RT Book, Section
A1 Johnson, Jean L.
A1 Duran, Marinus
A2 Valle, David L.
A2 Antonarakis, Stylianos
A2 Ballabio, Andrea
A2 Beaudet, Arthur L.
A2 Mitchell, Grant A.
SR Print(0)
ID 1181452165
T1 Molybdenum Cofactor Deficiency and Isolated Sulfite Oxidase Deficiency
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=1181452165
RD 2024/04/18
AB The  molybdenum  cofactor  is  a  low-molecular-weight  prosthetic  group  in  which  the  metal  is  complexed  to  a  unique  pterin  species  termed  molybdopterin.  The  cofactor  is  essential  for  the  function  of  the  human  enzymes  sulfite  oxidase,  xanthine  dehydrogenase,  and  aldehyde  oxidase.  Patients  with  molybdenum  cofactor  deficiency  (MIM  252150  and  252150)  are  deficient  in  the  activity  of  all  three  enzymes  and  exhibit  symptoms  that  include  severe  neurologic  abnormalities,  dislocated  ocular  lenses,  and  mental  retardation.  They  excrete  elevated  levels  of  sulfite,  thiosulfate,  S-sulfocysteine,  taurine,  xanthine,  and  hypoxanthine  and  low  amounts  of  uric  acid.  Patients  with  isolated  sulfite  oxidase  deficiency  (MIM  272300)  lack  sulfite  oxidase  activity  but  are  normal  with  respect  to  molybdenum  cofactor  and  xanthine  dehydrogenase  and  aldehyde  oxidase  functions.  This  form  of  sulfite  oxidase  deficiency  produces  clinical  symptoms  and  neuropathology  essentially  indistinguishable  from  those  of  the  combined  deficiency  disease.More  than  100  patients  have  been  diagnosed  with  molybdenum  cofactor  deficiency  or  isolated  sulfite  oxidase  deficiency.  Molybdenum  cofactor  deficiency  appears  to  be  more  prevalent  than  the  isolated  deficiency  but  is  also  more  likely  to  be  detected  in  routine  screening  programs.  Patients  with  milder  clinical  symptoms  and  late  onset  are  found  more  often  among  those  with  isolated  sulfite  oxidase  deficiency.  Both  molybdenum  cofactor  deficiency  and  isolated  sulfite  oxidase  deficiency  are  inherited  as  autosomal  recessive  traits,  with  obligate  heterozygotes  displaying  no  symptoms.  Patients  belong  to  a  variety  of  ethnic  groups  and  are  found  among  the  populations  of  Europe,  North  America,  Northern  Africa,  Turkey,  and  Asia.Although  considerable  variability  in  severity  of  symptoms  and  age  of  onset  does  occur,  the  key  clinical  symptom  for  molybdenum  cofactor  deficiency  and  isolated  sulfite  oxidase  deficiency  is  severe  convulsions,  presenting  early  after  birth.  All  patients  with  this  presentation  immediately  should  be  subjected  to  metabolic  screening  procedures.  Many  patients  display  dysmorphic  facial  features  that  resemble  those  in  patients  with  perinatal  asphyxia.  Patients  with  this  presentation  and  no  apparent  hypoxic  event  at  birth  should  be  screened  for  these  disorders.Pathology  studies  in  a  number  of  cases  of  molybdenum  cofactor  deficiency  and  isolated  sulfite  oxidase  deficiency  have  revealed  a  severe  encephalopathy  with  marked  neuronal  loss  and  demyelination  in  the  white  matter  accompanied  by  gliosis  and  diffuse  spongiosis.  The  observation  that  neither  isolated  xanthinuria  nor  a  combined  loss  of  xanthine  dehydrogenase  and  aldehyde  oxidase  results  in  encephalopathy  supports  the  conclusion  that  these  effects  result  from  the  absence  of  sulfite  oxidase  activity.  A  disturbed  development  and  damage  to  the  brain  may  occur  as  a  result  of  accumulation  of  toxic  levels  of  sulfite  in  cerebro.Prenatal  diagnosis  of  molybdenum  cofactor  deficiency  and  of  isolated  sulfite  oxidase  deficiency  is  accomplished  by  assay  of  sulfite  oxidase  activity  in  uncultured  chorionic  villus  tissue  or  in  cultured  amniotic  cells.Molybdenum  cofactor  deficiency  and  isolated  sulfite  oxidase  deficiency  are  serious  and  often  fatal  diseases  for  which  no  effective  therapy  is  generally  available.  Some  patients,  especially  those  with  milder  forms  of  isolated  sulfite  oxidase  deficiency,  respond  well  to  the  administration  of  diets  low  in  sulfur-containing  amino  acids.  Some  success  in  seizure  control  has  been  achieved  with  the  antiepileptic  drug  vigabatrin.The  genes  for  sulfite  oxidase  and  for  most  of  the  molybdenum  ...