title: Isolated horizontal supranuclear gaze palsy as a marker of severe systemic involvement in Gaucher's disease.
abstract: Type 3 neuronopathic Gaucher's disease (GD3) is phenotypically heterogeneous. In many GD3 patients, progressive myoclonus and dementia dominate the illness, with death secondary to progressive CNS disease. We have designated this group as GD3a. We studied 14 children with Gaucher's disease, isolated horizontal supranuclear gaze palsy, and aggressive systemic disease, and designated this group as GD3b. In comparison with 13 children with type 1 non-neuronopathic Gaucher's disease, the GD3b children presented earlier, and were shorter, underweight, and more prone to cardiopulmonary, hepatic, and skeletal complications. One-half of the children died in childhood or adolescence of systemic complications. Patients with at least one copy of the mutation that causes substitution of asparagine for serine at amino acid 370 of glucocerebrosidase did not develop neurologic signs. Patients homoallelic for the mutation causing substitution of leucine for proline at position 444 had severe systemic disease; neurologic signs were frequently, but not invariably, present. Early diagnosis and timely enzyme replacement therapy promise to improve the prognosis in GD3b.
authors.affiliation: Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892.
authors.forename: M C
authors.initials: MC
authors.lastname: Patterson
authors.forename: M
authors.initials: M
authors.lastname: Horowitz
authors.forename: R B
authors.initials: RB
authors.lastname: Abel
authors.forename: J N
authors.initials: JN
authors.lastname: Currie
authors.forename: K T
authors.initials: KT
authors.lastname: Yu
authors.forename: C
authors.initials: C
authors.lastname: Kaneski
authors.forename: J J
authors.initials: JJ
authors.lastname: Higgins
authors.forename: R R
authors.initials: RR
authors.lastname: O'Neill
authors.forename: P
authors.initials: P
authors.lastname: Fedio
authors.forename: A
authors.initials: A
authors.lastname: Pikus
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000097:blood; D005500:Follow-Up Studies; D005776:Gaucher Disease / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology*; D005838:Genotype; D006801:Humans; D007223:Infant; D013494:Supranuclear Palsy, Progressive / Q000209:etiology* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D004247:DNA