MIXED DONOR CHIMERISM AND LOW LEVEL IDURONIDASE EXPRESSION MAY BE ADEQUATE FOR NEURODEVELOPMENTAL PROTECTION IN HURLER SYNDROME

Hurler syndrome is a lysosomal storage disease resulting in fatal cardiac or neurologic sequelae unless alpha-iduronidase production is reconstituted with hematopoietic stem cell transplantation. We report on a 4-year, 6-month-old boy with mixed donor chimerism and low enzyme levels but a normal neurodevelopmental trajectory. (J Pediatr 2005;147:106-8) Children with Hurler syndrome lack the lysosomal enzyme alpha-L-iduronidase. This results in glycosaminoglycan(GAG) accumulation with progressive mental retardation and death.1,2 Recombinant alpha-L-iduronidase appears toameliorate some of the systemic effects in Hurler syndrome, but hematopoietic stem cell transplantation remains the only means of preventing the neurologic deterioration.3 Children with Hurler syndrome have normal intelligence at birth, but on average their IQ declines by 2 standard deviations within the first 2 years of life (30-point decrease in IQ).4 The negative correlation between age and IQ has been found to be significant (r = 20.82, P #.0003).2 Good neuropsychological outcomes after bone marrow transplantation (BMT) are dependent on multiple factors including age at transplantation (<24 months), mental developmental indexes>70 before transplantation, adequate engraftment (as measured by full donor chimerism), and posttransplantation iduronidase activity.4-6 We report the case of a patient with Hurler syndrome in whom a good neurologic outcome was achieved in spite of poor sustained engraftment and very low serum alpha-L-iduronidase activity after BMT. CASE REPORT At 9 months of age, the patient presented with coarse facies and a lumbar gibbus. He had dysostosis multiplex and a positive mucopolysaccharide (MPS) screen result. Hurle