Elevation of glycosaminoglycans in the amniotic fluid of a fetus with mucopolysaccharidosis VII†. (12th March 2017) - Kubaski, Francyne
Abstract: Objective: The aim of this study was to quantify glycosaminoglycans (GAGs) in amniotic fluid (AF) from an MPS VII fetus compared with age‐matched fetuses obtained from normal pregnancies. Method: Disaccharides were measured by liquid chromatography tandem mass spectrometry, compared to age‐matched controls. Enzyme assay was performed in AF supernatant or cultured amniocytes. GUSB was analyzed by next generation sequencing using Ion Torrent Personal Genome Machine with a customized panel. Results: No activity of β‐glucuronidase was detected in fetal cells. The pregnancy was spontaneously terminated in the third trimester. Genetic studies identified a homozygous mutation of p.N379D (c.1135A > G) in the GUSB gene. Liquid chromatography tandem mass spectrometry showed that chondroitin sulfate, dermatan sulfate, heparan sulfate, and keratan sulfate levels were markedly increased in the MPS VII AF, compared to those in age‐matched control AF (dermatan sulfate, heparan sulfate, and chondroitin‐6‐sulfate more than 10 × than age‐matched controls; chondroitin‐4‐sulfate and keratan sulfate more than 3 times higher). Conclusion: This is the first report of specific GAG analysis in AF from an MPS VII fetus, indicating that GAG elevation in AF occurs by 21 weeks of gestation and could be an additional tool for prenatal diagnosis of MPS VII and potentially other MPS types. © 2017 John Wiley & Sons, Ltd. Abstract : What's already known about this topic? Mucopolysaccharidosis VII (MPS VII; Sly Syndrome) is an autosomal recessive disorder caused by deficiency of β‐glucuronidase, leading to accumulation of primary glycosaminoglycans (GAGs); MPS VII has a broad clinical spectrum from the most severe lethal hydrops fetalis to attenuated forms with survival into adulthood despite somatic and cognitive impairment; GAGs are elevated in a fetus with MPS VII. What does this study add? Not only primary GAGs (HS, DS) but KS are accumulated as early as 21 weeks of gestation; This is the first report of p.N379D substitution in GUSB; Quantification of GAGs by mass spectrometry applies to prenatal diagnosis, prognosis, and screening for MPS.