Journal of The Korean Society of Inherited Metabolic disease (대한유전성대사질환학회지)

The Korea Society of Inherited Metabolic Disease (대한유전성대사질환학회)
권호 표지

Clinical and Laboratory Characteristics of Galactokinase Hyperactivity

GALK Hyperactivity로 인한 갈락토스혈증의 임상적 특성에 관한 연구

  • Yang, Seung Do (Department of Pediatrics, College of Medicine, Soonchunhyang University, Bucheon Hospital) ;
  • Lee, Jungho (Department of Pediatrics, College of Medicine, Soonchunhyang University, Seoul Hospital) ;
  • Shin, Young Lim (Department of Pediatrics, College of Medicine, Soonchunhyang University, Bucheon Hospital) ;
  • Lee, Dong Hwan (Department of Pediatrics, College of Medicine, Soonchunhyang University, Seoul Hospital) ;
  • Hong, Yong Hee (Department of Pediatrics, College of Medicine, Soonchunhyang University, Bucheon Hospital)
  • 양승도 (순천향대학교 부천병원 소아청소년과) ;
  • 이정호 (순천향대학교 서울병원 소아청소년과) ;
  • 신영림 (순천향대학교 부천병원 소아청소년과) ;
  • 이동환 (순천향대학교 서울병원 소아청소년과) ;
  • 홍용희 (순천향대학교 부천병원 소아청소년과)
  • Published : 2016.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: Galactose is metabolized to galactose-1-phosphate by galactokinase (GALK), galactose-1-phosphate uridyltransferase (GALT) and UDP-galactose-4-epimerase (GALE), and galactosemia occurs when each enzyme is deficient. In Korea, unlike foreign countries, classic galactosemia is rare and transient galactosemia due to GALK hyperactivity is reported, but studies on frequency, clinical significance, and genetic variation are lacking. In this study, we analyzed the clinical characteristics of patients with galactosemia due to GALK hyperactivity. Methods: We investigated 85 patients who had an elevated galactose level in the neonatal screening test without deficiency of enzymes at Department of Pediatrics, Seoul & Bucheon Soonchunhyang University Hospital from January 2008 to June 2016. We investigated the level of galactose, galactose-1-phosphate, GALK and duration of galactose normalization, and analyzed the correlation between GALK elevation and galactose, galactose-1-phosphate and duration of galactose normalization. And the levels of galactose, galactose-1-phosphate, and duration of galactose normalization were compared between the galactose-free formula feeding group and non-feeding group. Results: Mean age of visit was $26.7{\pm}16.1days$. Duration of galactose normalization was $35.3{\pm}20.5days$. Mean galactose level was $18.5{\pm}7.3mg/dL$ in the neonatal screening and follow-up galactose level in serum was $2.3{\pm}5.4mg/dL$. The mean value of galactose-1-phosphate was $6.0{\pm}4.7mg/dL$ and the mean GALK level was $3.84{\pm}1.28{\mu}mol/Hr/gHb$. There was no significant correlation between GALK levels and galactose levels in the neonatal screening test (P=0.351), and we analyzed the correlation between GALK levels and follow-up galactose levels in serum, there was no significant correlation (P=0.101). There was a significant correlation between GALK levels and galactose-1-phosphate (P=0.015), and the correlation between GALK levels and duration of galactose normalization was not statistically significant (P=0.176). 49% of the patients were fed galactose-free formula, and 45% were not. Galactose and galactose-1-phosphate levels in the neonatal screening test were statistically significantly higher (P=0.004, 0.034) in using galactose-free formula group. Duration of galactose normalization was not related to the use of galactose-free formula (P=0.266, 0.249). Conclusion: Galactosemia due to GALK hyperactivity seems to be a temporary phenomenon and may not require galactose restriction. More research is needed on the role of the nuclear protein, racial traits and genetic variations in Korean patients.

Keywords

References

  1. Cuthbert C, Klapper H, Elsas L. Diagnosis of inherit disorders of galactose metabolism. Curr Protoc Hum Genet 2008; Unit 17.5
  2. Hazel M. Holden, Ivan R, James B. Structure and function of enzymes of the Leloir pathway for galactose metabolism. J Biol Chem 2003;278:43885-8. https://doi.org/10.1074/jbc.R300025200
  3. Sohn YB. A diagnostic algorithm of newborn screening for galactosemia. J Korean Soc Inher Metab Dis 2015;15:101-9.
  4. Park IS, Cho HJ, Lee DH, Song JH. Galactosemia detected by neonatal screening test. J Korea Pediatr Soc 2003;46:440-6.
  5. Mauro M, Luigi C, Marina D and Giorgio F. Galactose activity and red blood cell Age. Age 1980;3:39-41. https://doi.org/10.1007/BF02432194
  6. Fang Y, Tamar A, Jason E, David B, Rhoads, Lynne L. Developmental regulation of galactokinase in suckling mouse liver by the Egr-1 transcription factor. IJPR 2004;55:822-9.
  7. Park HD, Bang YL, Park KU, Kim JK, Jeong BH, Kim YS, et al. Molecular and biochemical chacterization of the GALK1 gene in Korean patients with galactokinase deficiency. Mol Genet Metab 2007;91:234-8. https://doi.org/10.1016/j.ymgme.2007.04.005
  8. Federica S, Mauro M, Dwight S, Giuseppe N. Biochemical characterization of 2 GALK1 mutations in patients with galactokinase deficiency. Hum Mutat 2004;23:396.
  9. Park HD, Kim YK, Park KU, Kim JK, Song YH, Song JH. A Novel c.-22T>C mutation in GALK1 promoter is associated with elevated galactokinase phenotype. J Med Genet 2009 [cited 2016 November 1]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2667498.
  10. Hunter ML. Molecular investigations in the role of the GALK1 gene in galactokinase deficiency [Internet]. Joondalup, AU: Edith Cowan University; 2000 [cited 2016 November 1]. Available from: http://ro.ecu.edu.au/theses_hons/344.
  11. Charles T, Daniel E. Morse. Genetic regulation of galactokinase in Tetrahymena by cyclic AMP, glucose, and epinephrine. Proc Natl Acad Sci 1978;75:1810-4. https://doi.org/10.1073/pnas.75.4.1810
  12. Komrower GM. Long-term follow-up of galactosemia. Arch Dis Child 1970;45:367-73. https://doi.org/10.1136/adc.45.241.367