TY  - CHAP
M1  - Book, Section
TI  - The Oculocerebrorenal Syndrome of Lowe (Lowe Syndrome)
A1  - Nussbaum, Robert L.
A1  - Suchy, Sharon F.
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  oculocerebrorenal  syndrome  of  Lowe  (OCRL)  is  a  multisystem  disorder  with  major  abnormalities  in  the  eyes,  the  nervous  system,  and  the  kidneys.  Prenatal  development  of  cataracts  is  universal,  and  other  ocular  abnormalities,  including  glaucoma,  microphthalmos,  decreased  visual  acuity,  and  corneal  keloid  formation,  are  frequent.  Neonatal  or  infantile  hypotonia,  intellectual  impairment,  and  areflexia  are  also  cardinal  features.  Mental  retardation,  although  very  common,  is  not  universal.  Stereotypic  behaviors,  including  tantrums  and  aggressiveness,  are  some  of  the  more  difficult  management  problems  in  the  disease.  Fanconi  syndrome  of  the  renal  tubule  (bicarbonaturia,  renal  tubular  acidosis,  aminoaciduria,  phosphaturia,  tubular  proteinuria,  and  impaired  urine-concentrating  ability)  is  also  a  major  feature,  but  the  severity  and  age  of  onset  of  the  tubular  dysfunction  are  variable.  Slowly  progressive  renal  failure  can  also  occur  in  the  second  to  fourth  decade  of  life.  Musculoskeletal  abnormalities  such  as  joint  hypermobility,  dislocated  hips,  and  fractures  may  develop  as  secondary  consequences  of  hypotonia  or  renal  tubular  acidosis  and  hypophosphatemia,  but  nontender  joint  swelling  and  subcutaneous  nodules  are  also  frequently  seen  and  may  reflect  a  primary  abnormality  of  excessive  connective  tissue  growth.OCRL  is  a  rare  X-linked  disorder  with  an  estimated  prevalence  of  only  a  few  cases  per  100,000  males.  The  only  significant  manifestation  in  carriers  is  in  the  lens  and  is  characterized  by  many  smooth,  off-white  micropunctate  cataracts  clustered  in  a  radial  wedge  pattern,  and,  occasionally,  a  dense  posterior  cortical  cataract.  The  sensitivity  of  carrier  detection  by  slit-lamp  exam  is  >90  percent  but,  as  with  most  X-linked  conditions,  penetrance  is  unlikely  to  ever  be  100  percent  in  female  carriers  because  the  proportion  of  cells  in  the  lens  that  have  an  inactivated  Lowe  syndrome  allele  can  vary  by  chance  between  carriers.  Germ  line  or  somatic  mosaicism  has  been  documented.The  gene  for  OCRL  (OCRL1),  termed  OCRL1,  located  at  Xq25-q26,  was  identified  by  positional  cloning  in  the  Xq25-q26  region  of  the  X  chromosome,  and  encodes  a  phosphatidylinositol  -4,5-  bisphosphate  5-phosphatase  (PtdIns-4,5-P2)  localized  to  the  Golgi  complex.  How  a  deficiency  of  this  enzyme  results  in  the  clinical  phenotype  remains  obscure.Clinical  diagnosis  of  OCRL  depends  on  the  cardinal  ophthalmologic,  neurologic,  and  renal  abnormalities,  while  X-linked  inheritance  is  extremely  helpful  when  present.  Carrier  detection  by  slit-lamp  examination  has  high  but  not  perfect  sensitivity.  Biochemical  assay  for  deficiency  of  PtdIns(4,5)P2  5-phosphatase  is  the  definitive  laboratory  test  for  diagnosing  patients  and  for  prenatal  diagnosis,  but  its  role  in  carrier  detection  is  unproved.Over  two  dozen  mutations  have  been  described  in  the  OCRL1  gene  in  Lowe  syndrome  patients.  Most  are  unique  to  a  family  and  are  either  nonsense  mutations  or  deletions  that  cause  frameshifts  and  premature  termination,  although  missense  mutations  in  domains  conserved  among  all  the  known  PtdIns(4,5)P2  5-phosphatases  are  also  seen.  Carrier  detection  can  be  done  by  direct  detection  of  mutations  when  known  and  by  linked  markers  when  the  mutation  is  unknown.Treatment  includes  cataract  extraction,  refraction  for  aphakia,  control  of  glaucoma,  speech  and  physical  therapy  for  developmental  delay,  anticonvulsants  or  behavior-modifying  medications  if  needed,  and  replacement  of  urinary  bicarbonate,  water,  and  phosphate  losses  if  indicated  by  the  development  of  acidosis  or  bone  disease.  
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/19
UR  - ommbid.mhmedical.com/content.aspx?aid=1184077191
ER  -