Mystery Case: Lafora periodic acid-Schiff inclusion bodies.

A 16-year-old boy presented with a 5-year history of progressive cognitive decline and behavioral change followed by generalized tonic-clonic and myoclonic seizures refractory to many anticonvulsants (valproic acid, phenobarbital, clonazepam, and topiramate) and cerebellar ataxia a year later. The son of consanguineous parents, he had a family history of 2 cousins who both had epilepsy and died at the ages of 15 and 25 years. Laboratory screening tests, including lactic acid, fundus examination, brain neuroimaging, and CSF, were normal. Skin biopsy (figure) revealed periodic acid–Schiff-positive intracellular polyglucosan inclusion bodies in myoepithelial and sweat gland duct cells. These findings are typical of Lafora disease, a fatal autosomal recessive disorder caused by mutations in one of 2 known genes, both located at chromosome 6: EPM2A, which encodes the protein laforin, and EPM2B, which encodes the protein malin. Differential diagnosis must be made with other causes of progressive myoclonic epilepsies, most commonly Unverricht-Lundborg disease (Baltic myoclonus), myoclonus epilepsy and ragged-red fibers syndrome, neuronal ceroid lipofuscinosis, and type 1 sialidosis. There is no treatment, and therapy is mainly supportive and symptomatic. AUTHOR CONTRIBUITONS All authors contributed equally to the study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, and administrative, technical, and material support.