LONG-TERM CLINICAL-PROGRESS IN BONE-MARROW TRANSPLANTED MUCOPOLYSACCHARIDOSIS TYPE-I PATIENTS WITH A DEFINED GENOTYPE

Two mucopolysaccharidosis type I (MPS-I) patients, subjected to bone m arrow transplantation (BMT) more than 10 years ago, have recently had their alpha-L-iduronidase genotypes defined. Both patients, homozygous for the relatively common W(402)X mutation, received BMT when they we re 14 and II months of age, and are now 12 and 14 years old, respectiv ely. Untreated MPS-I patients, homozygous for W(402)X, have an extreme ly severe clinical phenotype with rapid clinical deterioration and dea th before 6 years of age. The 12-year-old patient, with limited mobili ty, is coping well at school, while the other patient is wheelchair-bo und with severe disability in his lower limbs, and attends a school fo r the physically handicapped. Both patients have less than normal inte lligence with slowly continuing losses. A third MPS-I patients, diagno sed at the age of 6 months, was felt, prior to BMT at 14 months, to ha ve a severe phenotype. Twelve years post-BMT, he is ambulatory, albeit with restricted movement, and has normal intelligence. This patient d id not have a defined MPS-I genotype and had alpha-L-iduronidase prote in and activity consistent with a less severe outcome than the first t wo patients. We conclude that BMT has significantly slowed down the cl inical regression of the W(402)X phenotype. We propose that if further gains are to be made, BMT should be performed within the first few mo nths of life. Early diagnosis is therefore essential.