Transplant Outcomes in Leukodystrophies
Section snippets
Metachromatic Leukodystrophy
The term “metachromatic” refers to the staining pattern of sulfatides that accumulate in the cells of individuals with metachromatic leukodystrophy.8 Metachromatic leukodystrophy is an autosomal recessive lysosomal disorder caused by a defect in ARSA activity. Defects in the ARSA gene result in accumulation of the substrate cerebroside 3-sulfate, which is found primarily in myelin membranes.9 The inability to degrade substrate leads to demyelination of the white matter of the CNS, as well as
Globoid Cell Leukodystrophy
The disorder known as globoid cell leukodystrophy was initially described in 1916 by Krabbe, and hence is also called Krabbe disease.28 The term “globoid cell” refers to multinuclear macrophages present within the brain characteristically seen in this disorder. In 1970 the enzyme defect responsible for globoid cell leukodystrophy was identified as galactocerebroside β-galactosidase (GALC), a lysosomal enzyme;29 this enzyme is also commonly referred to as galactocerebrosidase. The gene was
Clinical Manifestations of Adrenoleukodystrophy
Adrenoleukodystrophy was initially described in 1923 by Siemerling and Creutzfeld as a condition characterized by hyperpigmentation and central nervous system demyelination. In 1976 Igarashi and colleagues observed that saturated very–long-chain fatty acids, such as hexacosanoic acid (C:26:0), accumulate in the brain and adrenal tissue of patients with adrenoleukodystrophy.48 Later, it was shown that excess very–long-chain fatty acids are also present in plasma,49 especially C24 and C26 fatty
Current Controversies in Hematopoietic Cell Therapy of Leukodystrophies
Despite the experience of several decades in the use of transplantation for inherited metabolic disorders affecting the CNS, there is much that remains unclear, including the following:
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The majority of physicians transplanting these patients would agree that, with current techniques, outcomes are poor for transplantation for symptomatic infantile globoid cell leukodystrophy and metachromatic leukodystrophy. However, whether patients transplanted very early in life (several weeks of age) will
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