Summary:Hurler syndrome (MPS-IH) is an autosomal recessive mucopolysaccharide storage disorder caused by deficiency of lysosomal alpha-l-iduronidase (IDU) A 16-month-old girl with MPS-IH was conditioned uneventfully with busulfan, cyclophosphamide and one dose of total body irradiation 300 cGY (bu/cy/TBI) for a matched unrelated donor (MUD) bone marrow transplantation (BMT). Broad-spectrum antibiotics were started on day +2 because of fever. Nasopharyngeal (NP) swab prior to conditioning was positive for parainfluenza type 3. On day +9 she developed stridor that was attributed to mucositis. However, a repeat NP swab was again positive for parainfluenza type 3 and ribavirin inhalation treatment was initiated on day +12. On day +15, there was sudden unexplained severe oxygen desaturation followed rapidly by cardiorespiratory arrest. She needed complete cardiopulmonary resuscitation. Fresh blood was noted during intubation. Complete blood count (CBC) and coagulation profiles are summarized in Table 1. Chest X-ray showed whitening of both lung fields with bilateral diffuse confluent pattern of air spaces. She received blood product support and ventilation in the pediatric intensive-care unit (PICU) and had no further pulmonary hemorrhages (PHs). She engrafted for white cells (defined as ANC count 40.5 Â 10 9 /l) on day +19. She was discharged home on day +40. Donor engraftment was successful based on DNA chimerism studies with a normal level of IDU enzyme up to a follow-up period of 7 years.
Patient 2A 23-month-old boy with MPS-IH was conditioned with the same protocol for a MUD BMT. On day -6, he became febrile and a blood culture from the central line was positive for Staphylococcus aureus. His treatment consisted of antibiotic therapy and removal of the central line. However, he remained persistently febrile until day +19 when he engrafted for white blood cells. The following day, there was sudden oxygen desaturation followed by cardiorespiratory arrest. Resuscitation included intubation at which time blood was again noted in the endotracheal tube. The CBC and coagulation profiles are illustrated in Table 1 and the chest X-ray demonstrated bilateral confluent airspace disease similar to patient 1. He continued to need ventilation support with platelet transfusions to keep the platelet count above 50 000/ml. A second life-threatening PH occurred 5 days after the first bleed while he was still on a ventilator. Ventilation continued for 14 days and he was extubated on day +33. DNA chimerism studies and measurement of IDU in peripheral blood leukocytes subsequently demonstrated graft loss and a second transplant was not performed. He is currently 10 years of age and continues to be followed by our metabolic team.
Patient 3An 11-month-old boy with MPS-IH was conditioned uneventfully with the same protocol for a MUD BMT. Prior to BMT he was diagnosed with hydrocephalus and a ventriculoperitoneal shunt was inserted. On day +2 broad-