Population Screening

Newborn Screening.

In the United States, every state requires that certain screening tests be done on all newborn infants. Interestingly, individual states vary significantly as to which screening tests they require. For instance, while it is mandatory to screen for PKU in every state, other relatively common inherited disorders, such as medium-chain acyl-CoA dehydrogenase deficiency and congenital adrenal hyperplasia, are only screened for in selected states. Furthermore, some private organizations offer an expanded selection of testing for genetic disorders in newborns beyond what individual states mandate.

Newborn screening is the only population-based type of screening for inherited disorders. One public health benefit of population-based screening means that everyone is tested. This is especially useful for studying inherited disorders, since it permits scientists to determine with great accuracy how frequently some inherited disorders occur in the general population.

In simple terms, there are two types of testing done for newborn screening: non-DNA-based testing and DNA-based testing. With DNA-based testing, an individual's DNA is tested directly. With non-DNA-based testing, two indirect methods are used: Enzymatic or electrophoretic testing methods are used to figure out whether an individual has an inherited disorder.

The most well-known newborn screening test is for PKU. PKU is an autosomal, recessively inherited metabolic disorder characterized by a lack or defect of phenylalanine hydroxylase, an enzyme involved in the metabolism of an amino acid called phenylalanine. Because this enzyme does not function properly, persons with PKU have a buildup of phenylalanine in their bodies, which results in severe mental retardation if untreated. Treatment currently involves dietary restriction of phenylalanine. Because phenylalanine is an essential amino acid (meaning that our bodies cannot make it, and it is essential for life), people with PKU cannot eliminate the substance entirely from their diet. Instead they must take care to modulate the amount they consume, because they cannot metabolize extra phenylalanine. Therefore, persons with PKU are usually under the care of a dietitian, who helps them to eat a balanced diet with the right amount of phenylalanine. Most importantly, by following the proper diet, individuals with PKU will not develop mental retardation.

Screening for PKU is done using the Guthrie test, a bacterial inhibition assay, a non-DNA-based (enzymatic) laboratory test. Another example of a non-DNA-based test is hemoglobin electrophoresis, which is done to determine the types of hemoglobin an individual carries. This information is a direct reflection of an individual's genetic makeup. Some other examples of disorders screened for, using non-DNA-based tests, include hypothyroidism, congenital adrenal hyperplasia and hemoglobinopathies (such as sickle cell disease and thalassemias). In contrast, DNA-based genetic testing is a relatively new clinical tool in newborn screening. In at least one state, DNA-based newborn screening is done for cystic fibrosis.

Carrier Testing.

In contrast to newborn screening, which is done on all newborns regardless of family history or ethnicity, carrier testing is aimed at a specific population that is viewed to be at high risk for a given disorder. In addition, carrier testing is always DNA-based, whereas newborn screening is typically non-DNA-based. Carrier testing is offered to determine if individuals carry a single non-working copy of a gene for a genetic disorder.

In general, individuals who carry one copy of a non-working gene will not have symptoms or signs of the disorder. When two individuals who are carriers for the same inherited disorder have a child, that child is at a 25 percent risk of inheriting a copy of the non-working gene from each parent, and will usually show symptoms and signs of the inherited disorder. Diseases that may be inherited in this way are called autosomal recessive disorders, and include sickle cell disease, Tay-Sachs disease, and cystic fibrosis.

In the late 1990s, a panel convened at the National Institutes of Health and recommended that carrier screening for cystic fibrosis be offered to a number of populations, including adults with a family history of the disease, the partners of people who had the disease, couples who were planning a pregnancy, and couples seeking prenatal testing. Newborn screening and general population screening, however, were not recommended.