TY - JOUR
T1 - Early manifestations of type 1 Gaucher disease in presymptomatic children diagnosed after parental carrier screening
AU - Yang, Amy C.
AU - Bier, Louise
AU - Overbey, Jessica R.
AU - Cohen-Pfeffer, Jessica
AU - Desai, Khyati
AU - Desnick, Robert J.
AU - Balwani, Manisha
N1 - Publisher Copyright:
© 2016 American College of Medical Genetics and Genomics.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Purpose:The overall published experience with pediatric type 1 Gaucher disease (GD1) has been based on ascertainment through clinical presentation of the disease. We describe the longitudinal follow-up in a presymptomatic pediatric cohort.Methods:The cohort includes children diagnosed with GD1, either prenatally or postnatally by molecular genetic testing, and followed for clinical care at our center from 1998 to 2016. All patients' parents were GBA mutation carriers identified through carrier screening programs. Longitudinal clinical, laboratory, and imaging data were obtained through chart review.Results:Thirty-eight patients aged 1-18 years (mean at last visit 6.9 ± 4.1 years) were followed, including 32 p.N409S homozygotes and 6 p.N409S/p.R535H compound heterozygotes. At the last evaluation, a minority had hematological (5%), bone (15%), or linear growth (19%) issues. Only 12% had splenomegaly and 74% had moderate hepatomegaly. Chitotriosidase activity varied widely (6-5,640 nmol/hour/ml) and generally increased with age. Pediatric Gaucher severity scores (GSS) remained stable and within the mild-disease range for most (95%). Treatment for progressive disease during this period was recommended for four children.Conclusion:Most children with the p.N409S/p.N409S and p.N409S/p.R535H GD1 genotypes have minimal disease manifestations and progression during childhood and can be monitored using limited assessments. Those with other mutations may require additional monitoring. These data are valuable for newborn screening and counseling.
AB - Purpose:The overall published experience with pediatric type 1 Gaucher disease (GD1) has been based on ascertainment through clinical presentation of the disease. We describe the longitudinal follow-up in a presymptomatic pediatric cohort.Methods:The cohort includes children diagnosed with GD1, either prenatally or postnatally by molecular genetic testing, and followed for clinical care at our center from 1998 to 2016. All patients' parents were GBA mutation carriers identified through carrier screening programs. Longitudinal clinical, laboratory, and imaging data were obtained through chart review.Results:Thirty-eight patients aged 1-18 years (mean at last visit 6.9 ± 4.1 years) were followed, including 32 p.N409S homozygotes and 6 p.N409S/p.R535H compound heterozygotes. At the last evaluation, a minority had hematological (5%), bone (15%), or linear growth (19%) issues. Only 12% had splenomegaly and 74% had moderate hepatomegaly. Chitotriosidase activity varied widely (6-5,640 nmol/hour/ml) and generally increased with age. Pediatric Gaucher severity scores (GSS) remained stable and within the mild-disease range for most (95%). Treatment for progressive disease during this period was recommended for four children.Conclusion:Most children with the p.N409S/p.N409S and p.N409S/p.R535H GD1 genotypes have minimal disease manifestations and progression during childhood and can be monitored using limited assessments. Those with other mutations may require additional monitoring. These data are valuable for newborn screening and counseling.
UR - http://www.scopus.com/inward/record.url?scp=85020233760&partnerID=8YFLogxK
U2 - 10.1038/gim.2016.159
DO - 10.1038/gim.2016.159
M3 - Article
C2 - 27735925
AN - SCOPUS:85020233760
SN - 1098-3600
VL - 19
SP - 652
EP - 658
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 6
ER -