TY  - CHAP
M1  - Book, Section
TI  - Galactosemia
A1  - Walter, John H.
A1  - Fridovich-Keil, Judith L.
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  main  sources  of  galactose  are  milk  and  milk  products.  Galactose  is  present  as  the  disaccharide  lactose,  but  lactose  is  hydrolyzed  to  its  constituent  monosaccharides  prior  to  absorption  from  the  intestine.  Galactose  is  an  essential  energy  source  in  infants  but  it  is  necessary  that  it  first  be  metabolized  to  glucose.  The  principal  pathway  for  the  metabolism  of  galactose  involves  three  enzymes:  galactokinase,  galactose-1-phosphate  uridyl  transferase,  and  uridine  diphosphate  galactose  4′-epimerase.  There  are  genetic  diseases  due  to  disorders  of  all  these  enzymes.The  biochemical  consequences  of  the  genetic  disorders  of  galactose  metabolism  are  abnormally  high  concentrations  of  galactose  and  its  metabolites  in  body  tissues  and  fluids.  The  clinical  consequences  range  from  life-threatening  crises  in  the  neonatal  period  and  severe  long-term  complications  to  complete  normality.The  first  enzyme  in  the  galactose  pathway  is  galactokinase.  The  gene  encoding  galactokinase  has  been  mapped  to  chromosome  17p24.  It  consists  of  8  exons  spanning  about  7.3  kb  of  genomic  DNA  and  shows  many  of  the  features  of  a  housekeeping  gene.  The  enzyme  is  a  monomer  containing  392  amino  acids  with  a  molecular  weight  of  42.The  main  clinical  feature  of  galactokinase  deficiency  is  cataracts  that  are  usually  bilateral  and  detectable  in  the  early  weeks  of  life,  although  they  have  been  observed  at  birth  and  in  a  fetus  at  20  weeks'  gestation.  Pseudotumor  cerebri  has  been  described  in  several  cases  of  galactokinase  deficiency  and  is  considered  to  be  a  true  consequence  of  the  disorder.  These  features  resolve  when  a  galactose-restricted  diet  is  introduced.The  gene  encoding  galactose-1-phosphate  uridyltransferase  is  located  on  the  short  arm  of  chromosome  9  in  the  p13  region  and  consists  of  11  exons.  The  cDNA  is  1295  bases  in  length  and  codes  a  polypeptide  of  379  amino  acids  and  an  estimated  molecular  weight  of  44.  The  active  enzyme  is  a  dimer  of  the  polypeptide.  More  than  200  base  changes  have  been  characterized  at  the  gene.  A  few  are  common,  but  most  are  rare;  the  distribution  of  several  mutations  has  been  studied  in  a  number  of  major  human  groups.  Q188R  is  the  most  common  in  Europe  and  in  individuals  of  European  descent.  S135L  is  found  almost  exclusively  in  individuals  of  African  descent.  In  vitro  functional  assays  demonstrate  that  not  all  mutations  at  the  GALT  locus  are  null.  In  vivo  assays  using  whole  body  galactose  oxidation  substantiate  these  findings.Severe  galactose-1-phosphate  uridyltransferase  deficiency  (classic  galactosemia)  presents  in  the  first  weeks  of  life  with  poor  feeding  and  weight  loss,  vomiting,  diarrhea,  lethargy,  and  hypotonia.  Liver  dysfunction,  bleeding  tendencies,  cataracts,  and  septicemia  may  be  found  on  examination.  These  features  usually  resolve  dramatically,  provided  treatment  is  started  early;  however,  it  is  now  recognized  that  a  number  of  affected  individuals  will  have  serious  long-term  complications,  possibly  as  a  result  of  continued  endogenous  galactose  production.The  human  uridine  diphosphate  galactose  4′-epimerase  gene  has  been  mapped  to  the  short  arm  of  chromosome  1  at  1p36.  The  gene  spans  4  kb  of  genomic  DNA  and  consists  of  11  exons  encoding  a  polypeptide  of  348  amino  acids  and  has  a  molecular  weight  of  38.  The  active  enzyme  is  a  dimer.  Several  mutations  ...
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/19
UR  - ommbid.mhmedical.com/content.aspx?aid=1181420964
ER  -