Differential diagnosis
The presentation of some cases is similar to that of Kearns–Sayre syndrome.Myoclonus epilepsy associated with ragged red fibers (MERRF) may be confused with MELAS as they both involve seizures, mental deterioration, and myopathy with ragged red fibers on biopsy. MERRF patients may also have hearing loss, visual disturbance secondary to optic atrophy, and short stature. The characteristic myoclonic seizure in MERRF may help to narrow diagnosis, but genetic testing should be considered to distinguish the two conditions.Leigh syndrome may also present with progressive neurological deterioration, seizures, and vomiting mainly in young children. Genetics
MELAS is mostly caused by mutations in the genes in mitochondrial DNA, but it can also be caused by mutations in the nuclear DNA. NADH dehydrogenase
Some of the genes (MT-ND1, MT-ND5) affected in MELAS encode proteins that are part of NADH dehydrogenase (also called complex I) in mitochondria, that helps convert oxygen and simple sugars to energy. Transfer RNAs
Other genes (MT-TH, MT-TL1, and MT-TV) encode mitochondrial specific transfer RNAs (tRNAs).Mutations in MT-TL1 cause more than 80 percent of all cases of MELAS. They impair the ability of mitochondria to make proteins, use oxygen, and produce energy. Researchers have not determined how changes in mitochondrial DNA lead to the specific signs and symptoms of MELAS. They continue to investigate the effects of mitochondrial gene mutations in different tissues, particularly in the brain. Inheritance
This condition is inherited in a mitochondrial pattern, which is also known as maternal inheritance and heteroplasmy. This pattern of inheritance applies to genes contained in mitochondrial DNA.
Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, only females pass mitochondrial conditions to their children. Mitochondrial disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass mitochondrial traits to their children. In most cases, people with MELAS inherit an altered mitochondrial gene from their mother. Less commonly, the disorder results from a new mutation in a mitochondrial gene and occurs in people with no family history of MELAS. Diagnosis
MRI: Multifocal infarct-like cortical areas in different stages of ischemic evolution, areas that do not conform to any known vascular territory. Initial lesions often occur in the occipital or parietal lobes with eventual involvement of the cerebellum, cerebral cortex, basal ganglia, and thalamus.Lactate levels are often elevated in serum and cerebrospinal fluid. MR spectroscopy may show an elevated lactate peak in affected and even unaffected brain areas. Muscle biopsy shows ragged red fibers. However, genetic evaluation should be done first, which eliminates the need for muscle biopsy in most cases. Diagnosis may be molecular or clinical:
Stroke-like episodes before or after 40 years old
Encephalopathy with seizures or dementia
Blood lactic acidosis* or ragged red fibers on muscle biopsyDue to mitochondrial heteroplasmy, urine and blood testing is preferable to blood alone. PCR and ARMS-PCR are commonly used, reliable, rapid, and cost-effective techniques for the diagnosis of MELAS.Hearing loss and mitochondrial diabetes are common features. Eyes may have a distinctive speckled pigment in the retina, referred to as a maculopathy. Family members may present differently.