Clinical and genetic study of Japanese patients with type 3 Gaucher disease.
Information on the phenotypic variations seen in patients with type 3 (chronic neuronopathic) Gaucher disease (GD) is still limited compared with type 1 GD. We retrospectively investigated the clinical features of 42 Japanese patients with type 3 GD. The 42 patients classified as type 3 fell into two groups: those diagnosed as having type 3 GD at diagnosis (group A; n = 24) and those thought to have type 1 at diagnosis but who later developed neurological symptoms (group B; n = 18). The genotype of group A patients varied widely; however, L444P/L444P and L444P/F213I genotypes accounted for 83% in group B. All the patients who did not receive enzyme replacement with alglucerase or imiglucerase (4 in group A, 2 in group B) died. Nineteen patients received enzyme replacement in group A; however, 7 of these died despite the therapy. On the other hand, 14 patients received enzyme replacement alone in group B and 13 of them survived. Among the ERT-treated patients who survived, only one of 12 in group A and 12 out of 13 in group B can walk unaided. In conclusion, some Japanese GD patients who are thought to have type 1 at diagnosis develop neurological symptoms during their clinical course, and careful observation is essential for patients with characteristic genotypes. Moreover, enzyme replacement alone might not have a sufficient effect on the early onset neurological symptoms in type 3 patients. A different treatment strategy is needed to improve the prognosis of these patients.
Tajima
Asako
A
Department of Pediatrics, Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan. atajima@jikei.ac.jp
Yokoi
Takayuki
T
Ariga
Masamichi
M
Ito
Takeru
T
Kaneshiro
Eiko
E
Eto
Yoshikatsu
Y
Ida
Hiroyuki
H
D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D005776:Gaucher Disease / Q000188:drug therapy / Q000235:genetics*; D005838:Genotype; D005962:Glucosylceramidase / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012189:Retrospective Studies; D016896:Treatment Outcome
C070292:alglucerase; D005962:Glucosylceramidase; C090568:imiglucerase