Expanded Newborn Screening

By Erica Wright, MS, CGC, Expanded Newborn Screening Coordinator
Inherited Metabolic Diseases Clinic, The Children’s Hospital

In July 2006, both Colorado and Wyoming expanded their newborn screening panels from just seven disorders to over 30 disorders. In recent years, new technology using tandem mass spectrometry (MS/MS) allowed for newborn screening to drastically change. The newly added disorders are all inborn errors of metabolism including amino acidemias, organic acidemias and disorders of fatty acid oxidation. The addition of over 25 disorders to the newborn screening panel now fulfills both the recommendations of the March of Dimes and the American College of Medical Genetics (ACMG). The goal of newborn screening remains the same: early detection of children at increased risk for severe diseases in order to promptly start treatment that prevents metabolic crises and irreversible sequelae.

Historically, newborn screening began in the United States in the 1960s after Dr. Robert Guthrie discovered that PKU could be diagnosed from a single drop of blood on filter paper using a bacterial inhibition assay. Massachusetts passed legislation in 1963 mandating newborn screening for PKU and many states quickly followed. The success of PKU testing led to the development of additional newborn screening techniques for other disorders. Traditionally, screening for each disorder required a separate test and a separate disk punched from the newborn screening card. This testing method limited the number of disorders that each state could have on their panel with states often adding new disorders to their panels one by one. The advent of MS/MS has changed the “face” of traditional newborn screening by allowing numerous disorders to be screened for in one test with only one blood spot.

Since the implementation of expanded newborn screening, the Inherited Metabolic Diseases (IMD) Clinic has identified over 35 newborns with disorders now included on the newborn screening panel. This includes seven infants that were found to have Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD). The IMD clinic did not have to wait long to identify the first patient with MCADD. Two weeks into the program, the first baby was identified. MCADD is the most frequent disorder detected by MS/MS with frequency of one in 15,000, comparable to the frequency of PKU. Typical features of MCADD, like many other disorders of fatty acid oxidation, include Reye-like syndrome with hypoketotic hypoglycemia, liver dysfunction, hyperammonemia and brain edema. Undiagnosed, mortality is between 20-25 percent with significant morbidity. With treatment, mortality is reduced to almost zero with significant reduction of morbidity.

Treatment is relatively simple:

• Avoidance of fasting
• Early intervention for acute illness including IV dextrose, and
• Carnitine supplementation is often used to prevent secondary carnitine deficiency.

Early Identification is Key

Many of the first patients identified by newborn screening are stories of success: babies diagnosed with life-threatening and neurologically devastating disorders prior to the onset of symptoms with necessary treatment started promptly. This is not always the case. Many of the disorders on the newborn screening panel can present early in an infant’s life, often by the end of the first week or even possibly before the newborn screen is even obtained. These disorders are considered to be “metabolic emergencies” since immediate action may be required.

For some disorders, such as Maple Syrup Urine Disease (MSUD), Methylmalonic Acidemia, Very Long Chain Acyl-CoA Dehydrogenase (VLCAD) Deficiency to name a few, it becomes imperative that the newborn screen is obtained and resulted within the first week of life. Currently, most hospitals in this region are sending the newborn screening cards to the state lab by regular mail, thus increasing the time it takes for results to be available. The state lab is able to turn around results within 24 hours of receiving the newborn screening card. However, the majority of newborn screening cards are reaching the state lab via regular mail when the baby is already over a week of age even though the cards were obtained at the mandated age of 24 to 72 hours of life. The use of courier service will expedite the newborn screening results by multiple days and thus results could be called out within the goal time of five days of life. Treatment can then be initiated presymptomatically thus drastically altering the outcome for infants affected with many of these inborn errors of metabolism.

Introducing Report Cards

In order to address the issue of timeliness of the newborn screen, the Colorado State Newborn Screening Laboratory will introduce report cards to the area hospitals in coming months. The report card will grade hospitals on such things as number of unsatisfactory samples, completeness of demographic information on the newborn screen card, and most importantly, timeliness of both sample collection and transport to the state lab. The goal of the report cards is to strengthen compliance of area hospitals adhering to standards outlined by both the state laboratory and the Inherited Metabolic Diseases Clinic.

Overall, the expansion of newborn screening over the last year and a half has been quite successful. Multiple babies have been identified with life-threatening inborn errors of metabolism and have received prompt treatment keeping these children healthy and neurologically intact. The most important thing for providers to recognize is that newborn screening is an integrated system consisting of the birth hospitals, state laboratory, primary care physicians and the follow-up laboratory and appropriate clinics. Any breakdown in the system can completely negate the benefits of newborn screening.

This includes:

• Delay in collection of NBS card
• Incorrect or mishandling of NBS card
• Delay in transit of NBS card
• Incomplete demographic information
• Delay of necessary action by any of the parties involved

Therefore, in the age of expanded newborn screening it becomes even more imperative that all components of newborn screening system are working smoothly and proficiently so that infants affected with these rare metabolic disorders can receive necessary and life-saving treatment as quickly as possible.