Female Patients With Mucopolysaccharidosis II (MPS II): Insights From the Hunter Outcome Survey.

Mucopolysaccharidosis II is a rare, X-linked disease, with very few reports of affected female patients. Natural history data describe a predominantly male population, and appropriate disease characterization in female patients is lacking. This analysis explores the somatic disease burden and clinical progression of female patients with MPS II enrolled in the Hunter Outcome Survey (HOS; NCT03292887), a global disease registry. In total, 15 female patients were identified, representing 1.1% of the total patients in HOS. The median ages at first symptom onset and diagnosis were 1.8 and 3.1 years, respectively. A total of 8/14 (57.1%) of patients had cognitive impairment at the latest visit. X-chromosome abnormalities were reported in two patients. Most patients (11/15, 73.3%) had received at least one dose of idursulfase, which was generally well tolerated; no serious adverse events during follow-up were considered treatment-related. Musculoskeletal and ear symptoms were present in all 14 patients with data recorded. Almost all females also experienced neurological, abdominal/gastrointestinal, and pulmonary disease, similar to the symptomatology reported in males. Most patients underwent surgery (41 procedures in 12 patients). Two participants had a male sibling with MPS II who was also enrolled in HOS. Both sibling sets had missense variants and demonstrated several differences in signs/symptoms between the male and female siblings. Notably, only the female siblings displayed cognitive impairment. This report illustrates the disease burden in female patients with MPS II, helping to inform clinicians about the likely prognosis for this extremely rare subgroup of patients.