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Long‐term clinical progress in bone marrow transplanted mucopolysaccharidosis type I patients with a defined genotype
Author(s) -
Hopwood J. J.,
Vellodi A.,
Scott H. S.,
Morris C. P.,
Litjens T.,
Clements P. R.,
Brooks D. A.,
Cooper A.,
Wraith J. E.
Publication year - 1993
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/bf00711520
Subject(s) - mucopolysaccharidosis type i , medicine , hurler syndrome , pediatrics , genotype , bone marrow transplantation , mucopolysaccharidosis , transplantation , ambulatory , enzyme replacement therapy , disease , genetics , biology , gene
Summary 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 W 402 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 W 402 X, 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 W 402 X 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.