ISOLATED HORIZONTAL SUPRANUCLEAR GAZE PALSY AS A MARKER OF SEVERE SYSTEMIC INVOLVEMENT IN GAUCHERS-DISEASE

Type 3 neuronopathic Gaucher's disease (GD3) is phenotypically heterog eneous. In many GD3 patients, progressive myoclonus and dementia domin ate the illness, with death secondary to progressive CNS disease. We h ave designated this group as GD3a. We studied 14 children with Gaucher 's disease, isolated horizontal supranuclear gaze palsy, and aggressiv e systemic disease, and designated this group as GD3b. In comparison w ith 13 children with type 1 non-neuronopathic Gaucher's disease, the G D3b children presented earlier, and were shorter, underweight, and mor e prone to cardiopulmonary, hepatic, and skeletal complications. One-h alf of the children died in childhood or adolescence of systemic compl ications. Patients with at least one copy of the mutation that causes substitution of asparagine for serine at amino acid 370 of glucocerebr osidase 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 th erapy promise to improve the prognosis in GD3b.