The goal of newborn screening is to detect potentially fatal or disabling conditions in newborns, thereby providing a window of opportunity for early treatment, often while the child is still asymptomatic. Such early detection and treatment can have a profound impact on the clinical severity of the condition in the affected child. If left undiagnosed and untreated, the consequences of the targeted disorders can be dire, many causing irreversible neurological damage, intellectual, developmental and physical disabilities, and even death. In 2006, the American College of Medical Genetics (ACMG) developed newborn screening guidelines that recommend that all newborn infants be screened for 31 """"""""core conditions"""""""" and that 27 secondary conditions identified during the core evaluations be reported. These recommendations have been accepted by the HHS Secretary's Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) (authorized by the Children's Health Act of2000), and by the Secretary of HHS. Most states now use this or very similar panels for newborn screening. Currently, there are thousands of rare disorders that have been identified and hundreds that could potentially benefit from newborn screening. It has become evident however, that a major impediment to implementing new technologies in high throughput newborn screening laboratories is the ability to provide evidence of the feasibility of the assay, both scientifically and logistically, in a timely manner. A majority of disorders considered for newborn screening are rare diseases where the likelihood of detecting cases during standard newborn screening in a single laboratory is very low. For example, Michigan has 114,159 annual births and Severe Combined Immune Deficiency has a reported prevalence of I :100,000. For this reason collaborative efforts, implemented across multiple states or newborn screening laboratories, are necessary for the successful identification, development, and implementation of new assays. Pompe disease is one of at least 40 different types of Lysosmal Storage Disorders (LSDs). Pompe disease leads to a deficiency of the enzyme acid ?-glucosidase (GAA), resulting in the accumu lation of lysosomal glycogen ultimately leading to tissue damage. All individuals with Pompe disease share the underlying GAA enzyme deficiency however, variability in enzyme activity leads to a broad spectrum of illness. Pompe disease is generally classified into two broad categories, infantile and late-onset disease. Infantile-onset Pompe disease is the most severe form of the disease. It can be further divided into the classic form, with profound and progressive hypotonia and cardiomyopathy, and death in the first year of life. The non-classic infantile form is not associated with cardiomyopathy and survival may be longer. Individuals with late-onset disease may not develop clinically significant weakness until later in childhood or as adults. This form of Pompe disease is associated with progressive weakness. Premature death can occur in middle age or older ages due to respiratory failure. Late-onset Pompe disease varies in age of onset and degree of illness. Late-onset Pompe disease can also be associated with specific types of cardiac involvement. It must be noted that at the time of diagnosis and through the first year of life, it may be difficult to classify cases, which can make the description of ongoing prospective case-finding activities challenging to describe.
