TY  - CHAP
M1  - Book, Section
TI  - The Mucopolysaccharidoses
A1  - Neufeld, Elizabeth F.
A1  - Muenzer, Joseph
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  - The  mucopolysaccharidoses  (MPS)  are  a  group  of  lysosomal  storage  disorders  caused  by  deficiency  of  enzymes  catalyzing  the  degradation  of  glycosaminoglycans  (mucopolysaccharides).  Depending  on  the  enzyme  deficiency,  the  catabolism  of  dermatan  sulfate,  heparan  sulfate,  keratan  sulfate,  chondroitin  sulfate,  or  hyaluronan  may  be  blocked,  singly  or  in  combination.  Lysosomal  accumulation  of  glycosaminoglycan  molecules  results  in  cell,  tissue,  and  organ  dysfunction.  Glycosaminoglycan  fragments  generated  by  alternative  pathways  are  excreted  in  urine.  There  are  11  known  enzyme  deficiencies  that  give  rise  to  7  distinct  MPS.  Table  172-1  presents  the  affected  enzymes  and  glycosaminoglycans,  and  the  corresponding  syndromes  and  subtypes.The  stepwise  degradation  of  glycosaminoglycans  requires  four  exoglycosidases,  five  sulfatases,  and  one  nonhydrolytic  transferase.  Endoglycosidases  also  participate  in  the  degradation.  The  genes  and  cDNAs  encoding  most  of  these  enzymes  have  been  cloned,  leading  to  elucidation  of  their  primary  structure,  to  production  of  recombinant  enzymes,  and  to  identification  of  mutations  causing  disease.The  MPS  share  many  clinical  features,  although  in  variable  degrees.  These  include  a  chronic  and  progressive  course,  multisystem  involvement,  organomegaly,  dysostosis  multiplex,  and  abnormal  facies.  Hearing,  vision,  airway,  cardiovascular  function,  and  joint  mobility  may  be  affected.  Profound  mental  retardation  is  characteristic  of  MPS  IH  (Hurler  syndrome),  the  severe  form  of  MPS  II  (Hunter  syndrome),  and  all  subtypes  of  the  MPS  III  (Sanfilippo  syndrome),  but  normal  intellect  may  be  retained  in  other  MPS.  The  bony  lesions  of  MPS  IV  (Morquio  syndrome)  are  specific  to  that  disorder.  There  is  clinical  similarity  between  different  enzyme  deficiencies,  and,  conversely,  a  wide  spectrum  of  clinical  severity  within  any  one  enzyme  deficiency.  Supportive  management—with  particular  attention  to  respiratory  and  cardiovascular  complications,  loss  of  hearing  and  vision,  communicating  hydrocephalus,  and  spinal  cord  compression—can  greatly  improve  the  quality  of  life  for  patients  and  their  families.The  MPS  are  rare  diseases.  They  are  transmitted  in  an  autosomal  recessive  manner  except  for  MPS  II,  which  is  X-linked.  Mutations  underlying  any  one  MPS  are  very  heterogeneous,  but  one  or  a  few  mutant  alleles  may  predominate  in  specific  populations.  Most  are  point  mutations  or  small  changes  in  the  gene,  although  major  DNA  rearrangements  and  large  deletions  occur  in  MPS  II.  Correlation  of  disease  severity  with  genotype  is  sometimes  possible,  but  the  effect  of  missense  mutations  is  generally  difficult  to  predict.Enzyme  assays  are  available  for  diagnosis,  including  prenatal  diagnosis,  of  all  the  MPS.  Identification  of  heterozygotes  on  the  basis  of  enzyme  activity  is  generally  difficult  or  insufficiently  accurate.  Because  of  the  heterogeneity  of  mutations,  diagnosis  and  carrier  testing  by  DNA  analysis  requires  knowledge  of  the  mutant  alleles  in  the  family  under  consideration.There  are  numerous  animal  models  of  MPS.  In  addition  to  the  models  derived  from  mutations  that  have  occurred  naturally  in  dogs,  cats,  rats,  mice,  and  goats,  there  are  several  mouse  models  created  by  targeted  disruption  of  the  corresponding  mouse  gene.  The  biochemical  and  pathologic  features  of  these  animal  models  is  generally  quite  similar  to  those  of  their  human  counterparts,  but  the  clinical  presentations  may  be  milder.The  MPS  have  long  been  considered  potentially  amenable  to  therapy  by  exogenously  supplied  enzyme.  The  success  of  bone  marrow  transplantation  in  altering  the  course  of  some  ...
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/23
UR  - ommbid.mhmedical.com/content.aspx?aid=1181463720
ER  -