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 marrow transplantation (BMT) more than 10 years ago, have recently had their α-L-iduronidase genotypes defined. Both patients, homozygous for the relatively common W₄₀₂X 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 W₄₀₂X, have an extremely severe 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 α-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 W₄₀₂X 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.