Advertisement

Exon 2 deletion represents a common mutation in Turkish patients with fructose-1,6-bisphosphatase deficiency

  • Mustafa KılıçEmail author
  • Çiğdem Seher Kasapkara
  • Didem Yücel Yılmaz
  • Rıza Köksal Özgül
Original Article
  • 22 Downloads

Abstract

Fructose-1,6-bisphosphatase (FBPase) deficiency is an autosomal recessive inborn error of gluconeogenesis. We aimed to investigate clinical and biochemical findings and molecular genetic data in ten Turkish patients with fructose-1,6-bisphosphatase deficiency. Ten Turkish patients who were diagnosed with fructose-1,6-biphosphatase deficiency in a single center from 2013 to 2019 were included in this study. Their clinical and laboratory data were collected retrospectively. All patients were hospitalised in intensive care unit mostly after catabolic stress conditions such as infections, starvation and rarely fructose consumption. Prognosis was good after correct diagnosis and treatment. Molecular analyses of FBP1 gene revealed a homozygous exon 2 deletion in eight patients, a novel homozygous c.910_911dupTT mutation in one patient and a homozygous IVS5 + 1G > A splicing mutation in one patient. Exon 2 deletion (previously termed exon 1) was found to be the most common mutation in Turkish fructose-1,6-biphosphatase deficiency patients.

Keywords

Fructose-1,6-bisphosphatase deficiency FBP1 gene Fructose Hypoglycemia Coma Lactic acidosis 

Notes

Acknowledgements

We sincerely thank the family of the patient for their participation, after informed consent.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Afroze B, Yunus Z, Steinmann B, Santer R (2013) Transient pseudo-hypertriglyceridemia: a useful biochemical marker of fructose-1,6-bisphosphatase deficiency. Eur J Pediatr 172:1249–1253.  https://doi.org/10.1007/s00431-013-2084-6 CrossRefGoogle Scholar
  2. Baker L, Winegrad AI (1970) Fasting hypoglycaemia and metabolic acidosis associated with deficiency of hepatic fructose-1,6-diphosphatase activity. Lancet 2:13–16CrossRefGoogle Scholar
  3. Bhai P, Bijarnia-Mahay S, Puri RD, Saxena R, Gupta D, Kotecha U, Sachdev A, Gupta D, Vyas V, Agarwal D, Jain V, Bansal RK, Kumar TG, Verma IC (2018) Clinical and molecular characterization of Indian patients with fructose-1, 6-bisphosphatase deficiency: identification of a frequent variant (E281K). Ann Hum Genet 82:309–317.  https://doi.org/10.1111/ahg.12256 CrossRefGoogle Scholar
  4. Bulut D, Seker-Yilmaz B, Kor D, Ceylaner S, Ozgur-Horoz O, Onenli-Mungan N (2015) Fructose-1,6-bisphosphatase deficiency in early childhood: 5 Turkish cases (abstract). J Inherit Metab Dis 38(Suppl 1):179Google Scholar
  5. el-Maghrabi MR, Lange AJ, Jiang W, Yamagata K, Stoffel M, Takeda J, Fernald AA, le Beau MM, Bell GI, Baker L, Pilkis SJ (1995) Human fructose-1,6-bisphosphatase gene (FBP1): exon-intron organization, localization to chromosome bands 9q22.2-q22.3, and mutation screening in subjects with fructose-1,6-bisphosphatase deficiency. Genomics 27:520–525CrossRefGoogle Scholar
  6. Eren E, Edgunlu T, Abuhandan M, Yetkin I (2013) Novel fructose-1,6-bisphosphatase gene mutation in two siblings. DNA Cell Biol 32:635–639.  https://doi.org/10.1089/dna.2013.2119 CrossRefGoogle Scholar
  7. Erol S, Aydin B, Dilli D, Okumuş N, Zenciroğlu A, Gündüz M (2014) An interesting newborn case of fructose 1-6 diphosphatase deficiency triggered after thyme juice ingestion. Clin Lab 60:151–153Google Scholar
  8. Faiyaz-Ul-Haque M, Al-Owain M, Al-Dayel F, Al-Hassnan Z, Al-Zaidan H, Rahbeeni Z, Al-Sayed M et al (2009) Novel FBP1 gene mutations in Arab patients with fructose-1,6-bisphosphatase deficiency. Eur J Pediatr 168:1467–1471.  https://doi.org/10.1007/s00431-009-0953-9 CrossRefGoogle Scholar
  9. Gokcay G, Shin YS, Podskarbi T, Balci MC, Karaca M, Demirkol M (2015) Fructose-1,6-bisphosphatase deficiency: natural course of the disease with relavence to diagnosis and treatment in 23 patients (abstract). J Inherit Metab Dis 38(Suppl 1):179Google Scholar
  10. Herzog B, Morris AA, Saunders C, Eschrich K (2001) Mutation spectrum in patients with fructose-1,6-bisphosphatase deficiency. J Inherit Metab Dis 24:87–88CrossRefGoogle Scholar
  11. Ijaz S, Zahoor MY, Imran M, Ramzan K, Bhinder MA, Shakeel H, Igbal M et al (2017) Genetic analysis of fructose-1,6-bisphosphatase (FBPase) deficiency in nine consanguineous Pakistani families. J Pediatr Endocrinol Metab 30:1203–1210.  https://doi.org/10.1515/jpem-2017-0188 CrossRefGoogle Scholar
  12. Kato S, Nakajima Y, Awaya R, Hata I, Shigematsu Y, Saitoh S, Ito T (2015) 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 237:235–239.  https://doi.org/10.1620/tjem.237.235 CrossRefGoogle Scholar
  13. Kikawa Y, Inuzuka M, Jin BY, Kaji S, Yamamoto Y, Shigematsu Y, Nakai A, Taketo A, Ohura T, Mikami H, Mizunuma H, Suzuki Y, Narisawa K, Sudo M (1995) Identification of a genetic mutation in a family with fructose-1,6- bisphosphatase deficiency. Biochem Biophys Res Commun 210:797–804CrossRefGoogle Scholar
  14. Kikawa Y, Inuzuka M, Jin BY, Kaji S, Koga J, Yamamoto Y, Fujisawa K, Hata I, Nakai A, Shigematsu Y, Mizunuma H, Taketo A, Mayumi M, Sudo M (1997) Identification of genetic mutations in Japanese patients with fructose-1,6-bisphosphatase deficiency. Am J Hum Genet 61:852–861CrossRefGoogle Scholar
  15. Lebigot E, Brassier A, Zater M, Imanci D, Feillet F, Thérond P, de Lonlay P, Boutron A (2015) Fructose 1,6-bisphosphatase deficiency: clinical, biochemical and genetic features in French patients. J Inherit Metab Dis 38:881–887CrossRefGoogle Scholar
  16. Li N, Chang G, Xu Y, Ding Y, Li G, Yu T, Qing Y, Li J, Shen Y, Wang J, Wang X (2017) Clinical and molecular characterization of patients with Fructose1,6-Bisphosphatase deficiency. Int J Mol Sci 18(4). pii: E857).  https://doi.org/10.3390/ijms18040857
  17. Moey LH, Abdul Azize NA, Yakob Y, Leong HY, Keng WT, Chen BC, Ngu LH (2018) Fructose-1,6-bisphosphatase deficiency as a cause of recurrent hypoglycemia and metabolic acidosis: clinical and molecular findings in Malaysian patients. Pediatr Neonatol 59:397–403.  https://doi.org/10.1016/j.pedneo.2017.11.006 CrossRefGoogle Scholar
  18. Paksu MŞ, Kalkan G, Asilioglu N, Paksu S, Dinler G (2011) Gluconeogenesis defect presenting with resistant hyperglycemia and acidosis mimicking diabetic ketoacidosis. Pediatr Emerg Care 27:1180–1181.  https://doi.org/10.1097/PEC.0b013e31823b412d CrossRefGoogle Scholar
  19. Pinheiro FC, Sperb-Ludwig F, Ligabue-Braun R, Schüler-Faccini L, Fischinger Moura de Souza C, Vairo F, Schwartz IVD (2019) Genetic analyses of patients with fructose-1,6-bisphosphatase deficiency. Gene 699:102–109.  https://doi.org/10.1016/j.gene.2019.03.007
  20. Santer R, duMoulin M, Shahinyan T, Vater I, Maier E, Muntau AC, Steinmann B (2016) 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 11:44.  https://doi.org/10.1186/s13023-016-0415-1 CrossRefGoogle Scholar
  21. Steinmann B, Santer R (2016) Disorders of fructose metabolism) Disorders of Fructose Metabolism. In: Saudubray JM, Baumgartner MR, Walter J (eds) Inborn metabolic diseases, diagnosis and treatment, 6 th edn. Springer, Berlin, Heidelberg, pp 161–169CrossRefGoogle Scholar
  22. Tavil B, Sipahi T (2003) Fructose 1,6 diphosphatase deficiency in a Turkish infant. Eur J Pediatr 162:719–720CrossRefGoogle Scholar
  23. Visser G, Bakker HD, De Klerk JBC, Smeitink JAM, Simit GPA, Wijburg FA (2004) Natural history and treatment of fructose −1,6-diphosphatase deficiency in the Netherlands (abstract). J Inherit Metab Dis 27(Suppl 1):207Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Mustafa Kılıç
    • 1
    Email author
  • Çiğdem Seher Kasapkara
    • 1
  • Didem Yücel Yılmaz
    • 2
  • Rıza Köksal Özgül
    • 2
  1. 1.Metabolism UnitSami Ulus Children HospitalAnkaraTurkey
  2. 2.Institute of Child Health, Metabolism UnitHacettepe UniversityAnkaraTurkey

Personalised recommendations