eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases

Fructose 1-Phosphate Aldolase Deficiency (Fructose Intolerance): Differential Diagnoses & Workup

Author: Karl S Roth, MD, Professor and Chair, Department of Pediatrics, Creighton University School of Medicine
Contributor Information and Disclosures

Updated: Mar 24, 2009

Workup

Laboratory Studies

  • Based on the thorough dietary history of an ill child, the most straightforward approach to diagnosis of fructose 1-phosphate aldolase deficiency is to demonstrate the presence of a non–glucose-reducing sugar in the urine. This is readily accomplished with Clinitest. Then, if test results are positive, thin-layer chromatographic separation should be used for confirmation.
  • Urine metabolic screening results may also provide evidence of glucosuria, proteinuria, and aminoaciduria, all of which are part of renal Fanconi syndrome.
  • Plasma electrolyte levels are important to determine, because the renal tubular acidosis component of hereditary fructose intolerance (HFI) may significantly depress the total plasma bicarbonate level.
  • Obtain liver function test results to assess the degree of hepatocellular disease.

Other Tests

  • Elimination of dietary fructose is both a compulsory and therapeutic step. In patients who are ill, elimination may also serve as a diagnostic test because all symptoms should completely resolve.
  • Only asymptomatic patients in a controlled setting should undergo intravenous fructose tolerance testing; do not use oral fructose tolerance testing because of the potentially violent GI response.
  • The combination of a therapeutic response to fructose elimination and a positive response to the fructose tolerance test is sufficient to exclude obtaining a biopsy sample. However, a molecular analysis in leucocytes of the gene on chromosome 9 may provide definitive evidence of a mutation at the q22.3 band.

Histologic Findings

  • In a liver biopsy specimen from an untreated patient, evidence of hepatocellular involvement is clear, including areas of focal necrosis, fatty degeneration in peripheral lobules, bile duct proliferation, and late changes of portal and biliary cirrhosis.
  • Histologic changes are much less striking in the kidney and intestine, the other tissues with aldolase-B deficiency.
  • The kidney may demonstrate granulation of the proximal tubular epithelium with some tubule dilatation.
  • The intestine may show small areas of hemorrhage in the submucosa or serosa.
  • Except in untreated patients with cirrhosis late in the course of disease, all of the above changes are reversible. Of note, the availability of molecular analysis of the gene defect obviates the need for a corroborative biopsy sample.

More on Fructose 1-Phosphate Aldolase Deficiency (Fructose Intolerance)

Overview: Fructose 1-Phosphate Aldolase Deficiency (Fructose Intolerance)
Differential Diagnoses & Workup: Fructose 1-Phosphate Aldolase Deficiency (Fructose Intolerance)
Treatment & Medication: Fructose 1-Phosphate Aldolase Deficiency (Fructose Intolerance)
Follow-up: Fructose 1-Phosphate Aldolase Deficiency (Fructose Intolerance)
Multimedia: Fructose 1-Phosphate Aldolase Deficiency (Fructose Intolerance)
References
[ CLOSE WINDOW ]

References

  1. Santer R, Rischewski J, von Weihe M, Niederhaus M, Schneppenheim S, Baerlocher K, et al. The spectrum of aldolase B (ALDOB) mutations and the prevalence of hereditary fructose intolerance in Central Europe. Hum Mutat. Jun 2005;25(6):594. [Medline].

  2. Tsampalieros A, Beauchamp J, Boland M, Mack DR. Dietary fructose intolerance in children and adolescents. Arch Dis Child. Dec 2008;93(12):1078. [Medline].

  3. Gomara RE, Halata MS, Newman LJ, et al. Fructose intolerance in children presenting with abdominal pain. J Pediatr Gastroenterol Nutr. Sep 2008;47(3):303-8. [Medline].

  4. Tolan DR. Molecular basis of hereditary fructose intolerance: mutations and polymorphisms in the human aldolase B gene. Hum Mutat. 1995;6(3):210-8. [Medline].

  5. Michelakakis H, Moraitou M, Mavridou I, Dimitriou E. Plasma lysosomal enzyme activities in congenital disorders of glycosylation, galactosemia and fructosemia. Clin Chim Acta. Mar 2009;401(1-2):81-3. [Medline].

  6. Ali M, Rellos P, Cox TM. Hereditary fructose intolerance. J Med Genet. May 1998;35(5):353-65. [Medline].

  7. Chambers RA, Pratt RTC. Idiosyncrasy to fructose. Lancet. 1956;2:340.

  8. Froesch ER, Prader A, Labhart A, Stuber HW, Wolf HP. Die hereditare Fructoseintoleranz, eine bisher nicht bekannte kongenitale Stoffwechselstorung. Schweiz Med Wochenschr. 1957;87:1168-1171.

  9. Froesch ER, Wolf HP, Baitsch H, Prader A, Labhart A. Hereditary fructose intolerance. An inborn defect of hepatic fructose-1-phosphate splitting aldolase. Am J Med. Feb 1963;34:151-67. [Medline].

  10. Levin B, Oberholzer VG, Snodgrass GJAI, Stimmler L, Wilmers MJ. Fructosaemia. An inborn error of fructose metabolism. Arch Dis Child. Jun 1963;38:220-30. [Medline].

  11. Mass RE, Smith WR, Walsh JR. The association of hereditary fructose intolerance and renal tubular acidosis. Am J Med Sci. May 1966;251(5):516-23. [Medline].

  12. Muller P, Meier C, Bohme HJ. Fructose breath hydrogen test - is it really a harmless diagnostic procedure?. Dig Dis. 2003;21:276-278.

  13. Perheentupa J, Raivio K. Fructose-induced hyperuricaemia. Lancet. Sep 9 1967;2(7515):528-31. [Medline].

  14. Steinmann B, Gitzelmann R. The diagnosis of hereditary fructose intolerance. Helv Paediatr Acta. Sep 1981;36(4):297-316. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

fructose 1-phosphate aldolase deficiency, hereditary fructose intolerance, HFI, fructosemia, fructose 1,6-bisphosphate aldolase B deficiency, aldolase B deficiency, F-1-P, vomiting, hypoglycemia, failure to thrive, cachexia, hepatomegaly, jaundice, coagulopathy, severe metabolic acidosis, lactic acidosis, coma, renal Fanconi syndrome, hyperuricemia, lactic acidemia, proximal tubular acidosis, aminoaciduria, glucosuria, phosphaturia, renal tubular acidosis, non–glucose-reducing sugar, elimination of fructose, dietary history, renal tubule dysfunction

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Karl S Roth, MD, Professor and Chair, Department of Pediatrics, Creighton University School of Medicine
Karl S Roth, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Nutrition, American Pediatric Society, American Society for Clinical Nutrition, American Society of Nephrology, Association of American Medical Colleges, Medical Society of Virginia, New York Academy of Sciences, Sigma Xi, Society for Pediatric Research, and Southern Society for Pediatric Research
Disclosure: Nothing to disclose.

Medical Editor

Michael Fasullo, PhD, Senior Scientist, Ordway Research Institute; Associate Professor, State University of New York at Albany; Adjunct Associate Professor, Center for Immunology and Microbial Disease, Albany Medical College
Michael Fasullo, PhD is a member of the following medical societies: Radiation Research Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

David Flannery, MD, FAAP, FACMG, Vice Chair of Education, Chief, Section of Medical Genetics, Professor, Department of Pediatrics, Medical College of Georgia
David Flannery, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics and American College of Medical Genetics
Disclosure: Nothing to disclose.

CME Editor

Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System
Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD, Professor, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics and Rehabilitation, University of Nebraska Medical Center
Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.