TY  - CHAP
M1  - Book, Section
TI  - Hereditary Renal Hypouricemia
A1  - Sperling, Oded
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  - Hereditary  renal  hypouricemia  (MIM  242050  and  307830)  is  an  inborn  error  of  membrane  transport,  presumably  in  urate  reabsorption  in  the  proximal  tubule.  It  is  inherited  in  an  autosomal  recessive  manner.  In  homozygotes,  it  manifests  as  hypouricemia  and  increased  renal  urate  clearance.  Heterozygosity  may  be  detected  by  moderately  decreased  serum  urate  levels  and  moderately  but  significantly  increased  renal  urate  clearance.Homozygosity  is  associated  with  moderate  or  excessive  uricosuria,  reflecting  the  diversion  of  intestinal  urate  elimination  to  urinary  urate  excretion  consequent  to  the  hypouricemia.  There  is  no  evidence  for  purine  overproduction.  Hypercalciuria,  probably  of  the  hyperabsorptive  type,  is  associated  with  renal  hypouricemia  in  about  20  percent  of  the  propositi.  The  mechanism  for  this  abnormality  is  not  yet  clarified.  The  hyperuricosuria  and/or  hypercalciuria  are  etiologic  factors  in  uric  acid  or  calcium  oxalate  urolithiasis,  occurring  in  about  25  percent  of  the  propositi.Transport  of  urate  through  the  intestinal  wall  and  through  the  erythrocyte  membrane  appears  to  be  normal.The  differential  diagnosis  of  hereditary  renal  hypouricemia  includes  familial  conditions,  in  which  the  defective  renal  urate  transport  is  one  component  in  a  generalized  transport  abnormality,  such  as  Hartnup  syndrome  or  the  group  of  diseases  with  Fanconi  renal  tubulopathy  (Wilson  disease,  cystinosis,  galactosemia,  and  hereditary  fructose  intolerance).The  model  of  the  renal  handling  of  urate  in  humans  includes  four  components:  free  glomerular  filtration,  net  early  proximal  tubular  reabsorption  (segment  S1),  net  tubular  secretion  (segment  S2),  and  net  postsecretory  tubular  reabsorption  (segment  S3).  It  is  assumed  that  reabsorption  and  secretion  of  urate  in  the  proximal  tubule  occur  simultaneously  and  that  the  manifestation  of  net  reabsorption  or  secretion  at  the  various  segments  reflects  different  intensities  of  the  two  processes.  The  residual  urinary  urate  in  the  S1  region  derives  originally  from  filtration,  whereas  that  in  the  S3  segment  arises  from  secretion  in  the  S2  segment.Several  types  of  renal  hypouricemia  may  be  distinguished,  according  to  the  nature  and  site  of  the  transport  defect.  The  classification  is  based  on  present  knowledge  concerning  the  renal  handling  of  urate  in  humans  and  on  the  mechanism  of  action  of  pyrazinamide  (assumed  to  inhibit  specifically  urate  secretion)  and  probenecid  (assumed  to  inhibit  specifically  urate  reabsorption  at  the  postsecretory  site).  In  hereditary  renal  hypouricemia,  the  most  common  type  appears  to  be  that  of  a  presecretory  reabsorption  defect.  Some  of  patients  may  have  a  total  transport  defect  (no  reabsorption,  no  secretion)  or  total  reabsorption  defect.  A  postsecretory  reabsorption  defect  has  not  been  documented  in  hereditary  renal  hypouricemia  but  was  found  to  characterize  acquired  renal  hypouricemia  and  familial  conditions  in  which  renal  hypouricemia  is  a  part  of  a  generalized  tubular  reabsorption  defect  (Fanconi  syndrome).  A  hypersecretion  defect  was  suggested  in  one  family  with  hereditary  renal  hypouricemia  and  in  three  patients  with  isolated  renal  hypouricemia  without  evidence  for  an  hereditary  basis.  
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/19
UR  - ommbid.mhmedical.com/content.aspx?aid=1181473796
ER  -