TY  - CHAP
M1  - Book, Section
TI  - Disorders of Histidine Metabolism
A1  - Levy, Harvey L.
A1  - Taylor, Robin G.
A1  - McInnes, Roderick R.
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  - There  are  two  known  disorders  of  histidine  metabolism:  histidinemia  and  urocanic  aciduria.  Histidinemia  is  one  of  the  most  frequent  and  well  known  of  the  inborn  errors  of  metabolism.  A  test  for  it  has  been  included  in  newborn  screening  programs,  and  its  incidence  was  about  1:12,000  in  over  20  million  screened  infants.  The  frequency  is  particularly  high  in  Japan  (1:9600).  It  is  an  autosomal  recessive  trait  and  is  due  to  a  defect  in  histidase,  which  catalyzes  the  conversion  of  histidine  to  urocanic  acid.  This  enzyme  defect  is  most  readily  identified  in  the  stratum  corneum  of  skin.  The  biochemical  consequences  of  the  metabolic  block  include  increased  concentrations  of  histidine  in  blood,  urine,  and  cerebrospinal  fluid  (CSF);  decreased  concentration  of  urocanic  acid  in  blood  and  skin;  and  increased  concentrations  of  histidine  metabolites  in  urine.  Histidinemia  seems  to  be  benign  in  most  affected  individuals,  although,  under  certain  unusual  circumstances,  the  disorder  may  be  harmful  and  produce  the  central  nervous  system  disease  noted  in  a  few  histidinemic  patients.  Dietary  treatment  lowers  the  blood  histidine  level  but  seems  not  to  be  indicated,  at  least  for  most  patients,  given  the  apparent  lack  of  consequences  of  the  disorder.  Urocanic  aciduria  is  an  apparently  autosomal  recessive  disorder.  It  is  probably  benign.  An  increased  concentration  of  urocanic  acid  in  urine  is  the  only  known  metabolic  finding.The  prominence  of  histidinemia  has  stimulated  the  study  of  histidase,  an  enzyme  expressed  primarily  in  liver  and  skin  and  regulated  in  a  complex  developmental,  hormonal,  and  tissue-specific  manner.  At  the  molecular  level,  the  enzyme  is  unusual  in  having  a  rare  modified  amino  acid,  dehydroalanine,  in  its  active  site.  Full-length  cDNAs  of  human,  rat,  and  mouse  liver  histidase  have  been  isolated.  The  human  gene  has  also  been  cloned  and  characterized:  It  is  a  single-copy  gene  spanning  approximately  25  kb  and  consisting  of  21  exons.  Several  liver-  and  epidermis-specific  transcription  factor-binding  sites  have  been  identified  in  the  5′  flanking  region.  A  polymorphism  has  been  identified  in  exon  16.  The  gene  has  not  yet  been  studied  for  mutations  in  histidinemic  patients.The  deficiency  of  urocanic  acid  in  histidinemia  could  have  implications  for  either  or  both  of  two  proposed  functions  of  urocanic  acid—as  a  natural  sunscreen  against  ultraviolet  (UV)  light  and  as  a  mediator  of  ultraviolet  light-induced  systemic  immunosuppression.  As  yet,  there  has  been  no  evidence  for  impairment  of  either  of  these  proposed  functions  in  histidinemia,  but  further  study  of  this  question  might  be  warranted.Atypical  histidinemia  is  a  biochemically  milder  form  of  the  disorder  and  may  account  for  a  substantial  minority  of  persons  with  histidinemia.  The  reported  individuals  have  been  clinically  normal.  They  have  higher  residual  skin  histidase  activities  and  lower  elevations  of  histidine  and  histidine  metabolites  than  individuals  with  the  classic  disorder.  Histidinemia  may  be  a  biochemically  heterogeneous  disorder,  perhaps  due  to  several  allelic  mutations.Maternal  histidinemia  is  probably  benign.  The  61  offspring  from  untreated  pregnancies  of  23  histidinemic  mothers  whose  cases  have  been  followed  have  generally  been  normal.An  animal  model  with  the  biochemical  features  of  human  histidinemia  has  been  identified.  The  histidinemic  mouse  has  a  missense  mutation  in  the  coding  region  ...
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/18
UR  - ommbid.mhmedical.com/content.aspx?aid=1181434502
ER  -