Welcome to the ACMG Knowledge Nugget on newborn screening for hemoglobin S.S. disease, more commonly known as sickle cell disease. This activity is intended for educational purposes only. Neither I nor the planning committee have any disclosures. This session is approved for 0.25 CME. To obtain CMEs for this activity, you will need to pass the quiz with a score of at least 80% and complete the evaluation. This session is a companion to the Hemoglobin S.S. Disease Act Sheet, which is freely available at www.acmg.net slash ACT. Act Sheets are intended to be immediate resources for providers who encounter positive newborn screening results. Please keep in mind that a newborn screening result is just the first step in the diagnostic process. Further testing and evaluations are needed to determine if the newborn has the disease, a true positive result, or is unaffected, a false positive result. The Act Sheets are intended to provide an overview of the diseases identified by newborn screening and clear next steps for the management of a positive newborn screening result. This session will cover background information on hemoglobin S.S. disease, including clinical features and the underlying genetic cause, actions a primary care provider needs to take upon receiving a screen positive test result for hemoglobin S.S. disease, clinical considerations, and supplemental resources. Hemoglobin S.S., also known as sickle cell disease, is a genetic condition caused by pathogenic variants found in the beta hemoglobin or HBB gene. This gene is responsible for making hemoglobin molecules, which in normal adult hemoglobin or hemoglobin A, are composed of two alpha globin chains and two beta globin chains. In sickle cell disease, the beta globin chains are altered. This changed hemoglobin is known as hemoglobin S. The hemoglobin S variant causes changes to the shape of hemoglobin from the normal donut shaped red blood cells into a sickle or crescent shape. This sickle shape decreases the ability for red blood cells to carry oxygen and increases the chances of these cells getting stuck and blocking blood flow. This also can cause the premature breakdown of red blood cells. Sickle cell disease is found in all races and ethnicities. Infants born with sickle cell disease are typically asymptomatic at birth, with signs and symptoms appearing as beta globin chains begin to develop in the first year of life. Signs and symptoms of hemoglobin S.S. are highly variable, ranging from mild symptoms to life-threatening symptoms and frequent hospitalizations. Characteristic signs of sickle cell disease are anemia or low red blood cell counts, periodic episodes of pain called pain crises, and frequent infections. Anemia can cause fatigue, shortness of breath, delayed growth, and jaundice or yellowing of the skin and eyes. Stroke, organ failure, and pulmonary hypertension can also occur. Without proper treatment, additional problems including splenic sequestration, pneumonia, acute chest syndrome, swelling of the fingers and toes, dactylitis, and osteonecrosis can occur. Sickle cell disease is inherited in an autosomal recessive manner, meaning that only infants with a pathogenic variant in both of their HBB genes will be affected. Parents with a child with sickle cell disease are carriers and, in most cases, are usually unaffected, but have a 25% recurrence risk with any future children they have together. All states in the United States provide newborn screening for sickle cell disease. A good resource for checking a state's newborn screening panel is the newbornscreening.hrsa.gov website. Screening for sickle cell disease is performed by examining different levels of hemoglobin molecules. Studies with the hemoglobin SS form of sickle cell disease typically have hemoglobin S and hemoglobin F, or fetal hemoglobin, with little to no presence of adult hemoglobin A. Now that you have an understanding of what sickle cell disease is, let's talk about what to do if you have a patient screen positive for sickle cell disease during newborn screening. You will need to take the following actions. First, contact the family and do the following. Inform them of the newborn screening result and that more testing is needed to determine if their child does or does not have sickle cell disease. Ascertain clinical status, keeping in mind that most newborns will be asymptomatic. Evaluate the child for splenomegaly and send a CBC. Administer prophylactic penicillin. Provide the family with basic information about sickle cell disease. Second, take a family history. Because sickle cell disease is inherited in an autosomal recessive manner, it is common for there to be no known family history of sickle cell disease. Third, arrange a referral to a sickle cell disease specialist for a comprehensive clinical evaluation, discussion of the treatment plan, and genetic counseling. The specialist is typically a pediatric hematologist. The clinical evaluations should include a comprehensive physical assessment by an experienced sickle cell disease specialist. Fourth, working with the appropriate specialist, take steps to ensure confirmation of the newborn screening result. Confirmatory testing includes isoelectric focusing, high-performance liquid chromatography, or capillary zone electrophoresis. Fifth, report the final diagnostic outcome back to your state newborn screening program. The goal of treatment for sickle cell disease is to prevent the health complications that are caused by this condition. Comprehensive care is important to prevent the life-threatening complications of sickle cell disease. This includes modified immunization schedules due to the increased risk of infection in those with sickle cell disease, prophylactic antibiotics to prevent the frequent infections, therapeutic medications such as hydroxyurea and analgesics, and prompt recognition and treatment of vaso-occlusive events. Urgent evaluations of fevers greater than or equal to 38.5 degrees Celsius, or 101 degrees Fahrenheit, and early screening for organ damage are also important. As you continue to care for your patient with a positive newborn screen for sickle cell disease, it is likely additional questions and concerns will come up. Here are some resources where you can obtain information on sickle cell disease, appropriate laboratories and tests, and genetic specialists. Before we end today's session, let's have a quick review. First, hemoglobin SS, also known as sickle cell disease, is a serious condition. An identification of affected individuals is essential for the administration of early preventative measures. Second, newborn screening helps with early identification of those with sickle cell disease. As most newborns will be asymptomatic, it may not have signs or symptoms until they are very sick. Third, ACT sheets are freely available on the ACMG website to review in the event of a screen-positive result. In addition to sickle cell disease, ACT sheets are available for many other conditions that can be identified through newborn screening.

newborn screening

sickle cell disease

genetic cause

management steps

health complications