A brief summary of MELAS

MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) is a condition that effects a lot of parts of the body and different people will have very different symptoms.

MELAS is caused by a problem in the cell’s ability to produce energy. 

Most people will get symptoms between the ages of two and 40 years. Often the symptoms are stroke-like episodes, brain damage (encephalopathy), seizures, loss of thinking, remembering, reasoning (dementia), muscle weakness, inability to exercise, normal early development, headaches that keep happening, vomiting that keeps happening, hearing loss, weakness/numbness/pain in the hands or feet (peripheral neuropathy), learning disability, below average height (short stature).

Symptoms seen in MELAS patients

From a number of research studies by scientists and doctors on MELAS, below are lists of symptoms that have been seen in MELAS patients. Different people will have very different symptoms so you may not necessarily have some or any of the below.

It’s sometimes helpful to know what other people have seen just so there’s less uncertainty about what to expect.

Table 1.

MELAS: First Clinical Symptoms Seen

What % of patients a symptom is seen	Symptom
≥25%	·       Seizures ·       Recurrent headaches ·       Stroke-like episodes ·       Cortical vision loss ·       Muscle weakness ·       Recurrent vomiting ·       Short stature
10%-24%	·       Altered consciousness ·       Loss of mental activity ·       Hearing loss ·       Diabetes mellitus (type 1 or 2)
<10%	·       Developmental delay ·       Fever

Table 2.

MELAS: Additional Clinical Symptoms

What % of patients a symptom is seen	Symptom
≥90%	·       Stroke-like episodes ·       Loss of thinking, remembering, reasoning (dementia) ·       Episodes of seizures (Epilepsy) ·       High levels of lactate in the blood (Lactic acidemia) ·       Ragged red fibers (RRFs) on muscle biopsy
7%-89%	·       One-sided weakness (hemiparesis) ·       Cortical vision loss ·       Recurrent headaches ·       Hearing impairment ·       Muscle weakness
50%-74%	·       Weakness/numbness/pain in the hands or feet (peripheral neuropathy) ·       Learning disability ·       Memory impairment ·       Recurrent vomiting ·       below average height (short stature)
25%-49%	·       Calcium deposits in brain structures (Basal ganglia calcification) ·       Muscle jerks (Myoclonus) ·       Loss of control of bodily movements (Ataxia) ·       Episodic altered consciousness ·       Not walking properly (Gait disturbance) ·       Depression ·       Anxiety ·       Psychotic disorders ·       Diabetes mellitus (type 1 or 2)
<25%	·       Damage to the optic nerve reducing vision (Optic atrophy) ·       Progressive loss in vision (Pigmentary retinopathy) ·       Weakness in eye muscle (Progressive external ophthalmoplegia) ·       Trouble controlling movement according to a child’s age (motor developmental delay) ·       Disease of the heart that makes it harder for the heart ot pump blood to the rest of the body (Cardiomyopathy) ·       Problem with the electrical system that controls your heart’s rate and rhythm (Cardiac conduction abnormalities) ·       Progressive loss in kidney function (Nephropathy) ·       A condition in which the pigment is lost from areas of the skin causing whitish patches (Vitiligo)

 

Some more detailed information on the symptoms:

Symptoms in the brain

·       Stroke-like episodes can cause partially reversible damage to the part of the brain that controls speech and comprehension (aphasia), cortical vision loss, motor weakness, headaches, altered mental status, and seizures with the eventual increase in neurologic deficits.

·       Dementia affects intelligence, language, perception, attention, and memory function.

·       Epilepsy – seizures can occur.

·       Migrainous headaches in the form of reoccurring attacks of severe pulsing headaches with frequent vomiting are typical in people with MELAS and can cause stroke-like episodes. These headache episodes are often more severe during the stroke-like episodes.

·       Hearing impairment due to hearing loss is usually mild, slowly increases, and often happens early on.

·       Weakness/numbness/pain in the hands or feet (peripheral neuropathy) is usually long-lasting and increases over time, occurs bodywide

·       Early psychomotor development is usually normal, although developmental delay can occasionally occur.

·       Psychiatric illnesses including depression, bipolar disorder, anxiety, psychosis, and personality changes can occur in MELAS.

Myopathy will be seen in patients as muscle weakness and exercise intolerance.

Symptoms in the Heart (Cardiac)

·       Both enlarged heart chambers (dilated cardiomyopathy) and thickening of the heart (hypertrophic cardiomyopathy) have been seen. But, the more common is an increased pressure overload of the heart (non-obtrusive concentric hypertrophy).

·       Problems with the heart’s electric impulses including Wolff-Parkinson-White syndrome have been reported occasionally.

Symptoms in the Gut

·       Recurrent or cyclic vomiting is common. Other symptoms include diarrhea, constipation, digestive system doesn’t function properly (gastric dysmotility), intestine is unable to contract (intestinal pseudo-obstruction), reoccurring swelling and redness of the pancreas (pancreatitis), and slow growth and development (failure to thrive)

Symptoms related to glands that make horomones (endocrine manifestations)

·       Diabetes mellitus occurs occasionally, and usually starts at age 38. Diabetes can be type 1 or type 2. Individuals with type 2 diabetes can initially be treated with diet or sulfonylurea, although significant insulin deficiency (insulinopenia) can develop and affected individuals may require insulin therapy

·       Below average height (Short stature). Individuals with MELAS syndrome are typically shorter than their unaffected family members. Growth hormone deficiency has occasionally been reported

·       Underactive thyroid, gonad and parathyroid (hypothyroidism, hypogonadotropic hypogonadism, and hypoparathyroidism) are rare symptoms

Other Symptoms

·       Symptoms in the kidney that may include not absorbing electrolytes (Fanconi proximal tubulopathy), high protein in the urine (proteinuria), and scar tissue in the filtering unit of the kidney (focal segmental glomerulosclerosis)

·       High blood pressure in the blood vessels that supply the lungs (Pulmonary hypertension)

·       Skin conditions that may include white patches on the skin (vitiligo), large red patches of skin in a net pattern (diffuse erythema with reticular pigmentation), and excessive hair growth (hypertrichosis) 

·       Long-lasting low iron (Chronic anemia)

 

What to avoid

Prevention of the first symptoms: Once a person with MELAS has the first stroke-like episode, arginine should be given to reduce the risk of re-occuring stroke-like episodes. A daily dose of 150 to 300 mg/kg/day oral arginine in three divided doses is recommended.

Prevention of complications after the initial symptoms: Because illnesses with fever may trigger an episode, people with MELAS should receive standard childhood vaccinations, flu vaccine, and pneumococcal vaccine.

What to keep an eye on: People with MELAS and their at-risk relatives should go in for routine checkups to keep an eye on symptoms. Annual ophthalmologic, audiology, and cardiologic (electrocardiogram and echocardiogram) evaluations are recommended. Annual urinalysis and fasting blood glucose level are also recommended.

Agents/circumstances to avoid: Mitochondrial toxins, including aminoglycoside antibiotics, linezolid, cigarettes, and alcohol; valproic acid for seizure treatment; metformin because of its propensity to cause lactic acidosis; dichloroacetate (DCA) because of increased risk for weakness/numbness/pain in the hands or feet (peripheral neuropathy).

 

Life expectancy

The disease progresses over years with episodes of stroke-like events causing worsening. The course varies from person to person.

·       The death rate was more than 17-fold higher in people with symptoms compared to relatives with not enough of the DNA change to cause disease (carrier). The average age at death in the MELAS group was 34.5±19 years (range 10.2-81.8 years). Of the deaths, 22% occurred in those younger than 18 years.

·       The estimated overall median survival time based on people with symptoms was 16.9 years from onset of symptoms in the brain.

Care management

Treatment of symptoms: Treatment for MELAS is generally given to prevent, control or relieve symptoms.

During the acute stroke-like episode, arginine within three hours of symptom starting is recommended followed by a similar dosage of arginine as a continuous infusion over 24 hours for the next three to five days.

Coenzyme Q₁₀, L-carnitine, and creatine have been beneficial in some people.

Sensorineural hearing loss has been treated with cochlear implantation; seizures respond to traditional anticonvulsant therapy (although valproic acid should be avoided).

Ptosis, cardiomyopathy, cardiac conduction defects, nephropathy, and migraine headache are treated in the standard manner.

Diabetes mellitus is managed by dietary modification, oral hypoglycemic agents, or insulin therapy.

Exercise intolerance and weakness may respond to aerobic exercise.