RT Book, Section
A1 Sly, William S.
A1 Shah, Gul N.
A2 Valle, David L.
A2 Antonarakis, Stylianos
A2 Ballabio, Andrea
A2 Beaudet, Arthur L.
A2 Mitchell, Grant A.
SR Print(0)
ID 1181475808
T1 The Carbonic Anhydrase II Deficiency Syndrome: Osteopetrosis with Renal Tubular Acidosis and Cerebral Calcification
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=1181475808
RD 2024/04/25
AB The  carbonic  anhydrase  II  deficiency  syndrome  is  an  autosomal  recessive  disorder  that  produces  osteopetrosis,  renal  tubular  acidosis,  and  cerebral  calcification.  Other  features  include  mental  retardation  (seen  in  over  90  percent  of  reported  cases),  growth  failure,  and  dental  malocclusion.Complications  of  osteopetrosis  include  increased  susceptibility  to  fractures  (which  do,  however,  heal  normally)  and  cranial  nerve  compression  symptoms.  Anemia  and  other  hematologic  manifestations  of  osteopetrosis  are  absent.The  renal  tubular  acidosis  is  usually  a  mixed  type.  A  distal  component  is  evident  from  inability  to  acidify  the  urine,  and  a  proximal  component  is  evident  from  a  lowered  transport  maximum  for  bicarbonate.  Impaired  respiratory  compensation  for  the  metabolic  acidosis  has  recently  been  recognized.Over  110  patients  have  been  reported,  all  of  who  have  a  quantitative  deficiency  of  carbonic  anhydrase  II  activity  and  immunoreactivity  in  erythrocytes.  Heterozygous  carriers  can  be  identified  by  simple  tests.  Structural  gene  mutations  have  been  identified  in  the  CA  II  gene  of  every  patient  analyzed  genetically.The  carbonic  anhydrase  II  gene  is  20  kb,  contains  seven  exons,  and  maps  to  chromosome  8q22.  Sixteen  distinct  mutations  have  been  identified  in  110  reported  patients.  Nearly  65  percent  of  affected  patients  are  homozygous  for  a  splice  junction  mutation  at  the  5′  end  of  exon  2.  Because  of  its  prevalence  among  families  of  Arabic  descent  from  Kuwait,  Saudi  Arabia,  and  North  Africa,  this  mutation  has  been  designated  the  “Arabic  mutation.”  The  second  recurrent  mutation,  a  frameshift  in  exon  7,  is  most  prevalent  in  Caribbean  Hispanic  populations.  The  third  recurrent  mutation  is  His  107  →  Tyr,  the  first  reported  mutation.  This  mutation  is  due  to  a  C  →  T  transition  in  exon  3  and  has  been  found  in  Belgian,  Italian,  Japanese,  and  American  patients.  The  three  affected  sisters  in  the  American  family  were  compound  heterozygotes,  having  inherited  the  His  107  →  Tyr  mutation  from  their  mother  and  a  splice  acceptor  mutation  in  the  3′  end  of  intron  5  from  their  father.  The  remaining  13  mutations  are  private  mutations  seen  in  single  families  and  all  are  detectable  by  PCR  amplification  and  direct  sequencing  of  various  exons.  Thus,  PCR-based  diagnosis  and  prenatal  diagnosis  are  available  for  the  16  known  mutations.Symptoms  of  metabolic  acidosis  improve  with  treatment,  but  no  specific  treatment  is  available.