Mucopolysaccharidosis (MPS) type II (Hunter syndrome) is a rare X-linked, recessive, lysosomal storage disorder caused by the deficit of the enzyme iduronate 2-sulfatase (IDS), resulting in accumulation of glycosaminoglycans (GAGs) impairing cellular function in multiple organ systems. Idursulfase (Elaprase, Takeda Pharmaceuticals) and idursulfase beta (Hunterase, GC Biopharma Corp.) are the two currently available enzyme replacement therapies (ERT) for MPS II in Malaysia. ERT in patients with MPS II is associated with improvements in somatic symptoms, pulmonary function, endurance, joint mobility, and quality of life. Though mostly well tolerated, infusion-associated reactions (IARs), such as allergic (IgE-mediated) or nonallergic (non- immunologic) reactions can develop during ERT. In certain cases, when patients develop recurrent IARs despite reduced infusion rate and premedication, either interruption or cessation of ERT might be necessary. However, interruption of ERT is associated with worsening of clinical symptoms such as recurrent respiratory infections, difficulty in standing and walking, and increased joint stiffness, emphasizing the need for continuation of ERT. Here we report successful long-term experience with the use of idursulfase beta in two adolescent Malaysian patients with MPS II, who experienced recurrent infusion-associated reactions warranting discontinuation of ERT with idursulfase.
Approximately one-half of the phenotypic susceptibility to atherosclerotic cardiovascular disease (ASCVD) has a genetic basis. Although individual allelic variants generally impart a small effect on risk for ASCVD, an emerging body of data has shown that the aggregation and weighting of many of these genetic variations into "scores" can further discriminate an individual's risk beyond traditional risk factors alone. Consistent with the theory of population genetics, such polygenic risk scores (PRS) appear to be ethnicity specific because their elements comprise single-nucleotide variants that are always ethnicity specific. The currently available PRS are derived predominantly from European ancestry and thus predictably perform less well among non-European participants, a fact that has implications for their use in the Asia-Pacific region. This paper describes the current state of knowledge of PRS, the available data that support their use in this region, and highlights the needs moving forward to safely and effectively implement them in clinical care in the Asia-Pacific region.