Early enzyme replacement therapy enables a successful hematopoietic stem cell transplantation in mucopolysaccharidosis type IH: Divergent clinical outcomes in two Japanese siblings.

Mucopolysaccharidosis type IH (MPS IH, Hurler syndrome) is a progressive, multisystem autosomal recessive lysosomal storage disorder resulting in the consequent accumulation of glycosaminoglycans. It is well recognized that early hematopoietic stem cell transplantation (HSCT) prevents neurocognitive decline in MPS IH. We followed the divergent clinical course in two Japanese siblings with MPS IH. The elder sister (proband) received a diagnosis of MPS IH at 6 months old. At the time of this diagnosis enzyme replacement therapy (ERT) was not available in Japan. She developed severe and recurrent respiratory disease and died at 1 year 10 months of age. Her younger sister also received a diagnosis of MPS IH, but at 18 days of age, and started ERT at 34 days of age. ERT continued until 8 months of age and prevented the progression of somatic manifestations of MPS IH. She received HSCT at 9 months old. Five years after HSCT she had no symptoms of MPS IH except for mild signs of dysostosis multiplex and mild cardiac valvular disease. Her neurological function was generally preserved compared with her elder sister. The prognosis and quality of life differed significantly between the sisters. Therefore, early HSCT can preserve neurocognition by preventing the neurodegeneration from MPS IH. In addition, ERT initiated during the asymptomatic period prevented the patient from developing somatic manifestations and enabled successful HSCT in this case.

Tuning microchannel wettability and fabrication of multiple-step Laplace valves.

By using characteristics of titania nanoparticles, a patterning and tuning method of microchannel surface wettability was developed for microfluid control. Titania modification of a microchannel provided a nanometer-sized surface roughness and the subsequent hydrophobic treatment made the surface superhydrophobic. Photocatalytic decomposition of the coated hydrophobic molecules was used to pattern the surface wettability which was tuned in the range from superhydrophobic to superhydrophilic under controlled photoirradiation. Four-step wettability-based Laplace valves working as passive stop valves (6.8-12.5 kPa pressure barrier) were prepared by using the patterned and tuned surface. As a demonstration, a batch operation system consisting of two sub-nL dispensers and a reaction chamber was constructed. Fundamental liquid manipulations required for the batch operation were successfully conducted, including liquid measurement (390 and 770 pL), transportation, injection into the chamber, and retention in the chamber. To verify the quantitative operation, the system was applied to a fluorescence quenching experiment as an example of volumetric analyses. The present method provides flexible patterning in a wide range of tuned wettability surfaces in microchannels even after channel fabrication and it can be applied to various two- or multi-phase microfluidic systems.