Preview

Pediatric pharmacology

Advanced search

Premature ovarian insufficiency in patients with galactosemia

https://doi.org/10.15690/pf.v21i2.2721

Abstract

Background. Galactosemia is a congenital disorder of carbohydrate metabolism caused by a defect in any of the enzymes of galactose metabolism. One of the long-term complications is premature ovarian insufficiency (POI), which is more common in patients with the c.563A>G (Q188R) mutation in the homozygous state in the galactose-1-phosphate uridylyltransferase (GALT) gene. At the same time, fertility factors may be higher in patients with POI caused by classical galactosemia (CG) compared with other causes of POI, which makes it difficult to resolve the issue of the need to use fertility preservation methods for this group of patients in the prepubescent period. Case report. This article describes two clinical observations of patients with CG who were diagnosed with hypergonadotropic hypogonadism. Patient A. was initiated hormone replacement therapy (HRT) at the age of 11, and according to the results of osteodensitometry, there is currently no decrease in bone mineral density. In patient C. at the age of 14, before the start of HRT, ovaries without pronounced follicular apparatus, osteopenia and osteoporosis were detected. The issue of the necessity and timing of the use of fertility preservation methods is being considered. Conclusion. Patients with CG are recommended to monitor hormonal profile indicators for timely administration of HRT. Cryopreservation of ovarian tissue should be considered as one of the options for maintaining fertility in patients with CG, taking into account that some of them still have the possibility of spontaneous pregnancy, despite the POI.

About the Authors

Irina V. Karachentsova
N.I. Pirogov Russian National Research Medical University
Russian Federation

MD, PhD

1, Ostrovityanova Str., building 7, Moscow, 117997


Disclosure of interest:

Not declared.



Elena V. Sibirskaya
N.I. Pirogov Russian National Research Medical University; Center for Adolescent Reproductive Health protection in the Moscow Region; Russian Children’s Clinical Hospital of N.I. Pirogov Russian National Research Medical University; A.I. Evdokimov Moscow State University of Medicine and Dentistry
Russian Federation

MD, PhD, Professor

Moscow


Disclosure of interest:

Not declared.



Adelina A. Khairullina
N.I. Pirogov Russian National Research Medical University
Russian Federation

MD

Moscow


Disclosure of interest:

Not declared.



References

1. Haskovic M, Coelho AI, Bierau J, et al. Pathophysiology and targets for treatment in hereditary galactosemia: A systematic review of animal and cellular models. J Inherit Metab Dis. 2020;43(3):392– 408. doi: https://doi.org/10.1002/jimd.12202

2. Flechtner I, Viaud M, Kariyawasam D, et al. Puberty and fertility in classic galactosemia. Endocr Connect. 2021;10(2):240–247. doi: https://doi.org/10.1530/EC-21-0013

3. Colhoun HO, Rubio Gozalbo EM, Bosch AM, et al. Fertility in classical galactosaemia, a study of N-glycan, hormonal and inflammatory gene interactions. Orphanet J Rare Dis. 2018;13(1):164. doi: https://doi.org/10.1186/s13023-018-0906-3

4. Jumbo-Lucioni PP, Garber K, Kiel J, et al. Diversity of approaches to classic galactosemia around the world: a comparison of diagnosis, intervention, and outcomes. J Inherit Metab Dis. 2012;35(6):1037– 1049. doi: https://doi.org/10.1007/s10545-012-9477-y

5. Kumar S U, Kumar D T, R S, Doss C GP, Zayed H. An extensive computational approach to analyze and characterize the functional mutations in the galactose-1-phosphate uridyl transferase (GALT) protein responsible for classical galactosemia. Comput Biol Med. 2020;117:103583. doi: https://doi.org/10.1016/j.compbiomed.2019.103583

6. Hagen-Lillevik S, Rushing JS, Appiah L, et al. Pathophysiology and management of classic galactosemic primary ovarian insufficiency. Reprod Fertil. 2021;2(3):R67–R84. doi: https://doi.org/10.1530/RAF-21-0014

7. European Society for Human Reproduction and Embryology (ESHRE) Guideline Group on POI; Webber L, Davies M, Anderson R, et al. ESHRE Guideline: management of women with premature ovarian insufficiency. Hum Reprod. 2016;31(5):926–937. doi: https://doi.org/10.1093/humrep/dew027

8. Derks B, Rivera-Cruz G, Hagen-Lillevik S, et al. The hypergonadotropic hypogonadism conundrum of classic galactosemia. Hum Reprod Update. 2023;29(2):246–258. doi: https://doi.org/10.1093/humupd/dmac041

9. Hagen-Lillevik S, Johnson J, Lai K. Early postnatal alterations in follicular stress response and survival in a mouse model of Classic Galactosemia. J Ovarian Res. 2022;15(1):122. doi: https://doi.org/10.1186/s13048-022-01049-2

10. van Kasteren YM, Schoemaker J. Premature ovarian failure: a systematic review on therapeutic interventions to restore ovarian function and achieve pregnancy. Hum Reprod Update. 1999;5(5):483– 492. doi: https://doi.org/10.1093/humupd/5.5.483

11. van Erven B, Berry GT, Cassiman D, et al. Fertility in adult women with classic galactosemia and primary ovarian insufficiency. Fertil Steril. 2017;108(1):168–174. doi: https://doi.org/10.1016/j.fertnstert.2017.05.013

12. Welling L, Bernstein LE, Berry GT, et al. International clinical guideline for the management of classical galactosemia: diagnosis, treatment, and follow-up. J Inherit Metab Dis. 2017;40(2):171–176. doi: https://doi.org/10.1007/s10545-016-9990-5

13. Sanders RD, Spencer JB, Epstein MP, et al. Biomarkers of ovarian function in girls and women with classic galactosemia. Fertil Steril. 2009;92(1):344–351. doi: https://doi.org/10.1016/j.fertnstert.2008.04.060

14. Gubbels CS, Kuppens SM, Bakker JA, et al. Pregnancy in classic galactosemia despite undetectable anti-Müllerian hormone. Fertil Steril. 2009;91(4):1293.e13–e16. doi: https://doi.org/10.1016/j.fertnstert.2008.12.031

15. Mamsen LS, Kelsey TW, Ernst E, et al. Cryopreservation of ovarian tissue may be considered in young girls with galactosemia. J Assist Reprod Genet. 2018;35(7):1209–1217. doi: https://doi.org/10.1007/s10815-018-1209-2

16. Haskovic M, Poot WJ, van Golde RJT, et al. Intrafamilial oocyte donation in classic galactosemia: ethical and societal aspects. J Inherit Metab Dis. 2018;41(5):791–797. doi: https://doi.org/10.1007/s10545-018-0179-y

17. Hu X, Zhang YQ, Lee OW, et al. Discovery of novel inhibitors of human galactokinase by virtual screening. J Comput Aided Mol Des. 2019;33(4):405–417. doi: https://doi.org/10.1007/s10822-019-00190-3

18. Balakrishnan B, An D, Nguyen V, et al. Novel mRNA-Based Therapy Reduces Toxic Galactose Metabolites and Overcomes Galactose Sensitivity in a Mouse Model of Classic Galactosemia. Mol Ther. 2020;28(1):304–312. doi: https://doi.org/10.1016/j.ymthe.2019.09.018

19. Balakrishnan B, Siddiqi A, Mella J, et al. Salubrinal enhances eIF2α phosphorylation and improves fertility in a mouse model of Classic Galactosemia. Biochim Biophys Acta Mol Basis Dis. 2019;1865(11):165516. doi: https://doi.org/10.1016/j.bbadis.2019.07.010


Review

For citations:


Karachentsova I.V., Sibirskaya E.V., Khairullina A.A. Premature ovarian insufficiency in patients with galactosemia. Pediatric pharmacology. 2024;21(2):119-125. (In Russ.) https://doi.org/10.15690/pf.v21i2.2721

Views: 330


ISSN 1727-5776 (Print)
ISSN 2500-3089 (Online)