Clinical characteristics and somatic burden of patients with mucopolysaccharidosis II with or without neurological involvement: An analysis from the Hunter Outcome Survey

Heather Lau; Paul Harmatz; Jaco Botha; Jennifer Audi; Bianca Link

doi:10.1016/j.ymgmr.2023.101005

Clinical characteristics and somatic burden of patients with mucopolysaccharidosis II with or without neurological involvement: An analysis from the Hunter Outcome Survey

Mol Genet Metab Rep. 2023 Sep 8:37:101005. doi: 10.1016/j.ymgmr.2023.101005. eCollection 2023 Dec.

Authors

Heather Lau¹, Paul Harmatz², Jaco Botha³, Jennifer Audi³, Bianca Link⁴

Affiliations

¹ Yale School of Medicine, New Haven, CT, USA.
² UCSF Benioff Children's Hospital Oakland, Oakland, CA, USA.
³ Takeda Pharmaceuticals International AG, Zurich, Switzerland.
⁴ Division of Metabolism, Connective Tissue Unit, University Children's Hospital Zurich, Zurich, Switzerland.

Abstract

Approximately two-thirds of patients with mucopolysaccharidosis II (MPS II; Hunter syndrome) have neuronopathic disease, with central nervous system involvement; one-third have non-neuronopathic disease. This analysis of data from the Hunter Outcome Survey (HOS) compared the clinical manifestations and surgical and nonsurgical procedure history in patients with neuronopathic or non-neuronopathic MPS II. Prospective patients were identified in July 2018 in HOS for inclusion in this analysis as those with stable cognitive impairment status as assessed at 10 years of age and at a minimum of one follow-up visit at 11 to <20 years of age. Patients were stratified according to cognitive impairment status at 10 years into neuronopathic and non-neuronopathic groups, and clinical manifestations and surgical and nonsurgical procedure history were compared between the two groups. In total, 193 patients had cognitive impairment status assessments available (at 10 years and 11 to <20 years of age), 151 of whom had stable cognitive impairment status and were included; 100/151 (66.2%) were in the neuronopathic group and 51/151 (33.8%) in the non-neuronopathic group. The proportion of patients demonstrating manifestations by system organ class and the number of surgical and nonsurgical procedures per patient were broadly comparable in the neuronopathic and non-neuronopathic groups both before and after patients' 10th birthdays. The most common manifestations before patients' 10th birthdays, including facial features, joint stiffness and limited function, and hepatomegaly were reported in >80% of patients in both groups. For the neuronopathic and non-neuronopathic groups, the median [10th percentile, 90th percentile] number of different types of surgical and nonsurgical procedures per patient (3 [1, 6] and 3 [1, 7], respectively) and of all procedures per patient (4 [1, 10] and 5 [2, 11], respectively) before patients' 10th birthdays were similar, although the type of procedure may have differed. Thus, in the first two decades of life, patients with non-neuronopathic disease were found to have similar somatic manifestations to those of the neuronopathic group and undergo procedures for complications as often as those with neuronopathic disease.

Keywords: Enzyme replacement therapy; Hunter Outcome Survey; Mucopolysaccharidosis type II; Neuronopathic phenotype; Non-neuronopathic phenotype; Surgery.