ALG8-CDG: advances in molecular and prenatal phenotyping facilitate prenatal diagnosis and genetic counseling.

This article focuses on the first prenatal diagnosis and comprehensive characterization of ALG8-congenital disorder of glycosylation (ALG8-CDG), a rare autosomal recessive metabolic disorder caused by pathogenic variants in the ALG8 gene. The study describes two fetuses from a single family presenting with severe multisystem prenatal abnormalities including fetal hydrops, skeletal anomalies, cardiac defects, cataracts, renal and gastrointestinal abnormalities, and intrauterine growth restriction, confirmed by ultrasound, umbilical cord blood biochemistry, autopsy, and placental pathology. Genetic testing identified a novel compound heterozygous mutation in ALG8, comprising a missense variant (c.754T>C, p.Ser252Pro) and a partial deletion of exons 1–2. These findings expand the prenatal phenotypic spectrum of ALG8-CDG and highlight the importance of integrated prenatal imaging, biochemical, pathological, and genetic assessments for diagnosis, counseling, and potential intervention in affected pregnancies.