Mucopolysaccharidoses type VII (Sly syndrome): New uncertain pathogenic variants in GUSB gene

Mucopolysaccharidoses (MPS) are a group of diseases caused by the accumulation of glycosaminoglycans (GAGs). Currently, eleven enzyme deficiencies have been described, with eight different MPS subtypes reported. MPS VII, also known as Sly syndrome, is a recessive disorder caused by pathogenic variants in the GUSB gene. This results in dysfunction of the enzyme β-glucuronidase, which can lead to non-immune hydrops fetalis (NIHF). The patient was a 22-week foetus with pathological nuchal translucency and unfavourable prognosis based on radiological criteria; as a result, both parents opted to terminate the pregnancy. Post mortem examination revealed several hallmarks of NIHF. Moreover, microscopic examination showed widespread histiocytes with microvacuolated cytoplasm. Genetic testing demonstrated biallelic variants in exon 8 of the GUSB gene, but both of uncertain meaning. Subsequent histological findings suggested that these GUSB gene variants resulted in MPS VII.