Outcomes after Hematopoietic Stem Cell Transplantation for Children with I-Cell Disease

Mucolipidosis type II (MLII), or I-cell disease, is a rare but severe disorder affecting localization of enzymes to the lysosome, generally resulting in death before the 10th birthday. Although hematopoietic stem cell transplantation (HSCT) has been used to successfully treat some lysosomal storage diseases, only 2 cases have been reported on the use of HSCT to treat MLII. For the first time, we describe the combined international experience in the use of HSCT for MLII in 22 patients. Although 95% of the patients engrafted, overall survival was low, with only 6 patients (27%) alive at last follow-up. The most common cause of death post-transplant was cardiovascular complications, most likely due to disease progression. Survivors were globally delayed in development and often required complex medical support, such as gastrostomy tubes for nutrition and tracheostomy with mechanical ventilation. Although HSCT has demonstrated efficacy in treating some lysosomal storage disorders, the neurologic outcome and survival for patents with MLII were poor. Therefore, new medical and cellular therapies should be sought for these patients

Caldera size modulated by the yield stress within a crystal-rich magma reservoir

The largest volcanic eruptions in the geologic record have no analogue in the historical record. These eruptions had global impacts1,2, but are known only through their eruptive products. They have left behind calderas that formed as the surface collapsed when eruption evacuated magma chambers at 5–15 km depths3,4. It is generally assumed that calderas reflect the spatial dimensions of underlying magma reservoirs. Here we use a numerical model of conduit flow and dynamic magma-chamber drainage to show that caldera size can be affected by the material properties of crystal-rich silicic magma. We find that magma in the chamber can experience a rheological transition during eruption. This transition causes magma near the conduit to behave as a fluid, whereas magma farther away behaves elastically and remains locked. The intervening surface—the yield surface—expands through the chamber as eruption progresses. If a yielding transition occurs, calderas can form before complete mobilization of the entire reservoir. The resulting distribution of eruption volumes is then bimodal, as observed in the geologic record. We suggest that the presence or absence of a magma yield stress determines whether caldera size reflects the true spatial extent of magma storage