TY  - CHAP
M1  - Book, Section
TI  - Mucolipidosis Type IV
A1  - Goldin, Ehud
A1  - Slaugenhaupt, Susan A.
A1  - Smith, Janine A.
A1  - Schiffmann, Raphael
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  - Mucolipidosis  type  IV  (MLIV)  is  an  autosomal  recessive  inborn  error  of  intracellular  membrane  trafficking  that  is  associated  with  lysosomal  inclusions  in  a  variety  of  cell  types.  An  alteration  in  mucolipin-1,  a  transmembrane  protein  of  the  transient  receptor  potential  channel  family,  causes  MLIV.Most  of  the  patients  with  MLIV  have  severe  motor  developmental  delay,  corneal  clouding,  progressive  retinal  degeneration,  and  achlorhydria.  A  few  patients  are  less  severely  affected  and  exhibit  variable  general  developmental  delay,  ataxia,  and  dysarthria  together  with  the  characteristic  corneal  clouding  and  retinal  dystrophy.  Notably  absent  are  dysplastic  bone  abnormalities  and  enlargement  of  organs  such  as  the  liver  and  the  spleen.MLIV  is  pan-ethnic,  but  most  patients  are  of  Ashkenazi-Jewish  ancestry,  in  which  the  most  prevalent  mutation  occurs  at  a  frequency  of  approximately  1/100.The  mucolipidosis  type  IV  gene,  MCOLN1,  spans  12,300  base  pairs  on  chromosome  19p13.3  and  contains  14  exons.  The  product  of  this  gene  is  called  mucolipin-1,  a  580-amino-acid  protein  with  6  transmembrane  domains.  This  protein  is  thought  to  be  a  nonselective  cation  channel  or  a  calcium  channel,  but  its  exact  function  is  not  yet  completely  understood.Two  mutations,  g.5534A→G  and  g.511-6944del,  are  present  in  95%  of  all  Ashkenazi-Jewish  patients.  Population-based  screening  for  these  mutations  is  useful  for  the  identification  and  counseling  of  MLIV  carriers.  Identification  of  mutations  in  MCOLN1  should  be  used  for  prenatal  diagnosis.The  diagnosis  of  patients  suspected  of  having  MLIV  can  be  strengthened  by  the  finding  of  elevated  blood  gastrin.  A  skin  biopsy  showing  lysosomal  inclusions  in  almost  every  cell  type  can  assist  in  the  diagnosis.  Identifying  mutations  in  the  MCOLN1  gene  makes  the  definitive  diagnosis.There  is  no  specific  treatment  for  patients  with  MLIV.  A  comprehensive  rehabilitative  approach  can  significantly  improve  quality  of  life.  
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/24
UR  - ommbid.mhmedical.com/content.aspx?aid=1181453540
ER  -