J. lnher. Metab. Dis. 16 (1993) 1024-1033 © SSIEM and Kluwer Academic Publishers. Printed in the Netherlands Long-term Clinical Progress in Bone Marrow Transplanted Mucopolysaccharidosis Type I Patients with a Defined Genotype J. J. HOPWOOD 1, A. VELLODI 2, H. S. SCOTT 1, C. P. MORRIS 1, T. LITJENS 1, P. R. eLEMENTS 1, D. A. BROOKS 1, A. COOPER 3 and J. E. WRAITH 3 1Lysosomal Diseases Research Unit, Department of Chemical Pathology, Adelaide" Children's Hospital, North Adelaide, South Australia 5006, Australia; 2Bone Marrow Transplant Unit, Westminster Children's Hospital, London; 3Willink Biochemical Genetics Unit, Royal Manchester Children's Hospital, Manchester, UK Summary: Two mucopolysaccharidosis type I (MPS-I) patients, subjected to bone marrow transplantation (BMT) more than 10 years ago, have recently had their ~-L-iduronidase genotypes defined. Both patients, homozygous for the relatively common W4o2 X mutation, received BMT when they were 14 and 11 months of age, and are now 12 and 14 years old, respectively. Untreated MPS-I patients, homozygous for WgozX, have an extremely se-~ere clinical phenotype with rapid clinical deterioration and death before 6 years of age. The 12-year-old patient, with limited mobility, is coping well at school, while the other patient is wheelchair-bound with severe disability in his lower limbs, and attends a school for the physically handicapped. Both patients have less than normal intelligence with slowly continuing losses. A third MPS-I patients, diagnosed at the age of 6 months, was felt, prior to BMT at 14 months, to have a severe phenotype. Twelve years post-BMT, he is ambulatory, albeit with restricted movement, and has normal intelligence. This patient did not have a defined MPS-I genotype and had ~-L-iduronidase protein and activity consistent with a less severe outcome than the first two patients. We conclude that BMT has significantly slowed down the clinical regression of the W4o2X phenotype. We propose that if further gains are to be made, BMT should be performed within the first few months of life. Early diagnosis is therefore essential. The mucopolysaccharidoses (MPS) are a group of genetic lysosomal storage disorders caused by a deficiency of any one of a number of enzymes involved in the lysosomal degradation of mucopolysaccharides (Neufeld and Muenzer 1989; Hopwood and Morris 1990). Hurler syndrome has been considered the archetype for all MPS and has been systematically named mucopolysaccharidosis type I (MPS-I, McKusick 252800). Generally, patients with Hurler syndrome have a severe, progressive disorder resulting in death, usually before 10 years of age. These patients are reported to have MS received 10.5.93 Accepted 30.6.93 1024