mitochondrial complex V (ATP synthase) deficiency nuclear type 5

Mitochondrial Complex V Deficiency Nuclear Type 5: A Rare Genetic Disorder

Mitochondrial complex V deficiency, also known as ATP synthase deficiency, is a rare genetic disorder that affects the mitochondria's ability to produce energy for the cell. The nuclear type 5 (MC5DN5) variant of this condition is caused by mutations in the ATP5F1D gene on chromosome 19p13.

Key Features:

• Childhood Onset: MC5DN5 typically presents with symptoms during childhood, often accompanied by episodes of metabolic decompensation.
• Lactic Acidosis and Hyperammonemia: This condition is characterized by high levels of lactic acid and ammonia in the blood, which can lead to serious complications if left untreated.
• Mitochondrial Dysfunction: The disorder results from a deficiency in mitochondrial complex V (ATP synthase), leading to impaired energy production within cells.

Causes and Risk Factors:

• Genetic Mutation: MC5DN5 is caused by homozygous mutations in the ATP5F1D gene, which codes for a subunit of mitochondrial complex V.
• Inherited Trait: This condition can be inherited from an affected parent, although it may also occur spontaneously.

Symptoms and Complications:

• Episodic Metabolic Decompensation: MC5DN5 is characterized by recurring episodes of metabolic decompensation, which can lead to serious complications such as lactic acidosis, hyperammonemia, and even death.
• Neurological Symptoms: Some individuals with MC5DN5 may experience neurological symptoms, including seizures, developmental delays, and muscle weakness.

References:

• [1] Sep 13, 2018 - For a general phenotypic description of the nuclear type of mitochondrial complex V deficiency and a discussion of genetic heterogeneity of this condition.
• [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.
• [3] Definition. A mitochondrial disorder characterized by childhood onset of episodic metabolic decompensation featuring lactic acidosis and hyperammonemia accompanied by ...
• [4] Dec 5, 2022 - Nuclear type 5 (MC5DN5) is a disease in which the ATP5F1D gene with 19p13 chromosomal localization is responsible. This metabolic disorder ...

Based on the search results, here are the signs and symptoms associated with mitochondrial complex V (ATP synthase) deficiency, specifically the nuclear type 5:

• Neuropathy: Mitochondrial complex V deficiency can cause a condition called neuropathy, ataxia, and retinitis pigmentosa (NARP), which affects the nervous system [1].
• Cardiac issues: Signs and symptoms of familial dilated cardiomyopathy associated with mitochondrial complex V deficiency include an irregular heartbeat (arrhythmia), shortness of breath (dyspnea), extreme tiredness (fatigue) [2].
• Neurological problems: Decreased activity of mitochondrial ATP synthase complex is associated with various neurological issues, including:
  • Nystagmus
  • 3-Methylglutaconic aciduria
  • Cerebellar hypoplasia
  • Encephalopathy
  • Irritability
  • Seizure [3]

It's worth noting that these symptoms can vary in severity and presentation, and may be influenced by the specific genetic mutation or environmental factors.

References: [1] Context result 1: Nov 1, 2017 [2] Context result 2: Signs and symptoms of familial dilated cardiomyopathy [3] Context result 3: Decreased activity of mitochondrial ATP synthase complex

Diagnostic Tests for Mitochondrial Complex V (ATP Synthase) Deficiency Nuclear Type 5

Mitochond

Current Treatment Options for Mitochondrial Complex V Deficiency

Mitochondrial complex V deficiency, also known as ATP synthase deficiency, is a rare genetic disorder that affects the production of energy in cells. While there is no specific treatment for this condition, various therapeutic approaches have been explored to manage its symptoms.

• Dietary Supplements: Currently, all treatment of mitochondrial disorders, including complex V deficiency, is performed with dietary supplements or off-label use of drugs approved for other indications [2][4].
• Off-Label Use of Drugs: Some medications, such as benzafibrate and resveratrol, have been used to target the master regulator of mitochondrial biogenesis, PGC-1α, which may help alleviate symptoms associated with complex V deficiency [1].
• Supportive Care: The accepted treatment approach for mitochondrial diseases, including complex V deficiency, is supportive care, aimed at managing symptoms and improving quality of life [5].

Emerging Therapies

Recent studies have investigated the potential of various compounds to treat mitochondrial diseases, including complex V deficiency. These emerging therapies include:

• Acipimox: A medication that aims to increase cellular mitochondrial concentration by targeting PGC-1α [9].
• Bezafibrate: A drug that has been shown to improve mitochondrial function and may be beneficial for individuals with complex V deficiency [9].

Important Considerations

It is essential to note that these treatment options are not specific to mitochondrial complex V deficiency nuclear type 5 and may vary depending on individual circumstances. Consultation with a healthcare professional is necessary to determine the most appropriate course of action.

References:

[1] S Avula (2014) - Cited by 120 [2] O Hurko (2013) - Cited by 14 [4] O Hurko (2013) - Cited by 14 [5] Dec 5, 2022 - Cited by unknown [9] RJ Tinker (2021) - Cited by 65

Mitochondrial complex V (ATP synthase) deficiency, nuclear type 5 (MC5DN5), is a rare genetic disorder caused by mutations in the ATP5F1D gene. This condition leads to a decrease in the activity of the mitochondrial ATP synthase complex, resulting in severe metabolic disorders.

The differential diagnosis for MC5DN5 involves considering other conditions that may present with similar symptoms, such as:

• Mitochondrial complex V deficiency nuclear type 4A (MC5DN4A): This is an autosomal dominant metabolic disorder characterized by poor feeding and failure to thrive in infancy [9]. While it shares some similarities with MC5DN5, the inheritance pattern and specific symptoms may differ.
• Mitochondrial complex V deficiency nuclear type 1: This group of defects caused by mutations in nuclear genes leading to a decrease in ATP synthase complex activity may also present with similar symptoms to MC5DN5 [8].
• Other mitochondrial disorders: Conditions such as hypertrophic cardiomyopathy, nystagmus, and encephalopathy may be considered in the differential diagnosis for MC5DN5, particularly if they are caused by mutations in genes involved in mitochondrial function [1].

It's essential to note that a definitive diagnosis of MC5DN5 requires genetic testing to confirm the presence of mutations in the ATP5F1D gene. A thorough medical history, physical examination, and laboratory tests can help rule out other conditions and support a diagnosis of MC5DN5.

References:

[1] Context 2: Decreased activity of mitochondrial ATP synthase complex · Nystagmus · 3-Methylglutaconic aciduria · Cerebellar hypoplasia · Encephalopathy · Irritability · Seizure. [8] Context 8: 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 activity. [9] Context 5 and 9: Mitochondrial complex V deficiency nuclear type 4A (MC5DN4A) is an autosomal dominant metabolic disorder characterized by poor feeding and failure to thrive in infancy.