The youngest pair of siblings with Mucopolysaccharidosis type IVA to receive enzyme replacement therapy to date: A case report

Mucopolysaccharidosis type IVA (OMIM 253000) is an autosomal recessive disorder caused by defective activity of the N-acetylgalactosamine 6-sulfatase (GALNS) enzyme. In 2014, enzyme replacement therapy (ERT) using recombinant human GALNS became available for affected patients. There is a limited number of studies to date that have explored the effect of ERT in infancy and there is also a lack of data assessing the effect of ERT in systems other than the skeletal. Here, we report on the effect of ERT in the youngest pair of siblings treated to date: Patient A, currently 4 years old, who started treatment at the age of 5 months; and Patient B, currently 3 years old, who started treatment at 58 days of life. Moreover, we investigate the effect of early ERT on the cardiovascular system. Our results show that, even when ERT is started before 2 months of age, it cannot fully prevent disease progression. As for the effect of ERT on the cardiovascular system, our preliminary results suggest that early treatment might play a role in preserving a normal left ventricular mass index in affected patients at least up to 1 year, but further observation over time will be required. Overall, this report shows that early diagnosis remains crucial and that prompt initiation of ERT has limited effect in slowing progression of the skeletal phenotype, thus confirming the need for new therapeutic approaches that target the skeletal system in affected patients.