Prenatal and foetal autopsy findings in glutaric aciduria typeII

Background Glutaric aciduria type 2 is a rare, lethal disorder that affects metabolism of fatty acids caused by genetic defects in electron transfer (ETF) or in electron transfer flavoprotein dehydrogenase (ETFDH). We aimed to describe the pathological findings of 15 week old foetus, born from a consanguineous couple with 3 previous perinatal deaths. The last son died at 4 days of life and genetic analyses revealed a novel probably pathogenic variant atETFDH(c.706dupG + c.706dupG) that codifies for a truncated protein (p.Glu236Glyfs*5 + p.Glu236Glyfs*5). Case During the gestation, due to the medical familial history, prenatal echography and a chorial biopsy for ETFDH-associated glutaric aciduria analysis were carried out. Sanger sequencing confirmed the presence of the homozygous familial variant in theETFDHgene. The gestation was terminated and the foetal autopsy performed. Autopsy revealed prominent forehead, flat nasal bridge, malformed ears, intrauterine growth retardation, polycystic kidneys and steatosis in the liver, consistent with the diagnosis of glutaric aciduria type II. The comparison of present cases with the previously reported in the literature confirmed the presence of classical criteria, but also revealed the association with urogenital deformities, not previously stated. Conclusions Clinical and foetal findings allowed the characterisation of the novel variant (c.706dupG atETDFH) as pathogenic. Genotype-phenotype relationship is important when studying rare genetic disorders such as glutaric aciduria type II, as variants are usually family-specific, leading to a difficulty in the characterisation of their pathogenicity.