Introduction

A variety of rare diseases affect people of different ages, each of which has its own characteristics which may be common. Kearns–Sayre syndrome (KSS) is a mitochondrial DNA deletion syndrome that affects multiple systems of the body. It affects an estimated 1.6 out of 100,000 with an equal sex incidence, starting 20 years prior to age. It is characterised by the following symptoms:^1,2

• Chronic Progressive External Ophthalmoplegia (CPEO)
• Retinitis Pigmentosa (RP)

Symptoms may develop into:

• Cardiac conduction disorders
• Ataxia
• Increasing cerebrospinal fluid protein level greater than 100 mg/dL

Mitochondria are an important organelle found in all nucleated mammalian cells. It is responsible for providing the energy required for cell function by oxidative phosphorylation (OXPHOS). Deletion of mtDNA leads to a change in the function of mitochondria.³ Coenzyme Q10 (CoQ10),(ubiquinone), is an endogenously synthesised vital molecule, found in many unicellular and pluricellular organisms, the latter being mostly localised in the mitochondria. It has a major role in supplying all cells with energy. Biosynthesis begins with the formation of a 4-hydroxybenzoic acid (4-HB) head group and a lipophilic polyisoprenoid tail. This formation occurs in the presence of CoQ 10 in the mitochondrial respiratory chain. CoQ 10 has properties as a mobile electron carrier in the mitochondrial respiratory chain, as well as being a molecule with redox capabilities.⁴ This article provides an overview of the effectiveness of coenzyme Q10 in kearns-sayre syndrome by assessing its function in mitochondria.

Pathophysiology of kearns-sayre syndrome

The KSS is characterised by functional changes including:^1,2,5

Mitochondrial DNA mutations

• Changes in mtDNA are mainly presented as a deletion of a 4.9 kb “common deletion” range from nucleotide positions 8,470 to 13,446. His deletion contains many important functional genes, such as  MT-ATP8
• The abnormalities that happen in mitochondrial DNA (mtDNA) lead to a dysfunction of the mitochondrial respiratory chain

Effect on the cellular energy production

• ATP synthesis defect
• Increased oxidative stress

Clinical symptoms associated with mitochondrial dysfunction

• Cardiac Complications
• Endocrine Disorders
• Dysphagia
• Ptosis
• Muscle weakness
• Fatigue
• Hearing loss

Coenzyme Q10 and mitochondrial bioenergetics⁶  

The main function of CoQ10

• CoQ10 shuttles electrons from complexes I and II to complex III of the mitochondrial respiratory chain
• Plays an antioxidant role to protect cell membranes and circulating lipoproteins from oxidative damage by free radicals (ROS)

The effect of CoQ10 in mitochondrial disorders

• The insufficiency of  CoQ10 is linked with the mitochondrial diseases group, which is a rare disease of hereditary nature. The first case was reported in 1989, where a muscle CoQ10 deficiency was seen in a family with mitochondrial encephalomyopathy. Defects were only detected in complex I + III (NADH-cytochrome c reductase) and II + III (succinate-cytochrome c reductase) activities. These biochemical analyses (of CoQ10 levels in muscle, CI + III, and CII + III activities) became the gold standard of the clinical diagnosis of CoQ10 deficiency
• Additionally, there are two types of CoQ10 deficiency. he primary type results directly from mutations in genes involved in CoQ10 biosynthesis with highly diverse manifestations affecting: the central and peripheral nervous system, the kidneys, the heart, and skeletal muscle. However, the secondary type (more common) remains unrelated to gene mutations. Secondary CoQ10 is accompanied by OXPHOS defects, impaired other non-OXPHOS mitochondrial processes, or a defect in non-mitochondrial functions.  Patients with secondary deficiency exhibit myopathies with muscular weakness, hypotonia, exercise intolerance, or myoglobinuria, which are frequently associated with CoQ10 secondary deficiency type

Therapeutic potential of CoQ10 in KSS⁷

When a patient suffering from KS syndrome was treated with CoQ10 supplement,  improvement in lactate/pyruvate metabolism, cardiac function and eye movement was seen (according to  Ogashara and colleagues in 1985).  A number of studies have assessed the therapeutic potential of CoQ10 in the treatment of MRC disorders with varying clinical outcomes. Improvements in the following were also seen: neurological function, tremor and ataxia; exercise intolerance, cramps and muscle stiffness as well as a minor positive effect on cycle exercise capacity in patients with MRC disorders. Respiratory function in a patient with Kearns-Sayre/chronic external ophthalmoplegia plus syndrome is also promoted.

Nevertheless, the default to evoke clinical or biochemical development in response to CoQ10 supplementation in patients with MRC disorders may be the result of the duration of the treatment or the dosage of CoQ10 employed. 

Challenges and considerations

Bioavailability of CoQ10⁸

There are two forms that  CoQ10 exists within the body in the oxidised form (ubiquinone) and the reduced form (ubiquinol). The manufacturing of  CoQ10 supplements claims that the reduced form of CoQ10 is most readily absorbed from the gastrointestinal tract.

The duration of treatment with CoQ10⁹

• Importance of early intervention

Long-term effects and sustainability (attain a therapeutic blood level of > 2.5 mcg/mL )

Safety and side effects¹⁰

• No serious side effects of CoQ10 have been reported. Mild side effects such as insomnia, digestive upsets, diarrhoea and rash may occur. However, it remains unsafe for children and pregnant or nursing women.CoQ10 can interact with anticoagulants like warfarin and insulin.t may not be compatible with certain types of cancer treatment

Conclusion

The use of CoQ10 for treating  KS syndrome showed improvement in symptoms such as cardiac function, eye movement,  neurological function and promoted respiratory function. However, there is still a need for more randomised controlled trials to determine the efficacy and the optimal dosage of CoQ10. In addition to checking the effectiveness of the supplement on a wide range of patients. Besides improving the quality of life and functional outcomes in affected individuals.