Propionic acidemia identified in twin siblings conceived by in vitro fertilization (IVF) with parents who were unknown carriers of a PCCA mutation

BMC Pregnancy and Childbirth

Wujuan Shi¹  Guojie Wang²  Xiaohong Bai²  Ye Tian² 

[1] Department of Neonatology, Tianjin Children’s Hospital, No.238, Longyan Road, Beichen District, 300134, Tianjin, China;Reproductive Medicine Center, Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, No.154, Anshan Road, Heping district, 300052, Tianjin, China;

关键词: Propionic acidemia;    PCCA;    In vitro fertilization;    Genetic carrier screening;   

DOI  :  10.1186/s12884-020-03391-z

来源: Springer

【 摘 要 】

BackgroundPropionic acidemia (PA) is a severe monogenic disorder characterized by a deficiency of the mitochondrial protein propionyl-CoA carboxylase (PCC) enzyme, which is caused by mutations in the PCCA or PCCB gene. Preconception carrier screening could provide couples with meaningful information for their reproductive options; however, it is not widely performed in China.Case presentationThis report describes a case of dizygotic twin siblings conceived by in vitro fertilization (IVF) and diagnosed with propionic acidemia (PA). Their parents had no history of PA. Tandem mass spectrometry and urine gas chromatography/mass spectrometry (GC/MS) of the twin siblings revealed markedly elevated propionyl carnitine (C3), C3/C2, and 3-hydroxypropionate in the plasma and urine. Whole-exome sequencing was performed for the twin siblings. A homozygous missense mutation, c.2002G > A (p.Gly668Arg) in PCCA, was identified in the twin siblings. Sanger sequencing confirmed the homozygous mutation in the twin siblings and identified their parents as heterozygous carriers of the c.2002G > A mutation in PCCA. Both neonates in this case died. This is an emotionally and financially devastating outcome that could have been avoided with genetic carrier screening before conception. If couples are screened before IVF and found to be silent carriers, then reproductive options (such as preimplantation genetic diagnosis or prenatal diagnosis) can be offered to achieve a healthy newborn.ConclusionThis case is a reminder to infertile couples seeking IVF that it is beneficial to clarify whether they are silent carriers before undergoing IVF.

【 授权许可】

CC BY