Combined Treatment of Intracerebroventricular Enzyme Replacement and Cord Blood Transplantation in Patients with Mucopolysaccharidosis Type II Diagnosed by Newborn Screening

Enzyme replacement therapy (ERT) for central nervous system symptoms and newborn screening (NBS) are available in Japan for patients with mucopolysaccharidosis type II (MPS II). The participants were individuals referred to our facility through NBS who were suspected of having neuronopathic MPS II. We reviewed the clinical course of patients who received intracerebroventricular (ICV)-ERT, idursulfase beta (Hunterase®), followed by hematopoietic stem cell transplantation (HSCT) using umbilical cord blood. Longitudinal measurements of heparan sulfate (HS) in the cerebrospinal fluid (CSF) were performed as a therapeutic biomarker, and developmental age was evaluated. Three patients diagnosed and treated with ICV-ERT received cord blood transplantation (CBT). All patients achieved successful engraftment with no severe complications except for one patient with sinusoidal obstruction syndrome. The HS in the CSF showed a temporary increase during the ERT discontinuation period owing to CBT and a subsequent reduction after the resumption of ICV-ERT. The patients exhibited age-appropriate development. The pattern of change in HS suggests the importance of continuing ICV-ERT even after HSCT. The combination of ICV-ERT and CBT may yield promising outcomes in patients with neuronopathic MPS II and underscores the importance of early intervention through NBS.