MERRF

MERRF, or myoclonic epilepsy with ragged-red fibers, is a mitochondrial disorder characterized by myoclonic jerks and epilepsy, often accompanied by progressive myopathy and ataxia. The hallmark histological finding is ragged-red fibers seen in muscle biopsy with special stains, reflecting abnormal mitochondria accumulated under the muscle cell membrane. Onset typically occurs in childhood or adolescence but can appear later, and symptoms progress at variable rates.

Genetically, MERRF is caused by mutations in mitochondrial DNA, most commonly in the tRNA-Lys gene (MT-TK). The A8344G mutation is the most frequent, but other MT-TK mutations and rare mtDNA changes can cause a MERRF-like syndrome. Because mitochondrial DNA is inherited maternally, affected individuals pass the mutation to all offspring, though disease expression depends on heteroplasmy—the mixture of normal and mutated mitochondria—and tissue distribution, leading to variable severity even within families.

Clinical features include myoclonic epilepsy, generalized tonic-clonic seizures, progressive muscle weakness, exercise intolerance, ataxia, and dysarthria. Additional manifestations can involve hearing loss, ophthalmoplegia, and mitochondrial lactic acidosis in some cases. Diagnosis combines clinical assessment, elevated lactate levels, muscle biopsy showing ragged-red fibers, and confirmatory genetic testing for MT-TK mutations.

Management is supportive and multidisciplinary. Antiepileptic treatment aims to control seizures but valproate is generally avoided in mitochondrial disorders due to safety concerns; alternatives such as levetiracetam, lamotrigine, or clonazepam may be used. Supplements like coenzyme Q10 or L-carnitine are used variably. Physical therapy, occupational therapy, and regular monitoring for multisystem involvement are important. The prognosis is variable and largely depends on the mutation load and extent of organ involvement.