Novel Biallelic Variants in CPOX Gene in a Case of Hereditary Coproporphyria With Antenatal Onset and Adverse Neonatal Outcome: A Potential Diagnostic Clue of Harderoporphyria?

Harderoporphyria (MIM #618892), one of the rarest disorders involving heme biosynthesis, is caused by variants in the coproporphyrinogen III oxidase (CPOX) gene. This article examines the case of a woman who experienced two previous unexplained neonatal deaths and subsequently presented for prenatal care. Follow-up scans showed signs of severe fetal anemia at 35 weeks, which led to an emergency C-section; despite these efforts, the baby died on day 3. Exome sequencing analysis detected two novel biallelic variants in CPOX gene, also identified in one of the other deceased siblings. This finding raises the hypothesis that this phenotype segregates in the presence of these two variants, leading to the development of an early onset and severe form of antenatal anemia. Prenatal ultrasounds and exome sequencing are key in obtaining an early diagnosis of this rare monogenic disease.