Neuropathological and clinical correlations in Hurler disease

We report studies on two patients (1 and 2) with Hurler disease. They both had all of the non-neurological features of Hurler disease to a similar and extreme degree and similar signs of brain damage on computed tomography. However, intellectual function was unusually well-preserved in patient 1, but seriously and typically impaired in patient 2. The reason for this discrepancy has been investigated by reference to the neuropathological findings, the results of alpha-L-iduronidase assays using different substrates and comparisons to other cases (patients 3 and 4). We suggest that patient 1 is an unusual variant of the disease who may have had a very low residual alpha-L-iduronidase activity in neuronal cells only, and that this could not be demonstrated by either enzyme assays on whole brain using the 4-methylumbelliferyliduronide substrate (Crow et al., 1983) or in studies on fibroblast lysates using a radioactive disaccharide substrate.