New Cystic Fibrosis Screening - July 2007
Newborn screening has been a reality for many diseases for quite some time. This month, two new items were added: Cystic Fibrosis (CF) and biotinidase deficiency.
Newborn screening for CF was mandated by the California legislature in 1999. July 1, 2007 marked the official launch date for the program. This time lag permitted extensive preparation to develop a new, four-step screening method to fit our diverse racial mix better than standard three-step processes in other states. We completed three studies to learn more about our California population and devise a plan that would be most effective. Problems with other state screening programs included large numbers of false positives with marked increases in sweat testing and counseling requirements for families that were carriers rather than affected individuals. California was eager to identify real cases and limit the number of false positives/negatives.
The racial mix in California includes large numbers of Caucasians, Asians, Latinos and African Americans. The newly diagnosed CF population in California does not match the demographics because the rate in Asians remains so low (estimate 1:50-90,000). The three studies performed to determine the test sequence in California were:
1. Determination of usefulness of the blood spot for immuno-reactive trypsin (IRT) detection on known cases of CF in California from 1982 on. This permitted calculation of the best IRT cut off point for our state.
2. Determination of the most prevalent severe CF mutations in Latinos and Blacks in California. This resulted in the 38 mutation panel to be used for California screening.
3. Determination of the error rate in transcribing information into CF databases and records. This resulted in the plan for the genetic information to be directly entered into the new state database by the Genetic Disease Branch of DHS. All other data for the database will be entered by the contracted CF centers.
The Final Four-Step Cystic Fibrosis Screening Plan
Step One: A single Guthrie blood spot card is used from all newborns. Those with the highest 2.2% IRT result are considered high risk. The expected rate of false negatives (babies who are not identified with cystic fibrosis by the screen but who actually have it) is four per year.
Step Two: CF mutation panel for 38 common mutations. It is expected that most of the easily identified mutations will be discovered here. Mailers will be sent to the families and PMD informing them that the patient has CF and needs to be quickly referred to a CF center. Some patients will only have one gene defect discovered and move on to step three.
Step Three:CF sequencing for the high-risk patients with only one mutation on the 38 panel. This will find a few more patients with two identifiable mutations. Again, mailers will go to patients and families. Those identified as cases will be labeled as CF and referred to CF centers. Those still with only one mutation identified will be carriers and phone genetic screening recommended.
Steph Four: Sweat testing is the final step. The CF center will arrange it for those with two identified mutations to confirm results. Sweat testing for symptomatic children who were missed during screening and infants thought to be carriers with symptoms will also be expected.
Please see the algorithm, which lists the CF cases versus the total births for the year and expected fallout based on this testing scheme. This model should decrease our false identifications and spend fewer taxpayer dollars, while meeting the goals of newborn screening.
Thank you in advance for early referral to the California Pacific's CF Center. We look forward to working with you as we begin a new chapter caring for patients identified by screening who are still healthy. It is our goal to keep them healthy along with you.
This information provided by Karen A. Hardy, M.D. and the Cystic Fibrosis Center Team. Dr. Hardy is available to answer questions and can be reached at khardy@mail.cho.org or by phone (back office line) at 510-428-3885 x5733. California Pacific Medical Center Department of Pediatrics.