Welcome to the A C MG Knowledge nugget on Newborn screening for Kreb a 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 C m e. To obtain CES for this activity, you'll need to pass the quiz with a score of at least 80% and complete the evaluation. This session is a companion to the KRAB A Disease Act. Sheets, which are freely available at www.acmg.net/ct app 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 Krabbe 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 CRE A disease, clinical considerations and supplemental resources. Cree Disease, also known as glo. Boid cell leukodystrophy is a lysosomal disease caused by pathogenic variants found in the GAL C gene, which leads to a decrease in galacto Cerebro tase enzyme activity. This decreased activity results in the accumulation of cycline, which impairs the formation of myelin and leads to severe life-limiting neurological symptoms. The presentation of krabbe disease is clinically variable and ranges from a rapidly progressive infantile form to more slowly progressive later onset forms. The infantile form of CRE a disease is the most common in symptoms usually begin during the first year of life. Early symptoms include irritability, muscle weakness, feeding problems, and spasticity, life expectancy. For the infantile form of CRE, a disease is severely limited. The those with later onset CRE a disease will have much slower progression of disease symptoms with vision and walking difficulties being the most common initial symptoms. Kreb a disease is inherited in an autosomal recessive manner, meaning that only infants with a pathogenic variant in both of their GAL C genes will be affected. Parents of an infant or child with Krabbe disease are carriers and are unaffected, but heavy 25% or one in four recurrence risk with any future children they have together at this time. Not all states provide newborn screening for CRAB a disease. A good resource for checking a state's newborn screening panel is the newborn screening.hrsa.gov website in the states that do screen for creb. A disease testing is generally performed by examining levels of the GALACTO Cerebro tase enzyme, which is decreased in individuals with CRE a disease. Some programs also examine the levels of CYCLINE as a second tier test to help improve screening differentiate between forms of CRE a disease and rural out cases of pseudo deficiency. Pseudo deficiency, which is commonly seen in lysosomal disorders, means that an infant's galacto cerebro sin enzyme levels appear low upon testing, but this decreased activity does not cause disease. Follow-up testing will demonstrate normal psychos scene levels. These infants do not have and will never develop Cree disease. Now that you have an understanding of what Cree disease is, let's talk about what to do. If you have a patient screen positive for Cree disease, do 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 the disease. Ascertain clinical status. No clinical signs are expected in the neonatal period. Provide the family with basic information about Cree disease. Second, take a family history. Because Cree disease is inherited in an autosomal recessive manner, it is common for there to be no known family history of krabbe disease. Third, arrange an immediate referral to a Krabbe disease specialist for genetic counseling, a comprehensive clinical evaluation and discussion of treatment options. The specialist could be a pediatric geneticist, neurologist, or transplant specialist. The clinical evaluations should include a comprehensive physical assessment by an experienced creb, a disease specialist. Fourth, working with the appropriate specialist take steps to ensure biochemical and or molecular confirmation of the newborn screening result. Confirmatory testing includes galactose, Cerebro enzyme analysis, psychos analysis, and G C gene sequencing fifth report the final diagnostic outcome. Back to your state newborn screening program. The only available treatment option for Creb a disease is hematopoietic stem cell transplantation. This treatment is most effective if done before 30 days of life in the infantile form and prior to the onset of clinical symptoms in the later onset forms. Gene therapy clinical trials may also be available as you continue to care for your patient with a positive newborn screen. For Creb a disease, it is likely additional questions and concerns will come up. Here are some resources where you can obtain information on creb a disease appropriate laboratories and tests and genetic specialists. Before we end today's session, let's have a quick review. First, KRE Bay Disease is a serious condition and identification of affected individuals is essential for administration of early treatment. Second, newborn screening may identify both the infantile and later onset forms of krabbe disease. Third act sheets are freely available on the A C M G website to review in the event of a screen positive result. In addition to Creb a Disease Act, sheets are available for many other diseases that can be identified through

newborn screening

Krabbe Disease

positive screening result

GALC gene

lysosomal disease