Case report of neuronopathic mucopolysaccharidosis type II: Early intracerebroventricular enzyme replacement therapy and hematopoietic cell transplantation with developmental outcomes up to 5 years of age

Neuronopathic mucopolysaccharidosis type II (MPS II) is a severe lysosomal storage disorder associated with early-onset developmental regression and a poor prognosis. Although enzyme replacement therapy (ERT) and hematopoietic cell transplantation (HCT) have been employed to address systemic symptoms, they have not demonstrated sufficient efficacy in treating central nervous system (CNS) involvement. The intracerebroventricular administration of idursulfase beta has emerged as a novel approach for targeting CNS manifestations. Here, we report the clinical course of a male patient diagnosed with neuronopathic MPS II at 2 months of age, based on family history and genetic analysis. Intravenous ERT was initiated early, followed by the introduction of intracerebroventricular idursulfase beta at 10 months, and HCT at 23 months. Since then, only intracerebroventricular ERT has been continued. At 5 years of age, the patient exhibited age-appropriate neurodevelopment, stable cognitive function, and normal physical growth without signs of developmental regression. Imaging findings remained stable, and cerebrospinal fluid biomarkers normalized. Notably, the patient harbored a missense variant potentially associated with residual enzymatic activity, which may have contributed to favorable outcomes. To our knowledge, this is the first reported case in which normal development was maintained until 5 years of age in a patient with neuronopathic MPS II. This case highlights the potential benefits of early diagnosis and a multimodal therapeutic strategy, including intracerebroventricular ERT and HCT, for preserving neurodevelopment. It also holds significance as a rare but valuable example, suggesting the efficacy of a novel treatment paradigm for a condition traditionally associated with a poor prognosis.