TY  - CHAP
M1  - Book, Section
TI  - Aminoacylase I Deficiency
A1  - van Coster, Rudy
A2  - Valle, David L.
A2  - Antonarakis, Stylianos
A2  - Ballabio, Andrea
A2  - Beaudet, Arthur L.
A2  - Mitchell, Grant A.
Y1  - 2019
N1  - 10.1036/ommbid.268
T2  - The Online Metabolic and Molecular Bases of Inherited Disease
AB  - Aminoacylase  I  (EC  3.5.1.14)  is  a  homodimeric  zinc-binding  metalloenzyme  located  in  the  cytosol  involved  in  the  hydrolysis  of  N-acylated  and  N-acetylated  amino  acids,  except  L-aspartate.Aminoacylase  I  needs  to  be  differentiated  from  other  acylases  with  diverse  substrate  specificities  identified  in  mammalian  tissues,  including  aminoacylase  II  (aspartoacylase)  (EC  3.5.1.15),  aryl  acylamidase  (EC  3.5.1.13),  and  ε-acyllysine  acylase  (EC  3.5.1.17).Aminoacylase  II  (aspartoacylase)  cleaves  the  N-acetylated  derivative  of  aspartate  but  no  other  N-acetyl  amino  acids.  This  enzyme  is  deficient  in  Canavan  disease  (Aspartoacylase  Deficiency  (Canavan  Disease)).  In  the  affected  patients,  increased  concentrations  of  N-acetyl-aspartate  can  be  detected  in  the  brain  by  nuclear  magnetic  resonance  (NMR)  spectroscopy.  In  the  cerebral  white  matter,  abnormal  signals  are  seen  on  magnetic  resonance  imaging  (MRI).  The  clinical  characteristics  of  patients  with  aminoacylase  II  deficiency  are  different  from  those  seen  in  patients  with  aminoacylase  I  deficiency.In  the  urine  of  the  patients  with  aminoacylase  I  deficiency,  an  increased  excretion  of  several  N-acetylated  amino  acids,  including  the  derivatives  of  serine,  glutamic  acid,  alanine,  methionine,  glycine,  leucine,  and  valine,  can  be  detected  by  gas  chromatographic-mass  spectrometric  (GC-MS)  and/or  MR  spectroscopy.  Epstein-Barr  virus  (EBV)-transformed  lymphoblasts  can  be  used  for  measurement  of  enzyme  activity.Eleven  patients  have  now  been  reported  with  aminoacylase  I  deficiency.The  first  patient  was  reported  by  Van  Coster  et  al.  This  patient  presented  in  the  neonatal  period  with  signs  of  an  acute  encephalopathy.  Cerebral  MRI  showed  abnormal  signals  in  the  cortico-subcortical  zones  consistent  with  cortical  laminar  necrosis.  A  repeat  cerebral  MRI  at  the  age  of  four  months  showed  mild  signs  of  cerebral  cortical  atrophy.  At  six  months  of  age,  psychomotor  development  was  within  normal  limits  and  clinical  neurological  examination  was  normal.  During  the  following  years,  the  patient  had  developed  a  severe  autism  spectrum  disorder.  Ten  additional  patients  have  been  reported  since  then  (Sass  et  al.16,  Sass  et.17,  Tylki-Szymanska  et  al.19,  Calvin  et  al.2).  Their  clinical  presentation  was  heterogeneous.  Four  of  the  eleven  reported  patients  suffered  from  an  autism  spectrum  disorder  and/or  delay  in  speech  and  language  development,  three  had  moderate  to  severe  developmental  delay,  and  four  had  normal  cognitive  development  (two  of  them  had  neurological  complications).  Two  were  reported  to  be  asymptomatic.At  this  moment  it  is  not  clear  whether  aminoacylase  I  deficiency  represents  a  true  metabolic  disorder  with  a  causal  relationship  between  the  enzyme  defect  and  the  clinical  phenotype,  or  whether  it  confers  a  risk  for  developmental  delay  with  speech  retardation  and  autism.  There  is  a  possibility  that  it  is  only  an  abnormal  biochemical  finding  without  any  clinical  neurological  involvement.Aminoacylase  I  is  encoded  by  ACY1,  an  evolutionarily  conserved  gene  located  on  the  short  arm  of  chromosome  3  (3p21.1).  It  has  an  open  reading  frame  of  1224  bp  coding  for  a  protein  408  amino  acids  long  with  a  predicted  molecular  mass  of  45,882  Da.  Different  mutations  have  been  detected  in  aminoacylase  1-deficient  probands.  The  missense  allele  (R353C)  is  the  most  common  mutation.  This  mutation  was  also  found  on  five  of  161  and  one  of  210  normal  chromosomes  in  two  different  studies.N-terminal  blocking  of  proteins  is  a  widespread  phenomenon  in  eukaryotic  cells.  Approximately  50  to  80%  of  all  ...
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
M3  - doi: 10.1036/ommbid.268
Y2  - 2024/04/16
UR  - ommbid.mhmedical.com/content.aspx?aid=1181479486
ER  -