Welcome to the ACMG Knowledge Nugget on newborn screening for mucopolysaccharidosis type two or MPS two. 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 CMEs 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 MPS two ACT sheet, which is freely available@www.acmg.net slash a. CT 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 is 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. The session will cover background information on MPS two, including clinical features and the underlying genetic cause. Actions a primary care provider needs to take upon receiving a screen positive test result for mps two, clinical considerations and supplemental resources. MPS two also known as Hunter syndrome, is an X-linked lysosomal disorder caused by pathogenic variants found in the I D S gene. This leads to a decrease in ID ate two sulfatase or I two s enzyme activity. This change results in the accumulation of glycosaminoglycans or gags in the body's lysosomes. The accumulation of gags causes cellular dysfunction leading to enlarged tissues and organs. The presentation of MPS two is clinically variable and is usually classified into two main types, the attenuated or non neuropathic type and the severe or neuropathic type. However, it is important to note that there are overlapping symptoms between the two types, suggesting that the disease spectrum of MPS two is quite broad after diagnosis, it may be difficult to predict the type of MPS two and individual will have. Individuals with MPS two are usually asymptomatic until about age two to four, though some may initially present with an umbilical or inguinal hernia. A distinguishing and early feature of MPS two are hypopigmented, papules and nodules. Later symptoms may include slowed growth, coarse facial features, decreased joint mobility and abnormal bone growth with skeletal abnormalities. Individuals with severe MPS two often also exhibit developmental delays, CNS involvement in a more rapid progression of the disorder. MPS two is inherited in an X-linked manner. The X-linked inheritance of MPS two means that biologic males are more severely and more commonly affected than biologic females. At this time. Not all states provide newborn screening. For MPS two, 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 MPS two. Testing is mostly accomplished by examining levels of the ID urate two sulfatase or I two s enzyme, which is decreased in individuals with MPS two. Some programs also examine the level of gigs as a second tier test to help improve screening and rule out cases of pseudo deficiency. Pseudo deficiency is commonly seen in lysosomal disorders and is caused by certain known variants in the I D S gene. Pseudo deficiency means that a baby's I two s enzyme levels appear low upon testing, but this decreased activity does not cause disease. Babies with MPS two pseudo deficiency will have normal gag levels. These infants do not have and will never develop MPS two. Now that you have an understanding of what MPS two is, let's talk about what to do if you have a patient screen positive for MPS two during newborn screening, you'll 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, though some infants may have an umbilical or inguinal hernia. Provide the family with basic information about mps two. Second, take a family history with a particular focus on the potential signs and symptoms in young male siblings. Third, arrange a referral to an MPS two specialist for genetic counseling, 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 MPS two specialist. Fourth, working with the appropriate specialist takes steps to ensure biochemical and or molecular confirmation of the newborn screening result. Confirmatory testing includes I two s enzyme analysis, gag analysis, and I D S gene analysis. Fifth, report the final diagnostic outcome back to your state newborn screening program. Current treatment options for MPS two include hematopoietic stem cell transplantation and enzyme replacement therapy. As you continue to care for your patient with a positive newborn screen for MPS two, it is likely additional questions and concerns will come up. Here are some resources where you can obtain information on mps two appropriate laboratories and tests and genetic specialists. Before we end today's session, let's have a quick review. First, MPS two is a serious condition. An identification of affected individuals is essential for administration of early treatment. Second, newborn screening may identify both the severe or neuropathic as well as the attenuated or non neuropathic forms of mps. Two third ACT sheets are available on the acmg website to review in the event of a screen positive result. In addition to mps two ACT sheets are available for many other conditions

newborn screening

MPS two

Hunter syndrome

lysosomal disorder

genetic counseling