Diagnosis of α-l-Iduronidase Deficiency in Dried Blood Spots on Filter Paper: The Possibility of Newborn Diagnosis

Mucopolisaccharidosis type I (MPS I), produced by a deficiency of α-l-iduronidase (EC 3.2.1.76) activity, can manifest three major clinical phenotypes: Hurler, Scheie, and Hurler-Scheie syndromes. The clinical phenotypes cannot be differentiated by routine biochemical diagnostic procedures. Mutation analysis allows the classification of some patients, but in most cases assignment to an MPS I type can be made only on the basis of clinical criteria (1). In the last few years treatment of MPS I became possible by bone marrow transplantation (2), enzyme replacement therapy (3), and gene transfer or gene modification (4). The effectiveness of these therapies, particularly for MPS involving the central nervous system, may rely heavily on early diagnosis of the disorder. An additional consideration critical to bone marrow transplantation is that early diagnosis of the patient will allow clinicians to take advantage of the period of natural suppression of the immune system of the neonate to maximize the chances of a successful engraftment. Except for those cases with a family history of the disease, presymptomatic detection of MPS I can be achieved only by newborn screening (5). In any case, a simple technique suitable for dried blood spots on filter paper (DBFP) is needed. The most widely used specimens for the diagnosis of iduronidase deficiency have been homogenates of cultured fibroblasts or leukocytes. Analysis of iduronidase in leukocytes is preferred because it avoids time-consuming and costly tissue culture. However, isolation of leukocytes from venous blood is also time-consuming. Additionally, transport of these samples from one city or country to another is difficult. Several microtests for the assay of iduronidase in plasma and/or leukocytes have been published (6)(7), but these methods have not been applied to DBFP. We describe here an adaptation …