TY  - CHAP
M1  - Book, Section
TI  - Lesch-Nyhan Disease and Its Variants
A1  - Jinnah, H. A.
A1  - Friedmann, Theodore
A2  - Valle, David L.
A2  - Antonarakis, Stylianos
A2  - Ballabio, Andrea
A2  - Beaudet, Arthur L.
A2  - Mitchell, Grant A.
PY  - 2019
T2  - The Online Metabolic and Molecular Bases of Inherited Disease
AB  - Inherited  deficiency  of  the  purine  salvage  enzyme  hypoxanthine-guanine  phosphoribosyltransferase  (HPRT)  causes  three  overlapping  clinical  syndromes,  depending  on  the  amount  of  residual  enzyme  activity.  Patients  with  at  least  8  percent  of  residual  enzyme  activity  demonstrate  marked  overproduction  of  uric  acid,  with  associated  hyperuricemia,  nephrolithiasis,  and  gout.  Patients  with  1.5  to  8  percent  of  residual  activity  demonstrate  uric  acid  overproduction  with  neurologic  disability  that  varies  from  minor  clumsiness  to  debilitating  extrapyramidal  and  pyramidal  motor  dysfunction.  Patients  with  less  than  1.5  percent  of  residual  activity  demonstrate  overproduction  of  uric  acid,  debilitating  neurologic  disability,  varying  degrees  of  cognitive  disability,  and  behavioral  abnormalities  that  include  impulsive  and  self-injurious  behaviors.  This  latter  and  most  severe  form  of  the  disease  is  known  as  Lesch-Nyhan  disease  (LND).HPRT  deficiency  is  inherited  as  an  X-linked  recessive  condition,  and  the  HPRT  gene  has  been  mapped  to  Xq26-q27.  The  entire  HPRT  gene  has  been  cloned  and  sequenced  and  more  than  200  mutations  responsible  for  disease  have  been  characterized.  These  advances  at  the  molecular  genetic  level  have  allowed  for  the  development  of  rapid  and  convenient  methods  for  diagnosis,  carrier  identification,  and  prenatal  testing.The  metabolic  basis  for  the  overproduction  of  uric  acid  in  HPRT  deficiency  has  been  determined  to  result  from  changes  in  the  regulation  of  purine  synthesis  and  degradation.  The  overproduction  of  uric  acid  can  be  blocked  by  the  administration  of  allopurinol,  providing  an  effective  means  to  reduce  the  risk  of  nephrolithiasis  and  gout  in  affected  patients.  Unfortunately,  allopurinol  has  no  efficacy  against  the  neurobehavioral  features.The  pathogenesis  of  the  neurologic  and  behavioral  features  remains  incompletely  understood,  although  growing  evidence  suggests  that  these  features  result  from  dysfunction  of  the  dopamine  transmitter  systems  of  the  basal  ganglia.  Treatments  for  the  neurobehavioral  features  are  limited  to  protective  physical  devices  and  behavior  therapy.Current  research  efforts  are  focused  on  prevention,  elucidating  the  basis  for  the  central  nervous  system  dysfunction,  and  developing  more  effective  treatment  strategies  for  the  neurobehavioral  features.  
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/24
UR  - ommbid.mhmedical.com/content.aspx?aid=1181440736
ER  -