELAS syndrome, and NARP syndrome can present with similar symptoms to MC5DN3, including muscle weakness, fatigue, and lactic acidosis.

Key distinguishing features:

• Genetic cause: MC5DN3 is caused by mutations in the ATP5E gene, while other mitochondrial disorders may be caused by mutations in different genes or by deletions or rearrangements of mitochondrial DNA.
• Inheritance pattern: MC5DN3 has an autosomal recessive inheritance pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition. Other mitochondrial disorders may have different inheritance patterns.

Clinical features:

• Muscle weakness and fatigue
• Lactic acidosis
• Hypotonia (low muscle tone)
• Failure to thrive in infants
• 3-methylglutaconic aciduria

These clinical features can be similar to those seen in other mitochondrial disorders, making differential diagnosis challenging. However, the genetic cause of MC5DN3 and its autosomal recessive inheritance pattern can help distinguish it from other conditions.

References:

• [5] Dec 5, 2022 — In nuclear type 3 (MC5DN3), the causative gene is the ATP5E gene localized on chromosome 20q13. This disease was first described in ...
• [1] Nov 1, 2017 — When mitochondrial complex V deficiency is caused by a mutation in a gene found in nuclear DNA, it has autosomal recessive inheritance.
• [6] Mitochondrial complex V deficiency nuclear type 4A (MC5DN4A) is an autosomal dominant metabolic disorder characterized by poor feeding and failure to thrive in ...