An Iranian Case with Fructose 1,6 Bisphosphatase Deficiency: A Case Report

Document Type : Case Report


1 Children Growth Disorder Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

2 Department of Pediatrics, Shahid Sadoughi Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

3 Mother and Newborn Health Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

4 Department of Biology, Faculty of Science, Yazd University, Yazd, Iran


Background: Deficiency of hepatic fructose 1,6 bisphosphatase (FBPase), a key enzyme in gluconeogenesis, impairs the formation of glucose from all gluconeogenic precursors including dietary fructose. Patients present with life threatening metabolic acidosis, fasting hypoglycemia, hepatomegaly, hyperketosis, elevated lactate and uric acid level. Glycerol and glycerol-3 phosphate have been found in the urine. The diagnosis of FBPase deficiency should be made by molecular analysis on DNA from peripheral leukocytes. The acute life threatening episodes should be treated with IV glucose at high rate and bicarbonate to control hypoglycemia and acidosis.
Case report: Here we reported a girl referred with anorexia, lethargy, recurrent vomiting, progressive respiratory distress, and hepatomegaly following respiratory viral infection. She also had a history of twice similar attacks but milder than previous episodes. The test results showed hypoglycemia and severe metabolic acidosis. Unfortunately, despite proper treatment, the patient died of pulmonary edema following a respiratory viral infection.
Conclusion: Once FBPase deficiency has been diagnosed and adequate management introduced, its course is usually benign. Growth and both psychomotor and intellectual development are unimpaired and tolerance to fasting improves with age.


  1. Sugita G, Tsuyoshi H, Nishijima K, Yoshida Y. Fructose-1,6-Bisphosphatase Deficiency: A Case of a Successful Pregnancy by Closely Monitoring Metabolic Control. JIMD Rep [Internet]. 2014 [cited 2022 May 30];14:115. Available from: /pmc/articles/PMC4213334/
  2. Moey LH, Abdul Azize NA, Yakob Y, Leong HY, Keng WT, Chen BC, et al. Fructose-1,6-bisphosphatase deficiency as a cause of recurrent hypoglycemia and metabolic acidosis: Clinical and molecular findings in Malaysian patients. 2018 Aug 1;59(4):397–403.
  3. Salih RM, Mohammed EA, Alhashem AM, Mohamed S, Al-Aqeel AI. Fructose-1,6-bisphosphatase deficiency with confirmed molecular diagnosis: An important cause of hypoglycemia in children. Saudi Med J [Internet]. 2020 Feb 1 [cited 2022 Jun 7];41(2):199. Available from: /pmc/articles/PMC7841638/
  4. Ayman W. El-Hattab. Inborn Errors of Metabolism [Internet]. 2015 [cited 2022 Jun 7]. 413–440 p. Available from: Congenitos Metabolismo/El-Hattab.Errorescongenitosmetabolismo.ClinicsPerinatology.Junio2015.pdf
  5. Robert M. Kliegman & Joseph St. Geme. Nelson Textbook of Pediatrics, 2-Volume Set - 9780323529501 [Internet]. 21th ed. 2020 [cited 2022 Jun 6]. 792 p. Available from:
  6. Bijarnia-Mahay S, Bhatia S, Arora V. Fructose-1,6-Bisphosphatase Deficiency. GeneReviews® [Internet]. Dec [cited 2022 May 30]; Available from:
  7. Kyriakie Sarafoglou, Georg F. Hoffmann KSR. Pediatric Endocrinology and Inborn Errors of Metabolism, 2e | AccessPediatrics | McGraw Hill Medical [Internet]. second. 2017 [cited 2022 Jun 6]. 103–104 p. Available from:
  8. Kato S, Nakajima Y, Awaya R, Hata I, Shigematsu Y, Saitoh S, et al. Pitfall in the diagnosis of fructose-1,6-bisphosphatase deficiency: Difficulty in detecting glycerol-3-phosphate with solvent extraction in urinary GC/MS analysis. Tohoku J Exp Med. 2015 Nov 6;237(3):235–9.
  9. Olpin SE. The metabolic investigation of sudden infant death. Ann Clin Biochem [Internet]. 2004 Jul [cited 2022 Jan 8];41(Pt 4):282–93. Available from:
  10. Santer R, Du Moulin M, Shahinyan T, Vater I, Maier E, Muntau AC, et al. A summary of molecular genetic findings in fructose-1,6-bisphosphatase deficiency with a focus on a common long-range deletion and the role of MLPA analysis. Orphanet J Rare Dis [Internet]. 2016 Apr 21 [cited 2022 May 30];11(1):1–7. Available from:
  11. Cao J PJ. Fructose-1,6-bisphosphatase deficiency: A pediatric case report. Pediatr Neonatol [Internet]. 2022 [cited 2022 May 30];63(2):204–5. Available from:
  12. William L. Nyhan MP, Georg F. Hoffmann M. Atlas of Inherited Metabolic Diseases [Internet]. fourth. 2020 [cited 2022 Jun 6]. 371–373 p. Available from:

Articles in Press, Accepted Manuscript
Available Online from 30 June 2022
  • Receive Date: 30 June 2022
  • Accept Date: 30 June 2022
  • First Publish Date: 30 June 2022