First Report of a Patient with MPS Type VII, Due to Novel Mutations in <i>GUSB</i>, Who Underwent Enzyme Replacement and Then Hematopoietic Stem Cell Transplantation

• Main Authors: Patricia Dubot, Frédérique Sabourdy, Geneviève Plat, Charlotte Jubert, Claude Cancès, Pierre Broué, Guy Touati, Thierry Levade
• Format: Article
• Language: English
• Published: MDPI AG 2019-10-01
• Series: International Journal of Molecular Sciences
• Subjects: mucopolysaccharidosis; enzyme replacement therapy; transplantation; glycosaminoglycan; glucuronidase; sly syndrome
• Online Access: https://www.mdpi.com/1422-0067/20/21/5345

We report the case of a boy who was diagnosed with mucopolysaccharidosis (MPS) VII at two weeks of age. He harbored three missense &#946;-glucuronidase (<i>GUSB)</i> variations in exon 3: two novel, c.422A&gt;C and c.424C&gt;T, inherited from his mother, and the rather common c.526C&gt;T, inherited from his father. Expression of these variations in transfected HEK293T cells demonstrated that the double mutation c.422A&gt;C;424C&gt;T reduces &#946;-glucuronidase enzyme activity. Enzyme replacement therapy (ERT), using UX003 (vestronidase alfa), was started at four months of age, followed by a hematopoietic stem cell allograft transplantation (HSCT) at 13 months of age. ERT was well tolerated and attenuated visceromegaly and skin infiltration. After a severe skin and gut graft-versus-host disease, ERT was stopped six months after HSCT. The last follow-up examination (at the age of four years) revealed a normal psychomotor development, stabilized growth curve, no hepatosplenomegaly, and no other organ involvement. Intriguingly, enzyme activity had normalized in leukocytes but remained low in plasma. This case report illustrates: (i) The need for an early diagnosis of MPS, and (ii) the possible benefit of a very early enzymatic and/or cellular therapy in this rare form of lysosomal storage disease.