RT Book, Section
A1 Hayden, Michael R.
A1 Kremer, Berry
A2 Valle, David L.
A2 Antonarakis, Stylianos
A2 Ballabio, Andrea
A2 Beaudet, Arthur L.
A2 Mitchell, Grant A.
SR Print(0)
ID 1181478521
T1 Huntington Disease
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=1181478521
RD 2024/04/20
AB Huntington  disease  (MIM  143100)  is  a  slowly  progressive  autosomal  dominant  neurodegenerative  disease.  Onset  is  usually  in  adult  life,  with  a  mean  of  around  40  years.  However,  onset  before  age  20  or  after  age  60  is  well  described.  The  disease  progresses  inexorably,  with  death  occurring  approximately  18  years  from  the  time  of  onset.  Prevalence  is  between  3  and  7  per  100,000  in  populations  of  western  European  descent,  but  Huntington  disease  (HD)  has  been  described  in  populations  of  many  different  ancestries.The  neuropathologic  hallmark  of  the  disease  is  neuronal  loss  and  gliosis  in  the  caudate  nucleus  and  the  putamen  (the  striatum),  with  resulting  atrophy.  Medium-sized  striatal  neurons  that  contain  gamma-aminobutyric  acid  and  enkephalin  or  gamma-aminobutyric  acid  and  substance  P  as  their  neurotransmitters  are  selectively  depleted.  Other,  neurochemically  distinct  striatal  neuronal  populations  are  spared,  such  as  large  aspiny  acetylcholinesterase-containing  neurons  or  NADPH-diaphorase  neurons  with  somatostatin  and  neuropeptide  Y.  Apart  from  the  striatum,  the  whole  brain  undergoes  generalized  atrophy.  No  specific  pathologic  changes  have  been  found  outside  the  central  nervous  system.Clinical  manifestations  consist  of  gradually  evolving  involuntary  movements,  progressive  dementia,  and  psychiatric  disturbances,  especially  mood  disorder  and  personality  changes.  Chorea  is  the  most  prominent  abnormality,  but  parkinsonism,  dystonia,  and  involuntary  motor  impairment  all  may  be  present.  Minor  motor  abnormalities,  including  clumsiness,  hyperreflexia,  and  eye  movement  disturbances,  often  appear  as  early  manifestations  of  HD.  Patients  with  onset  before  age  20  frequently  have  prominent  bradykinesia,  rigidity,  epilepsy,  severe  dementia,  and  a  shorter  duration  of  illness.  In  contrast,  cognitive  decline  is  often  less  severe  in  patients  with  onset  aftetr  age  60.In  1993,  a  novel  gene  containing  a  CAG  trinucleotide  repeat  that  is  expanded  on  HD  chromosomes  was  identified.  This  highly  polymorphic  CAG  repeat  located  in  the  5′  end  of  the  gene  has  been  shown  to  range  between  10  and  29  copies  on  normal  chromosomes,  whereas  it  is  expanded  to  a  range  of  36  to  121  on  HD  chromosomes.  The  vast  majority  of  patients  with  the  clinical  diagnosis  of  HD  have  expansion  of  the  CAG  repeat.  Age  of  onset  shows  a  highly  significant  association  with  the  length  of  the  CAG  repeat.The  biochemical  defect  underlying  HD  is  unknown.  Recent  data  suggest  that  cells  die  via  apoptotic  pathways.  Cleavage  of  huntingtin,  the  polypeptide  product  of  the  HD  gene,  into  a  smaller  fragment  containing  the  expanded  polyglutamine  tract  appears  to  be  an  important  step  in  pathogenesis  of  the  illness.  There  is  no  known  treatment  to  retard  disease  progression.  Neuroleptic  medication  is  able  to  alleviate  choreic  movements  to  some  extent,  but  side  effects  may  be  severe.  Antidepressant  therapy  may  be  helpful  in  the  early  stages  to  alleviate  the  mood  disorder.