The Impact of COVID-19 on MPS
Heather Lau, MD

The COVID-19 global pandemic has made 2020 a year like no other. In her keynote presentation, Dr. Heather Lau delivers an overview of the disease, some recent U.S. statistics, and the varying ways it can impact the MPS community. The most common symptoms of COVID-19 have been fever, dry cough, and fatigue. Additional symptoms, including loss of smell, loss of taste, and skin rashes can develop prior to the dry cough and fever. Non-verbal children are likely to show increased irritability and behavioral changes. A condition called multi-systemic inflammatory syndrome in children (MIS-C), where different body parts and organs can become inflamed, may show up days or weeks after other COVID-19 symptoms have come and gone.

There are currently no proven treatments for COVID-19, but nine U.S. developers are currently working on vaccines. In the meantime, masks, social distancing, and other mitigation strategies need to continue. Managing MPS during the pandemic brings added challenges. While therapies were initially put on hold, they are now moving forward with new home-based options and pre-therapy quarantining protocols. Most recently, the return to school has presented a new set of challenges. Parents must consider the increased risk of spread among children and family members with in-person learning. Concerns with remote learning include a lack of engagement and socialization, leading to a potential increase in behavioral problems.

General MPS Overview and Clinical Trial Updates During a Pandemic
Joseph Muenzer, MD, PhD

Dr. Joseph Muenzer presented a general overview of Mucopolysaccharidosis (MPS) and Mucolipidosis (ML). MPS consists of a group of rare genetic disorders due to the deficiency of specific enzymes required for the breakdown of glycosaminoglycans (GAGS, formerly called mucopolysaccharides) in lysosomes. ML is a lysosomal storage disorder due to the deficiency of N-acetylglucosamine-1-phosphotransferase. Today, it is reported that the aggregate disease incidence is 1:25,000 and the diseases are classified as rare. Like all lysosomal diseases, Dr. Muenzer emphasized MPS and ML are progressive and have multisystemic involvement. “The hallmark of MPS diseases is the tissue storage of the glycosaminoglycans that results in the progression of these diseases.”, said Dr. Muenzer. He noted there is a wide clinical variation among the diseases and manifestations can include intellectual defect, short stature, severe bone disease, respiratory disease, joint stiffness, and shortened lifespan.

Dr. Muenzer explained that MPS and ML patients suffer from an enzyme deficiency and presented an excellent overview of enzymes, glycosaminoglycans, understanding of normal functioning cell structure. Enzymes are biological catalysts, like a piece of machinery, whose job is to break down GAGS in the body and prevent cellular storage build-up. If this breakdown does not occur because of the missing enzyme, accumulation of GAGS occurs. It is presented that the consensus among physicians and researchers is that the accumulation of GAGS in MPS is occurring much sooner than originally understood. While each disorder has a wide range of clinical involvement and severity, prediction of severity is limited. Currently, there are two primary treatment options for MPS – hematopoietic stem cell transplantation (HSCT) and IV enzyme replacement therapy (ERT). ERT is currently available for all MPS types except MPS III (Sanfilippo), due to its inability to cross the blood-brain barrier. However, three new treatment strategies are starting to show promise for Central Nervous System (CNS) disease – intrathecal ERT, gene therapy, and blood-brain barrier penetration of proteins. Currently there is research and clinical trials underway for MPS IIIA.

Newborn Screening: What is It? How Will It Help the Diagnostic Journey?
Barbara Burton, MD

Dr. Barbara Burton delivered an overview of the newborn screening (NBS) process, what it is, how states decide which diseases to screen for, and the status of newborn screening for MPS diseases. There is a federal Recommended Uniform Screening Panel (RUSP) that currently mandates NBS for 35 disorders. These are recommended for each state, but the states make their own decisions on which conditions will be screened. MPS I is has RUSP inclusion and the National MPS Society submitted a nomination for MPS II, Hunter Syndrome, earlier this year. MPS disorders are ideal candidates for NBS because of the rarity and severity of the conditions, the challenging diagnostic odyssey, and the major benefits to early detection with treatments available.

Testing has considerations as well. A positive screen does not necessarily mean a baby has MPS I. There can be false positives and further tests are needed. A carrier could produce a positive test. Also, a condition known as pseudodeficiency could develop a positive test. Pseudodeficiency is also more common than true deficiency in both the MPS I and MPS II testing. Screening could be done for all the MPS disorders – the technology exists, but there are other funding obstacles. Families are encouraged to be powerful advocates for implementing NBS conversations and testing at their state level. This can be achieved by attending advisory meetings, contacting legislators, and talking with the National MPS Society.