Box 1.

Brief description of mucopolysaccharidoses

Mucopolysaccharidoses (MPS) are a group of seven heritable conditions that have an autosomal recessive inheritance pattern, except for MPS II which is X-linked [43]. Overall birth prevalence estimates for MPS vary by country/region and range from 1.04 to 4.8 per 100,000 live births [44]. These disorders are characterized by specific enzyme deficiencies that cause an accumulation of glycosaminoglycans (GAG) in the lysosomes of most cells [43, 45]. This buildup of GAG results in a wide spectrum of cell, tissue, and organ damage. The clinical manifestations of MPS begin early in life and are chronic, progressive, and typically involve multiple organ systems. Common clinical symptoms include: vision, hearing, cardiovascular, airway, and joint problems, organomegaly, musculoskeletal and facial abnormalities, among others [43, 45]. Similar to many other rare diseases, there is substantial clinical heterogeneity both between different MPS and within the same MPS [43, 45]. The spectrum ranges from mildly affected to severely affected. In addition to other symptoms, severely affected individuals may also experience neurocognitive deficits that are not present in more attenuated forms of the diseases [43, 45]. Currently, transformative treatments are limited for MPS, so care is generally supportive to help manage various symptoms [45]. For those with severe MPS I, early hematopoietic stem cell transplantation is recommended as standard of care to slow the progression of symptoms, particularly neurocognitive impairments [46, 47]. In addition, enzyme replacement therapy, an expensive orphan drug, is available for MPS I, II, and VI32,33; however, the extent of its efficacy is debated in the literature.