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Título

MELAS SYNDROME – MOTHER AND DAUGHTER WITH RARE MUTATION (3291) IN MITOCHONDRIAL DNA

RESUMO

CASE PRESENTATION:
BVSM, 11 years old, in early childhood difficulty in gaining weight and median school performance due to inattention. At 9 years of age, he started to have epilepsy associated with severe metabolic acidosis. After 1 year, the patient evolved with visual scotomas, headache, vomiting, daily seizures, right hemiparesis, fatigue and palpitations. At the time, she underwent tests that showed an increase in lactate, magnetic resonance imaging (MRI) of the skull with ischemic stroke (IS) and echocardiogram with the presence of dilated cardiomyopathy.
Genetic tests were requested to investigate the underlying pathology, and a mutation was found in the mitochondrial gene MT-TL1, variant c.3291T>C in heteroplasmy (71%), closing the diagnosis for MELAS. The patient died in a few months from congestive heart failure.
Due to the mitrochondropathy, a genetic investigation of the mother was guided, and the same mutation was found (heteroplasmy in 32%). She was asymptomatic and recently had an unprecedented seizure.

DISCUSSION:
In MELAS syndrome (mitochondrial encephalopathy, lactic acidosis and stroke) there is a genetic mutation that compromises the mitochondrial DNA, being exclusively maternally transmitted. Mitochondria generate ATP, and their dysfunctions lead to energy insufficiency for various organs. The clinical diagnosis is based on the presence of IS (<40 years), encephalopathy (convulsions/dementia), mitochondrial myopathy (lactic acidosis and/or irregular red fibers), criteria found in the patient in the case in question. The disease can lead to other symptoms such as headache, vomiting, dementia, deafness, diabetes, short stature and cardiomyopathy.
About 80% of cases result from leucine tRNA mutation, with m.3243A>G being the most common. The c.3291T>C variant, present in the patient, is found in <1% of cases. MRI lesions are not classic, restricted to the cortex and subcortical white matter. In spectroscopy there is a reduction of n-acetylaspartate and accumulation of lactate. Treatment is symptomatic and with a multidisciplinary team. Antioxides and cofactors can be administered with the aim of improving quality of life and reducing the risk of complications.

FINAL COMMENTS:
MELAS presents different phenotypes in the same mutation, making it a diagnostic challenge. Still intractable and with devastating consequences as in the case described, it is expected that in future research new medications can bring better quality of life to patients.

Palavras Chave

MELAS syndrome; mitochondriopathy

Área

Neurogenética