A few years later, her uncle, Dr Robert Guthrie, an American microbiologist, published his seminal paper on the

feasibility of mass screening for PKU, using a bacterial inhibition assay and dried blood spot (DBS) samples. This innovation can be regarded as the birth of newborn screening (NBS). Over the last 50 years, NBS has been an PKI587 acclaimed success, and many thousands of children have been saved from devastating effects of severe inborn metabolic disorders, congenital endocrinopathies, hemoglobinopathies, and other genetic disorders because of early diagnosis of their conditions. Many countries Inhibitors,research,lifescience,medical across the globe have made NBS mandatory.1 The expansion of a national NBS panel inevitably presents many scientific, technical, ethical, and policy issues that must be addressed prior to the addition of a new entity to the test panel. In general, the common criteria for including a disease in NBS are that 1) the prevalence of the disease justifies the costs involved;

2) the disorder is not Inhibitors,research,lifescience,medical readily identified by means of physical Inhibitors,research,lifescience,medical examination; 3) the disease must cause serious medical complications; 4) early diagnosis and treatment of the disease improves prognosis and leads to an acceptable outcome; and 5) the screening methodology is sensitive, specific, economic, validated, and available.2 NBS is of utmost importance in counties such as Israel, where the high rates of consanguineous marriages make inherited diseases much more common than in other parts of the world.3 For example, genetic disorders, such as congenital hypothyroidism,4 glucose-6-phosphate dehydrogenase Inhibitors,research,lifescience,medical deficiency,5 and PKU,6 have been found in a relatively high frequency in both the Israeli Jewish and non-Jewish communities. Thus far, the Israeli NBS program includes PKU, congenital hypothyroidism, congenital adrenal hyperplasia,

maple syrup urine disease, Inhibitors,research,lifescience,medical homocystinuria, tyrosinemia, methylmalonic acidemia, propionic acidemia, glutaric aciduria, medium- and very-long-chain acyl-CoA dehydrogenase deficiency, and a few other metabolic diseases. Another important disease that should be considered for inclusion in the Israeli NBS is severe combined immunodeficiency (SCID).7 SCID found encompasses a heterogeneous group of genetic disorders characterized by thymic dysplasia and arrest in T lymphocyte maturation. There is also variable expression of B and natural killer (NK) cells, and patients are categorized into either SCID with absence of T lymphocytes but presence of B lymphocytes (T-B+ SCID) or SCID with absence of both T and B lymphocytes (T-B- SCID). Regardless of the immunologic phenotype, patients with SCID present with similar clinical features, including early-onset severe respiratory tract infections, chronic diarrhea, and failure to thrive.