title: Hepatic disease as the first manifestation of progressive myoclonus epilepsy of Lafora.
abstract: BACKGROUND
  Lafora disease (LD; progressive myoclonus epilepsy type 2; EPM2) is an autosomal recessive disorder caused by mutations in the EPM2A and EPM2B genes. LD is characterized by the presence of strongly PAS-positive intracellular inclusions (Lafora bodies) in several tissues. Glycogen storage disease type IV (GSD-IV; Andersen disease) is an autosomal recessive disorder characterized by cirrhosis leading to severe liver failure. GSD-IV has been associated with mutations in the glycogen branching enzyme gene (GBE). Histopathologic changes of the liver in both diseases show an identical appearance, although cirrhosis has never been described in patients with LD. We report a LD family in which the proband presented severe liver failure at onset of the disease.
  
  
  METHODS
  Clinical histories, physical and neurologic examination, laboratory tests, EEGs, MRI of the brain, and liver or axillary skin biopsies were performed in the two affected siblings. The diagnosis was confirmed by molecular genetic analysis of the EPM2A, EPM2B, and GBE genes and loci.
  
  
  RESULTS
  During the first decade of life, abnormalities in liver function tests were detected in the two affected siblings. The proband's liver dysfunction was severe enough to require liver transplantation. Subsequently, both sibs developed LD. Mutation analysis of EPM2A revealed a homozygous Arg241stop mutation in both patients.
  
  
  CONCLUSIONS
  This is the first description of severe hepatic dysfunction as the initial clinical manifestation of LD. The phenotypic differences between the two affected siblings suggest that modifier genes must condition clinical expression of the disease outside the CNS.
authors: Laboratorio y Servicio de Neurología, Fundación Jiménez Díaz, Madrid, Spain.
authors: P
authors: P
authors: Gómez-Garre
authors: E
authors: E
authors: Gutiérrez-Delicado
authors: C
authors: C
authors: Gómez-Abad
authors: J
authors: J
authors: Morales-Corraliza
authors: V E
authors: VE
authors: Villanueva
authors: S
authors: S
authors: Rodríguez de Córdoba
authors: J
authors: J
authors: Larrauri
authors: M
authors: M
authors: Gutiérrez
authors: J
authors: J
authors: Berciano
authors: J M
authors: JM
authors: Serratosa
mesh_terms: D015061:1,4-alpha-Glucan Branching Enzyme / Q000235:genetics; D001706:Biopsy; D001921:Brain / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D018389:Codon, Nonsense; D003937:Diagnosis, Differential; D018450:Disease Progression; D004392:Dwarfism / Q000209:etiology; D004569:Electroencephalography; D005091:Exons / Q000235:genetics; D006011:Glycogen Storage Disease Type IV / Q000175:diagnosis; D006801:Humans; D007223:Infant; D020192:Lafora Disease / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology; D017093:Liver Failure / Q000209:etiology* / Q000601:surgery; D016031:Liver Transplantation; D008279:Magnetic Resonance Imaging; D008297:Male; D018895:Microsatellite Repeats; D020125:Mutation, Missense; D010375:Pedigree; D010503:Periodic Acid-Schiff Reaction; D010641:Phenotype; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D012867:Skin / Q000473:pathology; D013030:Spain; D044767:Ubiquitin-Protein Ligases
chemical_list: D002352:Carrier Proteins; D018389:Codon, Nonsense; C478960:NHLRC1 protein, human; D044767:Ubiquitin-Protein Ligases; D015061:1,4-alpha-Glucan Branching Enzyme; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C114990:EPM2A protein, human