Tamar H. Taddei and Katherine A. Kacena contributed equally to this work.
The underrecognized progressive nature of N370S Gaucher disease and assessment of cancer risk in 403 patients†
Article first published online: 12 JAN 2009
Copyright © 2009 Wiley-Liss, Inc.
American Journal of Hematology
Volume 84, Issue 4, pages 208–214, April 2009
How to Cite
Taddei, T. H., Kacena, K. A., Yang, M., Yang, R., Malhotra, A., Boxer, M., Aleck, K. A., Rennert, G., Pastores, G. M. and Mistry, P. K. (2009), The underrecognized progressive nature of N370S Gaucher disease and assessment of cancer risk in 403 patients. Am. J. Hematol., 84: 208–214. doi: 10.1002/ajh.21362
Conflict of interest: PKM receives a research grant from Genzyme Corporation for participation in the International Gaucher Registry.
- Issue published online: 25 MAR 2009
- Article first published online: 12 JAN 2009
- Accepted manuscript online: 12 JAN 2009 12:00AM EST
- Manuscript Accepted: 6 JAN 2009
- Manuscript Received: 2 JAN 2009
- NIH NIDDK. Grant Numbers: T32DK007356, P30DK34989
- NIDDK. Grant Number: K24DK066306
- AASLD/ALF Sheila Sherlock Award
- NIH CTSA/Yale Center for Clinical Investigation Scholar Award
- Howard Hughes Patient-Oriented Research Pilot Project Grant
- National Gaucher Foundation
Mutations in GBA1 gene that encodes lysosomal glucocerebrosidase result in Type 1 Gaucher Disease (GD), the commonest lysosomal storage disorder; the most prevalent disease mutation is N370S. We investigated the heterogeneity and natural course of N370S GD in 403 patients. Demographic, clinical, and genetic characteristics of GD at presentation were examined in a cross-sectional study. In addition, the relative risk (RR) of cancer in patients compared with age-, sex-, and ethnic-group adjusted national rates of cancer was determined. Of the 403 patients, 54% of patients were homozygous (N370S/N370S) and 46% were compound heterozygous for the N370S mutation (N370S/other). The majority of N370S/N370S patients displayed a phenotype characterized by late onset, predominantly skeletal disease, whereas the majority of N370S/other patients displayed early onset, predominantly visceral/hematologic disease, P < 0.0001. There was a striking increase in lifetime risk of multiple myeloma in the entire cohort (RR 25, 95% CI 9.17–54.40), mostly confined to N370S homozygous patients. The risk of other hematologic malignancies (RR 3.45, 95% CI 1.49–6.79), and overall cancer risk (RR 1.80, 95% CI 1.32–2.40) was increased. Homozygous N370S GD leads to adult-onset progressive skeletal disease with relative sparing of the viscera, a strikingly high risk of multiple myeloma, and an increased risk of other cancers. High incidence of gammopathy suggests an important role of the adaptive immune system in the development of GD. Adult patients with GD should be monitored for skeletal disease and cancers including multiple myeloma. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc.