RT Book, Section
A1 Grabowski, Gregory A.
A1 Kolodny, Edwin H.
A1 Weinreb, Neal J.
A1 Rosenbloom, Barry E.
A1 Prakash-Cheng, Ainu
A1 Kaplan, Paige
A1 Charrow, Joel
A1 Pastores, Gregory M.
A1 Mistry, Pramod K.
A2 Valle, David L.
A2 Antonarakis, Stylianos
A2 Ballabio, Andrea
A2 Beaudet, Arthur L.
A2 Mitchell, Grant A.
SR Print(0)
ID 1181465491
T1 Gaucher Disease: Phenotypic and Genetic Variation
T2 The Online Metabolic and Molecular Bases of Inherited Disease
YR 2019
FD 2019
PB McGraw-Hill Education
PP New York, NY
SN 9780071459969
LK ommbid.mhmedical.com/content.aspx?aid=1181465491
RD 2024/04/18
AB The  marked  phenotypic  variation  within  and  among  the  Gaucher  disease  clinical  types  has  been  known  for  several  decades,  but  the  characterization  of  this  variation  has  generally  been  limited  to  relatively  small  patient  populations  (Sibille  et  al,148;  Zimran  et  al,194;  Zimran  et  al,191;  Zimran  et  al,192).  In  addition,  these  characterizations  are  skewed  because  of  the  ascertainment  bias  in  European-derived  and,  specifically,  Ashkenazi  Jewish  populations.  With  broader  knowledge  about  the  major  phenotypes,  known  as  types  1,  2,  and  3,  the  understanding  of  a  spectrum  or  continuum  has  evolved  with  regard  to  clinical/pathologic  involvement,  particularly  for  the  neuronopathic  variants  (Table  184-1;  Fig.  184-1A).  Excluding  CNS  involvement,  the  continuum  extends  to  the  variation  in  the  visceral  disease  of  overlapping  involvement  among  and  between  type  1,  2,  and  3  diseases  (Fig.  184-1B).  The  advent  of  specific  therapies  for,  the  need  for  early  prognostication  in,  and  the  search  for  modifying  agents  of  Gaucher  disease  make  complex  phenotyping  not  merely  an  academic  nosologic  exercise,  but  of  major  practical  and  basic  import.  Thus,  such  distinctions  impact  whole-life  medical  care  delivery,  reproductive  decisions,  and  therapeutic  choices  for  affected  families.  Importantly,  approaches  to  presymptomatic  or  prospective  intervention  therapies  and/or  use  of  therapies  with  significant  risk  require  accurate  risk-benefit  analyses  based  on  the  prognosis  for  individual  patients.  Detailed  phenotyping  and  correlations  to  genotype  could  provide  insight  into  individual  susceptibility  to  varying  disease  severity.  This  need  represents  a  prime  motivation  to  correlate  phenotypes  and  genotypes  in  Gaucher  disease  as  well  as  other  inherited  disorders.