What is Mitochondrial (mt) disease?

From the Guidelines

Mitochondrial cell diseases are genetic disorders that require a multidisciplinary approach for management, focusing on symptom management and supportive care, as there is no cure currently available. The primary goal of treatment is to preserve mitochondrial function and energy production, as mitochondrial diseases result from mutations in either mitochondrial DNA or nuclear DNA that disrupt the organelles' ability to produce adequate ATP, leading to cellular dysfunction particularly in high-energy demanding tissues like muscles and nerves 1.

Key Recommendations

• Patients should take a combination of supplements including Coenzyme Q10 (100-600 mg daily), L-carnitine (1-3 g daily), riboflavin (100-400 mg daily), and creatine (5-10 g daily) to support mitochondrial function.
• A ketogenic or modified Mediterranean diet may benefit some patients by providing alternative energy sources for affected cells.
• Regular, moderate exercise is recommended to improve mitochondrial function, but should be tailored to the individual's capabilities to avoid overexertion.
• Patients should avoid medications known to impair mitochondrial function, including certain antibiotics (like aminoglycosides), statins, and valproic acid.

Management Considerations

• Meticulous individual assessment is important due to the diverse nature of mitochondrial disease, and careful attention to fluid management is essential, particularly during surgical procedures and perioperative fasting 1.
• Preoperative fasting may be hazardous, and the routine use of lactate-free i.v. fluids is recommended to maintain normoglycaemia and prevent lactic acidosis.
• Genetic counseling is also an important aspect of care for the family of a child with mitochondrial disease, considering the complexity of mitochondrial DNA inheritance and the potential for variable expression and reduced penetrance within families 1.

Diagnostic Considerations

• Mitochondrial disorders can affect any part of the body, with organs having a high energy requirement being particularly vulnerable, and should be suspected in cases of unexplained constellations of signs with a progressive course involving seemingly unrelated organs or tissues 1.
• The interpretation of sequence variants in mitochondrial DNA requires caution, considering factors such as heteroplasmy, homoplasmy, and the tissue-specific expression of mitochondrial variants 1.

From the Research

Diagnosis of Mitochondrial Cell Disease

• Mitochondrial dysfunction should be considered in the differential diagnosis of any progressive multisystem disorder 2
• The diagnosis is most challenging when only one symptom is present, but easier to consider when two or more seemingly unrelated symptoms are present, involving more than one organ system 2
• A full mitochondrial evaluation is often warranted in children with a complex neurologic picture or a single neurologic symptom and other system involvement 2

Management and Treatment of Mitochondrial Cell Disease

• Consensus-based recommendations are provided for the routine care and management of patients with primary genetic mitochondrial disease 3
• Consensus-based recommendations are provided for the diagnosis and treatment of mitochondrial disease 4
• Current treatment for primary mitochondrial disease revolves around supportive and preventive approaches, with few disease-specific therapies available 5
• However, over the last decade there has been considerable progress in our understanding of both the genetics and pathophysiology of primary mitochondrial disease, resulting in the development of new pharmacological and non-pharmacological therapies 5

Specific Treatable Mitochondrial Disorders

• Coenzyme Q(10) (CoQ(10)) deficiencies and mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) are two examples of treatable mitochondrial disorders 6
• Primary CoQ(10) deficiencies often improve with CoQ(10) supplementation 6
• Allogeneic hematopoetic stem cell transplantation to restore thymidine phosphorylase activity and eliminate toxic metabolites is a promising therapy for MNGIE 6