title: Early manifestations of type 1 Gaucher disease in presymptomatic children diagnosed after parental carrier screening.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.Genet Med advance online publication 13 October 2016.
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Amy C
authors.identifier: 0000-0002-0196-6136
authors.initials: AC
authors.lastname: Yang
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Louise
authors.identifier: 0000-0001-9692-5611
authors.initials: L
authors.lastname: Bier
authors.affiliation: Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Jessica R
authors.identifier: 0000-0001-7283-1661
authors.initials: JR
authors.lastname: Overbey
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Cohen-Pfeffer
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Khyati
authors.initials: K
authors.lastname: Desai
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Robert J
authors.identifier: 0000-0001-5501-2971
authors.initials: RJ
authors.lastname: Desnick
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Manisha
authors.initials: M
authors.lastname: Balwani
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005776:Gaucher Disease / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D006580:Genetic Carrier Screening; D005817:Genetic Counseling; D006596:Hexosaminidases / Q000378:metabolism; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D010290:Parents; D012720:Severity of Illness Index
chemical_list: D006596:Hexosaminidases; C086400:chitotriosidase