Introduction

Kearns-Sayre syndrome (KSS) is a disease that is a rare disease that typically affects the eyes, heart and other important structures of the body. KSS is defined as a mitochondrial disease because the symptoms of the disease are caused by having mitochondria that are defective. As such, another name for the disease is Kearns-Sayre mitochondrial cytopathy. In KSS, there are 3 defining characteristics. These characteristics are chronic progressive external ophthalmoplegia (CPEO), pigmentary retinopathy and the onset of symptoms before the age of 20 years.^1,4 Both CPEO and pigmentary retinopathy affect the eyes and vision.

Whilst KSS most commonly affects the eyes, other parts of the body could also be involved. You may also experience fatigue as a result of KSS. This is because most of the energy that the cells in your body require comes from the mitochondria. This article will unpack KSS, describing its symptoms as well as how this disease may cause you to experience exhaustion.

Overview of KSS

Pathophysiology

KSS affects between 1 and 3 people out of a 100 000.^2,3 It is caused by defects in the DNA that is found in the mitochondria of affected people. The disease arises randomly due to mutations in the mitochondrial DNA. The mutations that cause KSS arise during the course of the patient’s life and are rarely linked to gene inheritance. Since the mitochondria function as the powerhouse of the cell by producing adenosine triphosphate (ATP), defects in the mitochondria can lead to a vast array of complications, including KSS.^4–6

As such, the organs of the body that use a lot of energy become affected. Skeletal muscles and the heart muscle have a high need for energy that comes from ATP.

Taking a closer look at the hallmark symptoms of KSS

The hallmarks of KSS are CPEO and pigmentary retinopathy. In CPEO, the muscles that control how the eyes move are paralysed. The muscles that control the eyelids are weakened, leading to ptosis. ² Ptosis simply refers to droopy eyelids. In pigmentary retinopathy, the retina of your eyes is damaged. The retina is responsible for detecting light from the environment and sending signals to your brain. This is how we are able to see and also perceive colour. The ptosis caused by CPEO also contributes to vision loss in KSS patients.^4,6

Despite the disease being defined by the appearance of CPEO and pigmentary retinopathy by the age of 20, people with KSS also very commonly experience heart problems, more especially heart block.^4,5,7 Heart block (atrioventricular block) is a condition whereby the signals that control the beating of the heart malfunction, leading to irregular or slower heartbeats.

Other symptoms of KSS

Even though KSS mainly affects the eyes and, in many other instances, the heart, the disease also causes other health problems. The muscles in your face may start to become weak, and you may also experience difficulties with chewing, speaking and swallowing. The neck, shoulder, leg and arm muscles may also be affected. KSS also adversely affects the cerebellum (brain stem), which controls movement. As such, KSS may also affect movement and balance, a condition known as cerebellar ataxia. KSS can also have other effects on your nervous system, leading to hearing loss and other neural issues.^1,3,4,6,7

KSS also has an effect on the endocrine system. The endocrine system ensures that the chemicals (hormones) that are required for various processes in your body are kept in check. Therefore, if you have KSS, you may also suffer from conditions such as diabetes, growth hormone deficiency, adrenal insufficiency and hypogonadotropic hypogonadism ^1,3,4,7

Exhaustion in KSS

There is no direct link between KSS and the exhaustion that is experienced by patients. Owing to the effect of KSS on the endocrine system, a person living with the disease may experience secondary exhaustion or fatigue. Hypoparathyroidism can cause fatigue as well as muscle weakness. Therefore, someone with KSS may easily get exhausted even with minimal physical exertion. Diabetes is one of the symptoms of KSS, and diabetes is also known to cause fatigue. Since KSS also results in a decrease of ATP production in cells, a lack of energy may also be experienced. An unhealthy heart can also lead to feelings of tiredness.^1,6,8

Diagnosis

To diagnose KSS, the triad of CPEO, pigmentary retinopathy and onset before the age of 20 years must be confirmed. CPEO and pigmentary retinopathy can be confirmed by observing eye movements, the eye muscles as well as an examination of the retina. Heart block and its severity may also be observed by conducting an electrocardiogram examination. The cerebrospinal fluid (CSF) may also be withdrawn to examine its protein content. If the protein concentration in the CSF is unusually high (> 100 mg/dL), it may lead to a KSS diagnosis.¹ Examination of muscle tissues and fibres may be conducted to check if their structure is normal. Microscopic examinations may also be used to check if the mitochondria in the muscle tissues are normal. Biochemical studies may also be used to check if the DNA structures in the mitochondria are normal.^4,5

Treatment

KSS is an incurable disease, but there are treatments that may be prescribed by your healthcare provider to help you live with the disease. These include hormone therapy to help with the hormone imbalances that may be due to the endocrine system not functioning properly. You may also receive a pacemaker implant to help with or prevent heart block. A KSS patient may also receive a cochlear implant to help with hearing. Coenzyme Q10 (CoQ10 or ubiquinone) may also be prescribed to help protect your cells from oxidation. CoQ10 can help reduce heart block, improve muscle function and help with neural issues. Folic acid may also be recommended for the CSF.^1,4

Surgeries may also be given to improve your vision. Frontalis sling surgery can be used to correct ptosis. If your vision is blurry, surgery (strabismus surgery) can also be done on your eye muscles.¹

Prognosis

KSS is a progressive disease and lifelong condition, but there are interventions that may be applied to ensure that you live a comfortable life.

Summary

KSS is a lifelong disease that commonly affects the eyes and the heart. It mostly affects the eyes, but very commonly involves the heart as well. Many people who have this disease also suffer from heart block, whereby they experience irregular or slow heartbeat. CPEO and pigmentary retinopathy negatively contribute to vision loss. KSS is caused by mutations in the DNA that is found in the mitochondria of patients. Furthermore, KSS affects the endocrine system. The imbalances in the endocrine system cause hypoparathyroidism and diabetes, which may also impact energy levels to result in fatigue. To diagnose KSS, the triad of defining symptoms and other factors is taken into consideration. There is no cure for the disease, but several therapies are administered to make life comfortable.