Clinical Pearls & Morning Reports
Published April 26, 2017
Multisystem mitochondrial disorders that cause encephalomyopathy include the Leigh syndrome, MERRF (myoclonic epilepsy with ragged-red fibers), the Kearns–Sayre syndrome, mitochondrial neurogastrointestinal encephalopathy, and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes). Read the latest Case Record of the Massachusetts General Hospital.
Q. What is MELAS?
A. MELAS is one of the most common mitochondrial diseases caused by a mutation in the mitochondrial DNA, with an estimated prevalence of 8 to 236 cases per 100,000 persons. It affects both children and adults and is characterized by multiorgan involvement. MELAS is a polygenic disorder caused by at least 32 mutations in the mitochondrial DNA that affect different mitochondrial genes.
Q. How is MELAS diagnosed?
A. For patients to receive a diagnosis of MELAS, they must have all the symptoms listed in the acronym, including strokes or strokelike episodes. The most common mutation is m.3243AàG in the MT-TL1 gene, which encodes transfer RNA Leu(UUR). Analysis of tissue samples obtained from the most affected parts of the body provides the highest yield for uncovering mutations in the mitochondrial DNA. Saliva, urine, and muscle samples and buccal swabs may be used for genetic testing for MELAS; blood has the lowest yield because of negative selection and high cell turnover.
A: The disease course includes episodes of temporary worsening that are triggered by stressors (e.g., infections, fever, dehydration, overexertion, and even emotional distress). Approximately 40% of patients with MELAS have strokelike episodes by the time they are 40 years of age, with a lifetime prevalence of stroke of 99%. Several other clinical features can be seen in MELAS, including gastrointestinal dysmotility, neuropathy, ataxia, and psychiatric symptoms. Diabetes is also a common feature of this disease.
A: There is currently no specific treatment for MELAS, so the focus is on supportive therapy for the chronic symptoms and management of acute events. After the diagnosis is made, a comprehensive survey of organ function is required, followed by periodic monitoring, since complications can be subclinical and, if they are identified, can be treated proactively in a multidisciplinary fashion. Despite the lack of any convincing efficacy or safety data from clinical trials, cofactors and vitamin supplementation that are aimed at increasing ATP production and decreasing oxidative stress have been a mainstay of therapy for mitochondrial diseases. This treatment is known as the “mito cocktail.” Infusion of intravenous l-arginine (the precursor of nitric oxide) has recently been shown to prevent and improve acute stroke episodes, most likely by inducing vasodilation and improving tissue oxygenation. Also, long-term therapy with oral l-arginine is thought to decrease the frequency of strokelike episodes. Several clinical trials of therapies for the broad group of mitochondrial diseases are under way. The trials are still in early stages (phase 2) and investigate the use of several compounds with different mechanisms of action.