title: Early-onset severe neurological involvement and D409H homozygosity in Gaucher disease: outcome of enzyme replacement therapy.
abstract: Gaucher disease, in most cases, is the result of mutations in the beta-glucocerebrosidase gene. More than 150 such mutations have been identified so far. Mutation D409H is the second most frequent in Greek patients, accounting for 15.5% of all identified mutated alleles. D409H homozygosity has, so far, been associated with a unique type III subtype of Gaucher disease that is characterized by the presence of devastating valvular heart disease, oculomotor apraxia, and, sometimes, features normally associated with mucopolysaccharidoses or oligosaccharidoses. Common manifestations of Gaucher disease tend to be less evident or even absent. We report the first Greek patient bearing the D409H/D409H genotype with onset of the disease in the first months of life and a phenotype dominated by severe neurological involvement. Enzyme replacement therapy, while improving the hematological parameters and organomegaly, failed to improve or even arrest the neurological condition.
authors.affiliation: Department of Enzymology and Cellular Function, Ag. Sophia Children's Hospital, 11527 Athens, Greece. inchildh@otenet.gr
authors.forename: H
authors.initials: H
authors.lastname: Michelakakis
authors.forename: A
authors.initials: A
authors.lastname: Skardoutsou
authors.forename: J
authors.initials: J
authors.lastname: Mathioudakis
authors.forename: M
authors.initials: M
authors.lastname: Moraitou
authors.forename: E
authors.initials: E
authors.lastname: Dimitriou
authors.forename: C
authors.initials: C
authors.lastname: Voudris
authors.forename: Th
authors.initials: T
authors.lastname: Karpathios
mesh_terms: D017668:Age of Onset; D057487:Enzyme Therapy; D004798:Enzymes / Q000008:administration & dosage; D005192:Family Health; D017809:Fatal Outcome; D005260:Female; D005776:Gaucher Disease / Q000150:complications / Q000235:genetics*; D005962:Glucosylceramidase / Q000008:administration & dosage / Q000235:genetics* / Q000627:therapeutic use; D006115:Greece; D006720:Homozygote; D006801:Humans; D007223:Infant; D009422:Nervous System Diseases / Q000201:enzymology*; D017354:Point Mutation
chemical_list: D004798:Enzymes; C070292:alglucerase; D005962:Glucosylceramidase