MELAS Syndrome


MELAS syndrome is a rare genetic disease which is largely unknown about by many people. This article delves into a topic which has not been researched into such a depth as many other diseases. It looks at the inner workings of this disease as well as how it affects the patient’s life. This disease can often be unrecognized or under diagnosed in a society that is unaware of this condition. MELAS Syndrome particularly affects the brain, muscles and nervous system as a result of mitochondrial mutation[1]


MELAS stands for Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes. It usually results in dementia or strokes for the patient[2] . In this article I will be analyzing the causes of the condition, symptoms, how the condition is diagnosed as well as available treatments. As of now scientists have been unable to find a cure for the disease but I will also present my view on this matter.

Case Study

This is a case that I witnessed while carrying out work experience in the stroke and elderly care ward of a[3] hospital. In a ward where the majority of patients were elderly a 31-year-old Caucasian female was presented after an episode of right-sided weakness. Leading up to this event she had suffered from headaches and 8 episodes of right-sided weakness.
Her background includes sensorineural hearing loss, diabetes, migraines, left ventricular systolic dysfunction, seizures, reduced bowel motility requiring ileostomy and urinary retention.[4]
mage result for sensorineural hearing loss
On examination the cranial nerves seemed to be intact and neurological examination showed a facial droop of the right side and reduced power on the right limbs. Initial blood tests and CT head scan were normal.
Aged 10 years she started having droopy eye lids, migraines and frequent sickness and sinusitis episodes.
When she was 15 years old she had her first stroke-like episode and started developing neuropathic pain and weakness of the muscles in both her legs age 18. The first epileptic presentation was at 24 years and she was diagnosed with moderate left ventricular systolic dysfunction at 25. [5]
igure 6: Systolic and diastolic heart failure. Systolic heart failure: Approximately half of patients with heart failure have left ventricular systolic dysfunction, in which the ability of the left ventricle (LV) to contract and pump blood to the body is reduced. In the normal heart (A), about 50% of the blood in the LV is ejected into the aorta and the body as the chamber contracts; this is known as the ejection fraction. In systolic heart failure (B), changes to the LV (enlargement of the chamber and impaired contractility) mean that a much smaller proportion of the blood in the LV before contraction (typically <40%) is ejected. Systolic heart failure is therefore also known as heart failure with reduced ejection fraction (HF-REF). The total amount of blood leaving the LV in HF-REF may be similar to normal, as the enlarged LV contains more blood than in the normal heart. Diastolic heart failure: Impaired filling of the LV (diastolic dysfunction) is the main factor underlying development of diastolic heart failure (C). Characteristic changes to the heart include thickening of the left ventricular wall and enlargement of the left atrium. The proportion of blood ejected from the LV is normal or near normal although the changes to the LV wall mean that the total volume of blood may be lower than normal and pressure inside the heart may be higher than normal. Diastolic heart failure is also known as heart failure with preserved ejection fraction (HF-PEF). Compared with HF-REF, patients with HF-PEF are generally older, more frequently female, and most have a history of high blood pressure.[15, 75] HF-PEF is becoming more common; however, there are currently few effective treatments for HF-PEF.[76]
At 26 years she suffered from malabsorption and lost 4 stone in 4 months and therefore needed a PEG tube for feeding. As a result of the reduced bowel motility she required an ileostomy aged 28 years.
She has a family history of MELAS Syndrome with her mother, aunt, grandmother and both sisters being affected. Molecular gene testing at the age of 15 showed that she had a m.3243A>G mutation and diagnosis of MELAS syndrome was confirmed.

Causes of MELAS Syndrome

The primary cause of the syndrome is mutations in the mitochondrial DNA[6] . More specifically, it is caused by an A-G point mutation in transfer RNA loop. As it is a genetic condition it is inherited from the mother if she is affected. The stroke like episodes are thought to have been caused by an oxidative phosphorylation (the way enzymes are used within a cell to oxidize nutrients) dysfunction within the brain. [7]
The diagram below shows inheritance pattern: [8]
mage result for melas syndrome dna


The symptoms are usually seen between the ages of 4 and 15 years. The table below shows some of the symptoms typically experienced by people with MELAS Syndrome.[9][10]

Symptoms of MELAS Syndrome
Encephalopathy (sometimes with headaches or seizures)
Abnormal thinking or dementia
Build up of lactic acid within the blood
Stroke like episodes
Local paralysis- arm or leg (temporary)
Hearing loss
Cardiac disease
Stunted growth
Intolerance to exercise due to lack of energy

Diagnosis of the Syndrome

The diagnosis of MELAS Syndrome relies heavily on molecular genetic testing as well as clinical finding. Lactate levels are measured, as these are characteristically higher in a person who has MELAS Syndrome. Imaging of the brain, such as an MRI scan, is used to look for stroke-like lesions. MRI scans are also conducted to find a lactate peak in the brain. An ECG is used to look for the abnormalities of heart rhythm that characterize the syndrome. An echocardiogram is used to look for cardiomyopathy. The muscle biopsy may also show ragged red fibers, which are commonly seen with patients that have MELAS Syndrome. [11][12]
These scans show stroke-like lesions within the brain.
mage result for mri scan melas syndrome


Though there is no cure for MELAS Syndrome there are ways toalleviate the symptoms[13]. Anti-convulsant drugs may be used to prevent and control any seizures the patient may have. However valproic acid must not be given to anyone who suffers from MELAS Syndrome as it causes stroke-like symptoms. The patient may have cochlear implant which are used to treat sensorineural deafness. The doctor may also recommend that they have moderate training using a treadmill. This will improve their overall aerobic capacity as well as reduce the lactate levels at rest. Arginine can be given through an intravenous system to improve stroke-like episodes. Oral Arginine is used to reduce the recurrence of stroke-like episodes.

Investigational therapies to treat MELAS Syndrome
Coenzyme Q10
Ascorbic acid
Creatine Monohydrate

(Scaglia, MELAS Syndrome 2011)

Mortality and Morbidity

MELAS Syndrome has a high mortality and morbidity rate. The stroke-like episodes can be extremely serious and seizures may occur during these episodes as well. Cardiac problems such as cardiomyopathy may result from the syndrome and these are fatal. The patient may also have renal failure as a result of focal segmental glomerulosclerosis. [14]


I believe that we as a society need to do more to make people aware of MELAS Syndrome as possibly millions of cases are going undiagnosed people are unaware of the warning signs. I think acute exacerbations need to be prevented by avoiding mitochondrial toxins such as Linezolid, alcohol, cigarettes and aminoglycoside antibiotics.
I think money should be invested to do further research on SIRT-1 agonists (Sirtuin compounds) in the treatment of mitochondrial diseases like MELAS Syndrome. These agents stimulate peroxisome proliferator-activated receptor (PPAR) family and regulate gene expressions of multiple metabolic pathways.
Sensorineural hearing loss: A type of hearing loss where the problem lies in the inner ear, sensory organ, vestibulocochlear nerve or neural part.
Left ventricular systolic dysfunction: Dilation of the left ventricle and vasoconstriction.
Ileostomy: Small intestine diverted through an opening in the abdomen.
Neuropathic pain: Pain caused by a disease or damage to the nervous system.
PEG (Percutaneous endoscopic gastrostomy): Tube passed through abdominal wall into patient’s stomach to feed the patient.
ECG (Electrocardiogram): Test to check heart’s rhythm and electrical activity.
Cardiomyopathy: Diseases of the heart where the heart chambers’ wall have become stretched, thickened or stiff.
Focal segmental glomerulosclerosis: Progressive form of kidney disease which can cause glomerular diseases in adults.
Acute exacerbations: Sudden worsening of COPD symptoms.

About the Author

Sharon Daniel, 16, UK
Sharon enjoys studying science and maths at school. Her favourite branches of science are biology and chemistry and she hopes to pursue a career in medicine in the future to carry out research in finding cures for rare and genetic diseases. Outside of school she enjoys playing chess for the England chess team as well as playing the piano, violin and guitar.
igure F1

  1. \”MELAS – Genetics Home Reference.\” Accessed September 10, 2017.
  2. \”MELAS Syndrome: Mitochondrial Disease, Symptoms … – MedicineNet.\” Accessed September 10, 2017.
  3. \”Sensorineural Hearing Loss – Causes and treatments –\” Accessed September 10, 2017.
  4. \”Our Location | College of Education Community Clinics – Audiology ….\” Accessed September 10, 2017.
  5. \”MELAS syndrome: Clinical manifestations … – ResearchGate.\” Accessed September 10, 2017.
  6. \”MELAS Syndrome: Mitochondrial Disease, Symptoms, & Life … – RxList.\” Accessed September 10, 2017.
  7. \”MELAS Syndrome – NORD (National Organization for Rare Disorders).\” Accessed September 10, 2017.
  8. \”National Institutes of Health (NIH) | Turning ….\” Accessed September 10, 2017.
  9. \”MELAS Syndrome: Mitochondrial Disease, Symptoms, & Life Expectancy.\” Accessed September 10, 2017.
  10. \”MELAS Syndrome – NORD (National Organization for Rare Disorders).\” Accessed September 10, 2017.
  11. \”MELAS Syndrome – NORD (National Organization for Rare Disorders).\” Accessed September 10, 2017.
  12. \”A Case Report of MELAS Syndrome – Journal of the Korean ….\” Accessed September 10, 2017.
  13. \”MELAS syndrome: Clinical manifestations … – ResearchGate.\” Accessed September 10, 2017.
  14. \”M.E.L.A.S. Syndrome.\” Accessed September 10, 2017.

1 thought on “MELAS Syndrome”

  1. Laura Fisher

    Thank you for your informative article. I am a teacher at a school with a student with MELAS. I wanted to read more about it and this paper was one of the clearest, well summarised articles I have read on the topic. I agree with the points you made.

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