RT Book, Section
A1 Steinmann, Beat
A1 Gitzelmann, Richard
A1 Van den Berghe, Georges
A2 Valle, David L.
A2 Antonarakis, Stylianos
A2 Ballabio, Andrea
A2 Beaudet, Arthur L.
A2 Mitchell, Grant A.
SR Print(0)
ID 1181420363
T1 Disorders of Fructose Metabolism
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=1181420363
RD 2024/04/19
AB Fructose  is  an  important  source  of  dietary  carbohydrates.  In  Western  societies,  daily  intake  by  adults  is  presently  approximately  100  g.  The  liver,  kidney,  and  small  intestine  are  the  main  sites  of  fructose  metabolism,  but  adipose  tissue  also  participates.  Fructose,  given  intravenously  in  high  doses,  is  clearly  toxic  and  causes  hyperuricemia,  hyperlactatemia,  and  ultrastructural  alterations  in  liver  and  intestinal  cells.Essential  fructosuria,  an  autosomal-recessive  disorder,  is  a  benign,  asymptomatic  metabolic  anomaly  caused  by  the  absence  of  fructokinase.  Alimentary  hyperfructosemia  and  fructosuria  are  the  principal  signs.  Despite  the  interruption  of  the  specific  fructose  pathway,  up  to  nine  tenths  of  the  administered  fructose  is  retained  by  fructokinase-deficient  subjects.Hereditary  fructose  intolerance,  an  autosomal-recessive  disorder,  is  characterized  by  severe  hypoglycemia  and  vomiting  shortly  after  the  intake  of  fructose.  Prolonged  fructose  ingestion  in  infants  leads  to  poor  feeding,  vomiting,  hepatomegaly,  jaundice,  hemorrhage,  proximal  renal  tubular  syndrome,  and  finally,  hepatic  failure  and  death.  Patients  develop  a  strong  distaste  for  noxious  food.  Therefore,  a  chronic  course  is  observed  only  in  preschool-aged  children.  Fructaldolase  B  of  liver,  kidney  cortex,  and  small  intestine  is  deficient.  Hypoglycemia  after  fructose  ingestion  is  caused  by  fructose  1-phosphate–inhibiting  glycogenolysis  at  the  phosphorylase  level  and  gluconeogenesis  at  the  mutant  aldolase  level.  Patients  remain  healthy  on  a  fructose-  and  sucrose-free  diet.  The  severity  of  the  disease  phenotype  appears  to  be  independent  of  the  nature  of  the  aldolase  B  gene  mutations  so  far  identified.Hereditary  fructose  1,6-bisphosphatase  deficiency,  an  autosomal-recessive  disorder,  is  characterized  by  episodic  spells  of  hyperventilation,  apnea,  hypoglycemia,  ketosis,  and  lactic  acidosis,  with  a  precipitous  and  often  lethal  course  in  the  newborn  infant.  Later  episodes  are  often  triggered  by  fasting  and  febrile  infections.  Due  to  the  enzyme  defect,  gluconeogenesis  is  severely  impaired.  Gluconeogenic  precursors  such  as  amino  acids,  lactate,  and  ketones  accumulate  as  soon  as  liver  glycogen  stores  are  depleted.  Patients  do  not  vomit  after  fructose  intake,  and  aversion  to  sweets  does  not  develop.  Their  tolerance  to  fasting  grows  with  age.  Patients  past  early  childhood  seem  to  develop  normally.D-glyceric  aciduria,  erythrocyte  aldolase  deficiency,  and  incomplete  fructose  absorption  are  briefly  mentioned.