Impact of the Timing of Enzyme Replacement Therapy Initiation and Cognitive Impairment Status on Outcomes for Patients with Mucopolysaccharidosis II (MPS II) in the United States: A Retrospective Chart Review.

Background: Mucopolysaccharidosis II (MPS II; Hunter syndrome; OMIM 309900) is a rare, X-linked, lysosomal storage disease caused by deficient iduronate-2-sulfatase activity. Accumulation of glycosaminoglycans results in multisystemic disease manifestations, which may include central nervous system involvement and cognitive impairment (CI). Patients with MPS II experience a high disease burden, leading to extensive healthcare resource utilization (HRU) and reduced quality of life. Objectives: This study aimed to assess the impact of timing of enzyme replacement therapy (ERT) initiation and CI status on the clinical characteristics and HRU of patients with MPS II. Methods: A retrospective medical chart review of 140 male patients who received a diagnosis of MPS II between 1997 and 2017 was performed at 19 US sites; data on disease manifestations and HRU stratified by age at ERT initiation or CI status were analyzed for the full study population and a subgroup of patients who received a diagnosis of MPS II before the age of 6 years. Results: In patients initiating ERT before 3 years of age, there was a trend toward lower symptom burden and HRU compared with patients who initiated ERT at an older age. Evaluation of developmental and behavioral signs and symptoms in the full study population showed that communication delay (70.0% of patients), cognitive delay (62.1%), behavioral problems (52.9%), and toileting delay (50.0%) were particularly common; earliest documented signs and symptoms were motor delay (median [range] age at first documentation: 4.2 [0.9-18.7] years) and behavioral problems (4.4 [0.6-13.7] years). Patients with CI generally experienced greater symptom burden and higher HRU than those without CI, with the most notable differences documented for communication and toileting delays. Formal cognitive testing was documented in <30% of cognitively impaired patients diagnosed with MPS II before the age of 6 years. Conclusions: Our findings reinforce previous recommendations for ERT to be initiated early to maximally benefit patients with MPS II, especially those younger than 3 years old. Cognitively impaired patients experience a particularly high disease burden and HRU. Patient care could be improved with early cognitive assessments and the development of treatments that address cognitive decline.