Welcome to the ACMG Knowledge Nugget on newborn screening for biotinidase deficiency. 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 Biotinidase Deficiency Act Sheet, which is freely available at www.acmg.net.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 biotinidase deficiency, including clinical features and the underlying genetic cause, actions a primary care provider needs to take upon receiving a screen positive test result for biotinidase deficiency, clinical considerations, and supplemental resources. Biotinidase deficiency is a genetic disorder caused by pathogenic variants found in the BtD gene, which leads to decreased biotinidase enzyme activity and the inability to recycle biotin, a B-complex vitamin. This results in decreased levels of biotin and the disruption of several biotin-requiring enzymes. There are two types of biotinidase deficiency, severe, also called profound biotinidase deficiency, and mild, also called partial biotinidase deficiency. In both types, symptoms do not usually appear until a few months of life to early childhood. Early signs of profound biotinidase deficiency include episodic hypoglycemia, lethargy, and hypotonia. Untreated biotinidase deficiency can lead to developmental delay, seizures, hair loss or alopecia, and hearing and vision loss. However, biotinidase deficiency is easily managed and normal health outcomes are expected with treatment. Biotinidase deficiency is inherited in an autosomal recessive manner, meaning that only infants with a pathogenic variant in both of their BtD genes will be affected. Parents with a child with biotinidase deficiency are carriers and are unaffected, but have a 25% recurrence risk with any future children they have together. All states in the United States provide newborn screening for biotinidase deficiency. A good resource for checking a state's newborn screening panel is the newbornscreening.hrsa.gov website. Screening for biotinidase deficiency is performed by examining levels of the biotinidase enzyme, which is decreased in individuals with biotinidase deficiency. Screening may detect both profound and partial biotinidase deficiencies. Now that you have an understanding of what biotinidase deficiency is, let's talk about what to do if you have a patient screen positive for biotinidase deficiency 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 biotinidase deficiency. Ascertain clinical status. Pay close attention to signs like poor feeding, lethargy, and jaundice. Provide the family with basic information about biotinidase deficiency. Second, take a family history. Because biotinidase deficiency is inherited in an autosomal recessive manner, it is common for there to be no known family history of biotinidase deficiency. Third, arrange an immediate referral to a biotinidase deficiency specialist for a comprehensive clinical evaluation, discussion of a treatment plan, and genetic counseling. The specialist is typically a pediatric geneticist. The clinical evaluations should include a comprehensive physical assessment by an experienced biotinidase deficiency specialist. Fourth, working with the appropriate specialist, take steps to ensure biochemical and or molecular confirmation of the newborn screening result. Confirmatory testing includes biotinidase enzyme analysis, urine organic acid analysis, and BTD gene sequencing. Fifth, report the final diagnostic outcome back to your state newborn screening program. Biotinidase deficiency is highly treatable through biotin supplementation, and affected individuals can be expected to have normal physical and cognitive development with treatment. As you continue to care for your patient with a positive newborn screen for biotinidase deficiency, it is likely additional questions and concerns will come up. Here are some resources where you can obtain information on biotinidase deficiency, appropriate laboratories and tests, and genetic specialists. Before we end today's session, let's have a quick review. First, biotinidase deficiency is a serious condition, and identification of affected individuals is essential for the administration of early treatment. Second, newborn screening may identify both profound and partial biotinidase deficiency. Third, ACT sheets are freely available on the ACMG website to review in the event of a screen positive result. In addition to biotinidase deficiency, ACT sheets are available for many other conditions that can be identified through newborn screening.

newborn screening

biotinidase deficiency

genetic disorder

recycle biotin

primary care providers