MELAS/Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like Episodes
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Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual
diagnosed with MELAS, the following evaluations are
Measurement of height and weight to assess growth
Assessment of cognitive abilities
Physical therapy assessment
Neurologic evaluation, MRI, MRS [Kaufmann et al
2004], and, if seizures are suspected, EEG
Screening for diabetes mellitus by fasting serum glucose
concentration and glucose tolerance test
Medical genetics consultation
Treatment of Manifestations
Sensorineural hearing loss has been successfully treated with
cochlear implantation [Sue et al
1998, Scarpelli et al
Ptosis can benefit from eyelid "crutches," blepharoplasty, or
frontalis muscle-eyelid sling placement.
No therapy is available for PEO or retinopathy.
Aerobic exercise is helpful in MELAS and other mitochondrial
diseases [Taivassalo &
Haller 2004]. Physical therapy should be implemented in
individuals after strokes.
Seizures respond to traditional anticonvulsant therapy.
Standard analgesics can be used for migraine headaches.
Cardiac manifestations can benefit from standard pharmacologic
Diabetes mellitus can be managed by dietary modification only,
especially in thin individuals, or with oral hypoglycemic agents,
but often requires insulin therapy.
L-arginine showed promise in treating stroke-like episodes in
MELAS [Koga et
Prevention of Primary Manifestations
No specific treatment for MELAS exists.
The administration of coenzyme
Q10 (CoQ10) (50-100 mg 3x/day) and
L-carnitine (1000 mg 3x/day) has been of some benefit to some
individuals. In a small randomized double-blind placebo-controlled
study, CoQ10 combined with creatine and lipoic acid
produced modest benefits including slowing progression of ankle
weakness and lower resting plasma lactate concentration [Rodriguez et al
Idebenone, an analog of CoQ10 that crosses the
blood-brain barrier more efficiently, has also been reported as
beneficial in anecdotal reports [Napolitano et al
2000]. A clinical trial of idebenone for MELAS is in progress
[Author, personal observation].
Prevention of Secondary Complications
Because febrile illnesses may trigger acute exacerbations,
individuals with MELAS should receive standard childhood
vaccinations, flu vaccine, and pneumococcal vaccine.
Affected individuals and their at-risk relatives should be
followed at regular intervals to monitor progression and the
appearance of new symptoms. Annual ophthalmologic, cardiologic
(electrocardiogram and echocardiogram), and endocrinologic
evaluations (fasting blood sugar and TSH) are recommended.
Agents/Circumstances to Avoid
Individuals with MELAS should avoid mitochondrial toxins such
as: aminoglycoside antibiotics, linezolid, cigarettes, and alcohol.
Valproic acid should be avoided in the treatment of seizures [Lin & Thajeb
Dichloroacetate (DCA) reduces blood lactate by activating the
pyruvate dehydrogenase complex. Anecdotal reports of effectiveness
have not been substantiated by a double-blind, placebo-controlled
trial, which in fact documented a toxic effect of DCA on peripheral
nerves and concluded that individuals with MELAS (who are already
at increased risk for peripheral neuropathies) should avoid DCA [Kaufmann et al
Evaluation of Relatives at Risk
Molecular genetic testing of at-risk maternal relatives may
reveal individuals who have high mutational loads and are thus at
risk of developing symptoms. However, no proven disease-modifying
intervention exists at present.
Genetic Counseling for issues related to testing of
at-risk relatives for
genetic counseling purposes.
Infertility may preclude pregnancy in some
affected individuals. Women with MELAS should
genetic counseling prior to pregnancy. During pregnancy,
affected or at-risk women should be monitored for diabetes mellitus
and respiratory insufficiency, which may require therapeutic
interventions [Díaz-Lobato et al
Therapies Under Investigation
Oral administration of L-arginine seems to attenuate the
severity of strokes when administered in the acute phase [Koga et al
2005] and to reduce the frequency of strokes when given
interictally [Koga et al
2005, Koga et al
2010]; double-blind studies are needed to confirm these
Beneficial effects of oral succinate were reported in one
individual [Oguro et al
The role of heart transplantation for progressive cardiomyopathy
has been reviewed [Bhati et al
The transfer of nuclear
DNA from fertilized oocytes or zygotes harboring a mtDNA
pathogenic variant to a recipient enucleated recipient cells could
theoretically prevent transmission of mtDNA diseases and proof of
this concept has been demonstrated in pronuclear transfers from
abnormally fertilized zygotes that were allowed to under several
replications in vitro [Craven et al
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diseases and conditions.