Leigh Syndrome After in Vitro Fertilization (IVF)

  • Dragos Albu UMF Carol Davila, Dionisie Lupu street no 37, Bucharest 20021, Romania
  • Alice Albu UMF Carol Davila, Dionisie Lupu street no 37, Bucharest 20021, Romania
  • Roxana Bohiltea UMF Carol Davila, Dionisie Lupu street no 37, Bucharest 20021, Romania
Keywords: in vitro fertilization, Leigh syndrome, mitochondrial DNA (deoxyribonucleic acid), PGD (preimplantation genetic diagnosis)

Abstract

Mitochondrial diseases are sporadic and very serious. The causes of these diseases are the mutations of the mitochondrial(mt) DNA (deoxyribonucleic acid) which is of maternal origin. The phenotypic variability of mitochondrial disease is determined by the simultaneous presence of normal and mutant mt DNA in the cytoplasm, a process called heteroplasmy. We present a case of Leigh syndrome in a twin pregnancy after in vitro fertilization (IVF). The two-month-old infant extracted by cesarean section at thirty-eight weeks of gestation was admitted to the hospital for worsening respiratory symptoms. The symptoms had started seven days before with fever and difficulty breathing; marked metabolic acidosis was discovered at the lumbar puncture that was done at admission in the hospital. We sent the patient to genetic testing due to congenital lactic acidosis. Leigh syndrome was strongly suspected. First, he had the sequencing analysis of the genes in Leigh syndrome and mitochondrial encephalopathy panel and a heterozygous variant of uncertain significance in the COQ8A gene, also known as ADCK3, c.521C>A p was found (Thr174Lys). Unfortunately, the infant died in the hospital due to cardiorespiratory arrest. The parents are now considering having another IVF procedure, and we are discussing all the possible variants with them.

References

Tachibana M, Kuno T, Yaegashi N. Mitochondrial replacement therapy and assisted reproductive technology: A paradigm shift toward treatment of genetic diseases in gametes or early embryos. Reprod Med Biol. 2018;17(4):421-433. Published 2018 Sep 19. doi:10.1002/rmb2.12230

Tajima H, Sueoka K, Moon SY, et al. The development of novel quantification assay for mitochondrial DNA heteroplasmy aimed at preimplantation genetic diagnosis of Leigh encephalopathy. J Assist Reprod Genet. 2007;24(6):227-232. doi:10.1007/s10815-007-9114-0

Bredenoord A, Dondorp W, Pennings G, de Die-Smulders C, Smeets B, de Wert G. Preimplantation genetic diagnosis for mitochondrial DNA disorders: ethical guidance for clinical practice. Eur J Hum Genet. 2009;17(12):1550-1559. doi:10.1038/ejhg.2009.88

Ng YS, Turnbull DM. Mitochondrial disease: genetics and management. J Neurol. 2016;263(1):179-191. doi:10.1007/s00415-015-7884-3

Harper JC, Aittomäki K, Borry P, et al. Recent developments in genetics and medically-assisted reproduction: from research to clinical applications. Hum Reprod Open. 2017;2017(3):hox015. Published 2017 Dec 4. doi:10.1093/hropen/hox015

Ishii T, Hibino Y. Mitochondrial manipulation in fertility clinics: Regulation and responsibility. Reprod Biomed Soc Online. 2018;5:93-109. Published 2018 Feb 28. doi:10.1016/j.rbms.2018.01.002

Dragos Albu, Alice Albu; The ratio of exogenous Luteinizing hormone to Follicle-stimulating hormone administered for controlled ovarian stimulation is associated with oocytes' number and competence. Biosci Rep 31 January 2020; 40 (1): BSR20190811. DOI: https://doi.org/10.1042/BSR20190811

Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod. 2011 Jun;26(6):1270-83. DOI: 10.1093/humrep/der037. Epub 2011 Apr 18. PMID: 21502182.

Jackson M, Marks L, May GHW, Wilson JB. The genetic basis of disease [published correction appears in Essays Biochem. 2020 Oct 8;64(4):681]. Essays Biochem. 2018;62(5):643-723. Published 2018 Dec 2. doi:10.1042/EBC20170053

Rai PK, Craven L, Hoogewijs K, Russell OM, Lightowlers RN. Advances in methods for reducing mitochondrial DNA disease by replacing or manipulating the mitochondrial genome. Essays Biochem. 2018;62(3):455-465. Published 2018 Jul 20. doi:10.1042/EBC20170113

Published
2021-11-23
Section
Articles