Diagnosis and Emerging Treatment Strategies for Mucopolysaccharidosis VII (Sly Syndrome)

Abstract

Mucopolysaccharidosis VII (MPS VII, Sly syndrome) is an ultra-rare lysosomal disease caused by a deficiency of the enzyme β-glucuronidase (GUS). The diagnosis is suspected based on a range of symptoms that are common to many other MPS types, and it is confirmed through biochemical and molecular studies. Besides supportive treatment, current and emerging treatments include enzyme replacement therapy, hematopoietic stem cell transplantation, and gene therapy. This review summarizes the clinical manifestations, diagnosis, and emerging treatments for MPS VII.

Keywords: Sly syndrome; enzyme replacement therapy; gene therapy; hematopoietic stem cell transplantation; lysosomal disorders; mucopolysaccharidosis type VII.

Figure 1

Clinical manifestations of MPS VII. Clinical photographs show coarse facial features, with a short neck and abnormal dentition (A), as well as joint contractures with claw hands (B), and genu valgum (C). Radiographic signs of dysostosis multiplex include broad ribs, hip dysplasia and scoliosis (D); thoracolumbar gibbus (E); odontoid dysplasia (F). Informed consent was obtained for the publication of patient images.

Figure 2

Therapeutic approaches for MPS VII. Enzyme replacement therapy leads to significant improvement in patient’s quality of life, with disease correction in many visceral tissues; however, it is costly, requires the support of health centers, and there is the possibility of immune reactions. Hematopoietic stem cell transplantation, on the other hand, is effective in the brain, though it must be performed early in life, it takes time for cells to fully engraft and be effective, a matching donor is necessary, and there is always a life-threatening risk of graft rejection or graft-versus-host disease. Finally, gene therapy should be a once-in-a-lifetime treatment (or a few times throughout the lifespan of the patient), able to target the central nervous system specifically and improve cognition significantly, although it can be a very invasive procedure with associated risks inherent to viral vectors.