TY  - CHAP
M1  - Book, Section
TI  - The Renal Fanconi Syndrome
A1  - Bergeron, Michel
A1  - Gougoux, André
A1  - Noël, Josette
A1  - Parent, Lucie
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  renal  Fanconi  syndrome  consists  of  two  components:  (a)  a  generalized  dysfunction  of  the  proximal  renal  tubule  leading  to  impaired  proximal  reabsorption  of  amino  acids,  glucose,  phosphate,  urate,  and  bicarbonate  and  therefore  increased  urinary  excretion  of  all  these  solutes,  and  (b)  a  vitamin  D–resistant  metabolic  bone  disease—either  rickets  in  growing  children  or  osteomalacia  in  adults.The  renal  Fanconi  syndrome  is  either  associated  with  various  inborn  errors  of  metabolism  or  acquired  through  exposure  to  various  toxic  agents.  The  inherited  form  may  be  idiopathic  (in  the  absence  of  any  recognizable  metabolic  disease)  or  secondary  to  various  primary  Mendelian  diseases.  Cystinosis  is  the  most  common  cause  of  a  secondary  hereditary  Fanconi  syndrome  in  children.  The  degree  of  cystine  accumulation  determines  three  clinical  forms  of  cystinosis:  infantile,  adolescent,  and  adult.  The  secondary  Fanconi  syndrome  disappears  in  patients  with  hereditary  fructose  intolerance,  galactosemia,  tyrosinemia,  and  Wilson  disease  when  these  disorders  are  treated  by  restriction  of  fructose,  galactose,  tyrosine,  or  copper,  respectively.  Other  metabolic  diseases  also  can  be  associated  with  the  Fanconi  syndrome:  vitamin  D  dependency,  glycogen  storage  disease,  and  oculocerebrorenal  (Lowe)  syndrome.A  wide  variety  of  toxic  and  immunologic  tubular  injuries  may  produce  the  generalized  renal  dysfunction  characteristic  of  the  Fanconi  syndrome.  Heavy  metals  (cadmium,  uranium,  mercury,  lead,  and  platinum),  various  drugs  (especially  antibiotics),  the  glomerular  filtration  of  abnormal  proteins  observed  in  dysproteinemias,  and  immunologic  disorders  are  all  known  to  induce  a  Fanconi  syndrome.  Maleate  and  cadmium  were  used  to  produce  experimental  models  in  animals.  Finally,  the  Basenji  dog  can  have  a  spontaneous  Fanconi  syndrome.The  renal  Fanconi  syndrome  theoretically  may  result  either  from  multiple  transport  dysfunctions  restricted  to  the  proximal  tubule  or  from  concomitant  proximal  and  distal  tubular  dysfunctions.  Recent  data  obtained  from  the  experimental  Fanconi  syndrome  indicate  that  the  initial  deleterious  effect  of  maleate  (and  other  toxins)  in  the  proximal  cells  could  be  via  megalin,  a  membrane  glycoprotein  that  is  a  receptor  for  many  ligands.  Blockade  at  any  point  along  the  recycling  pathway  will  modify  luminal  membrane  function  of  the  proximal  tubular  cells  by  trapping  transport  proteins  and  other  constituents  in  endosomes.  Some  experimental  data  suggest  that  in  addition  to  the  proximal  disturbance,  a  distal  nephron  involvement  may  play  a  role  in  the  final  production  of  the  aminoaciduria,  glycosuria,  and  phosphaturia  observed  in  the  Fanconi  syndrome;  all  these  transport  defects  could  result  from  a  decreased  entry  of  molecules  into  the  cell,  an  increased  backflux  at  its  luminal  pole,  or  a  combination  of  both.  An  impaired  mitochondrial  production  of  ATP  and  a  reduced  activity  of  the  basolateral  membrane  Na+,  K+-ATPase  also  have  been  suggested  as  pathogenetic  mechanisms.  The  presence  of  physiologic  intracellular  gradients  of  Na+,  ATP,  and  ADP  may  amplify  a  minor  decrease  in  mitochondrial  phosphorylation  and  translate  a  modest  defect  in  energy  production  into  a  major  transport  dysfunction.In  children,  the  clinical  features  of  the  renal  Fanconi  syndrome  are  not  specific  and  result  from  the  renal  loss  of  fluid  and  electrolytes  and  the  characteristic  vitamin  D–resistant  metabolic  bone  disease.  The  most  frequent  manifestations  are  polyuria,  polydipsia,  dehydration,  hypokalemia,  acidosis,  impaired  growth,  and  rickets.  In  the  absence  of  a  specific  ...
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/19
UR  - ommbid.mhmedical.com/content.aspx?aid=1181473458
ER  -