As a product manager, one of my responsibilities is to exhibit at various scientific conferences to promote and advertise products for genomic DNA extraction. Less than three months into the job, I attended the American College of Medical Genetics (ACMG) conference to promote a new product we had just launched for DNA extraction from blood and cells. After hours of talking to people about the features and benefits of my fancy new kit, a gentleman walked by my booth, looked at the demo on the table, and asked me to explain how it worked. Excited that I finally found an interested scientist, I enthusiastically went into my spiel, but as it turned out, I was the one who did most of the listening.

That gentleman was Dr. Kenneth Pass from the NYS Dept of Health, and at that time, head of the newborn screening program for New York State. During our fifteen minute conversation, Ken educated me on the challenges and benefits of newborn screening programs throughout the world. I was immediately inspired, to such an extent that newborn screening continues to be an area that fuels my passion for science and discovery. In this article, I’d like to pass some of that education, and hopefully inspiration, to you.

Of the four million babies born in the USA each year, several thousand will be born with one of an array of severe disorders for which early detection and treatment is crucial for cure or management. And newborn screening is designed to to just that: to quickly identify those babies who have such disorders so that treatment can be administered.

The first newborn disease ever screened for was Phenylketonuria (PKU). PKU is the inability to metabolize phenyalanine and causes mental retardation if the child is not put on a restricted diet as soon as possible. With the correct diet in place, a child can grow up completely normal and healthy with no signs of any disease. This is a classic example of early detection saving lives.

The ACMG recommends a panel of 29 detectable and treatable disorders to be screened for in newborn babies. The tragedy is that with 4 million babies born each year in the US, not all babies get the same level of screening. While most states are following the ACMG guideline for 29 diseases, two states, Pennsylvania and Arkansas, test for less than 10 diseases, and a handful are testing between 10-20 diseases. In poorer countries, the level of testing is minimal, if any testing is carried out at all.

All newborn screening is performed using blood spots punched from blood collected on a Guthrie card within 48 hours of birth. These samples sent to labs where screens, mostly mass spectroscopy-based, are carried out to detect any disorders.

The difficulty with the mass spec methods for newborn screening is, you’ve guessed it, cost. A mass spec instrument costs as much as half a million dollars and requires a full-time PhD to operate. In many of the states, and other countries, the amount of resources needed to become compliant with the ACMG recommendation compared to birth rates makes it difficult to keep up with the larger states like New York and California.

Using molecular techniques, groups like Ken’s are revolutionizing this field by making newborn screening simpler, cheaper and more widely available. An example is the development work they are doing for cystic fibrosis.

Cystic fibrosis is the most common inherited fatal disease and affects 2500 babies a year in the US with a carrier rate of 1 in 20 people. Over 1000 different mutations have been identified in the CFTR (cystic fibrosis transmembrane conductance regulator) gene, yet 79% of the CF cases can be attributed to an amino acid substitution of phenyalanine at position 508 in the protein. Because so many mutations are possible for the disease phenotype, and because the CF gene is well characterized, it makes a perfect candidate for genetic testing on the molecular level. Using multiplex PCR or microarray techniques, many companies are offering standardized tests for CF screening that can detect the 40 most common mutations and provide the specific genotype of the individual. The reason CF is on the newborn screening panel is because early nutritional therapy can play an important role for survival to fight the bacterial lung diseases that develop due to CF.
Tests for new diseases are also being investigated. An example is Severe Combined Immunodeficiency Disease (SCID) (AKA bubble boy disease). Scientists at the Centers for Disease Control (CDC), UCSF, and several state public health laboratories are studying a method that that uses real-time PCR to screen for the absence or presence of T-cell precursors as a way for detecting immunodeficiency caused by the SCID mutation. A lack of T-cell precurors (called TRECs) indicates the presence of the disease. SCID is an example of a disease that can be completely cured if a bone marrow transplant is given with 2 weeks of birth. If it’s not detected, it means hundred’s of thousands of dollars will be spent trying to maintain some form of quality of life for a very sick child.

As these PCR-based tests advance, new techniques such as comparative genomic hybridization (CGH) array and next generation sequencing are appearing on the horiozon and offer even more promise. By allowing us to rapidly decipher whole genomes these techniques are allowing us to not only learn the cause of many of these diseases on the molecular level, but also to develop DNA-based tests for detecting a disease based on the presence of specific single nucleotide polymorphisms (SNPs) responsible for the disease.

As medicine becomes more personalized, the next wave of testing may very well be whole genome sequencing at birth followed by real-time PCR to test for the presence of specific mutations.

While the new generation of rapid genomic technology is still in its infancy, many groups are working to equalize and standardize newborn screening world wide so every child has an equal chance for a healthy start to life. The Newborn Screening Translation Research Initiative headed by Dr. Bob Vogt and the Centers for Disease Control in Atlanta is one program among many that is dedicated to the cause of progress and innovation in newborn screening. For more information on the newborn screening programs in your area, visit your local public health lab webpage or consider attending the Newborn Screening and Genetic Testing Symposium in 2008.

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About the Author

Suzanne Kennedy