In this issue: FasterCures investigates patient preferences in the development of new cancer screening technologies Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you! New Study Investigates Patient Preferences in the Development of Cancer Screening Technologies FasterCures, a center of the Milken Institute, works to build a system that is effective, efficient, and patient-centered with focus areas in accelerating innovation, building nonprofit capacity, improving the research and development environment, and strengthening global health. Additionally, FasterCures works to embed the experiences and preferences of patients across the biomedical ecosystem to address patient needs and improve outcomes. With this in mind, last fall, FasterCures published a study, The Impact of Insight: Patient Preferences in Novel Screening Technologies for Cancer, exploring patient preferences in cancer screening and early interventions with the goal of informing current patient care guidelines and the development of future cancer screening technologies and interventions. As a side note, our CEO Dr. Eszter Hars, had the privilege to participate in the latest cohort of the Milken Institute FasterCures LeadersLink Program and recently completed a capstone project centered around patient data resources. More about this project coming soon. What This Study Found As screening technologies advance and detect cancer earlier, it is imperative that the development process for early intervention modalities includes patient insights. The incorporation of patient preferences into the development and advancement of early intervention technologies and treatments are equally important. Based on their extensive research and engagement with stakeholders, this study identified the following patient preferences in cancer screening, early detection, and interventions: Image credit: The Impact of Insight: Patient Preferences in Novel Screening Technologies for Cancer This study also identified several key issues with the development of new cancer screening and early intervention modalities including: Unawareness of Individual Risk of Cancer and Recommended Screenings Lack of Diversity in Research Limited Access to Screening Tests Lack of Patient Engagement in the Development of Medical Products Limited Capabilities of Current Screening Tests To address these issues, the authors recommended multiple calls to action, encouraging patient insights to be actionably embedded throughout the research, development, and implementation of cancer screening and early intervention tools. Some of these calls to action include: Invest in research to better understand the biology of cancer, Stratify cancer screening recommendations based on genetic risk, lifestyle, and behavior, Increase the use of genetic testing to create personalized screening plans for individuals with a family history of cancer, Ensure clinical trials for new technologies include participants from diverse communities, Invest in accessible screening technologies and/or initial, self-administered screenings in the home, Continue to engage patients in the development of new screening technologies and early interventions for cancer treatment, and Prioritize the development of screening technologies for lethal cancers and cancers without current screenings. What Does This Mean for You? While we recognize there is more complexity to SDS than its cancer risk and developing and implementing appropriate cancer screening recommendations, this study serves as a great example of the unique needs and preferences that exist amongst different disease communities. SDS Alliance is committed to not only responding to these authors’ calls to action, but also to exploring and incorporating the needs and preferences of the SDS community when establishing our research priorities and designing clinical trials. Together, we can improve outcomes and find a cure for SDS! Make your voice heard: Engage, share your story, and get involved in advocacy. __________________________________________________________________________________ The Science Snapshot this week contains content modified from materials distributed by the Milken Institute and FasterCures. The Impact of Insight: Patient Preferences in Novel Screening Technologies for Cancer Milken Institute: FasterCures In Partnership With: The Rising Tide Foundation September 21, 2023 Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

In this issue: Data sharing with privacy protection. How can we work together to put together the SDS puzzle? Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you! The Importance of Data Collection and Data Privacy in Rare Disease Research Research in rare disease is comparable to putting together a puzzle with each piece of that puzzle serving as a small piece of information about a condition, or in our case, Shwachman-Diamond Syndrome (SDS). To understand the whole picture of SDS, develop treatments, and discover a cure, we need to gather all of the puzzle pieces. This gathering of information is what we call data collection. In the context of rare disease research, because of the scarcity of individuals affected, each piece of information or data point (i.e., every piece of the puzzle) becomes very valuable. And when we put the puzzle pieces together (a process known as data aggregation), it becomes easier to see the complete picture, or gain a better understanding of the disease landscape. This process of putting the puzzle together is crucial for advancing research in rare disease because with more information, scientists and researchers can learn more about the causes, symptoms, and potential treatments for these rare conditions. Image credit: https://www.zamplo.org/rare-disease However, the significance lies not only in the collection and synthesis of data but also in the collaborative sharing of this information and findings. If only one person had some puzzle pieces and kept them to themselves, we wouldn't be able to see the whole picture. Similarly, when researchers share their findings and data with each other, it helps everyone in the scientific community work together to solve the puzzle of rare diseases. In rare disease research, while collaboration is the key to advancing research in rare disease, data privacy and the protection of participants and their data is equally as important. To make a simple analogy, it's like having a lock on your diary or a secret box where you keep your special things. In the world of data collection, data privacy entails the responsible and secure handling of information. It is imperative to balance the necessity of sharing critical information with the imperative to protect individuals' private data. This ensures that progress in understanding and treating rare diseases is achieved while upholding the ethical responsibility researchers have to respect patient privacy. As we begin the new year, SDS Alliance wants to renew our commitment to the SDS community to support, fund, and perform research that is collaborative and productive, while also protecting the privacy of our patient community. We look forward to working together to assemble the puzzle that is SDS in 2024! __________________________________________________________________________________ For more information about data collection and data privacy in rare disease research, you can view this presentation by Sanath Kumar Ramesh, hosted by the Critical Path Institute’s Rare Disease Cures Accelerator-Data and Analytics Platform (RDCA-DAP), recently. __________________________________________________________________________________ Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

In this issue: What is a ribosome and how do Lego blocks relate to Shwachman-Diamond Syndrome? Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you! Decoding Ribosomes and Exploring Ribosomopathies through the Lens of Shwachman-Diamond Syndrome Within the complex machinery of our cells, ribosomes play a crucial role in crafting proteins – the building blocks essential for life and most of our bodily functions. In this blog post, we'll break down what ribosomes are and explore ribosomopathies, using Shwachman Diamond Syndrome (SDS), as an example of how issues with ribosomes can impact health. The Role of Ribosomes Ribosomes are cellular structures responsible for translating the genetic instructions encoded in our DNA into proteins. These microscopic protein factories assemble amino acids in a specific sequence to form proteins that carry out diverse tasks within our cells. Proteins are vital for cell structure, function, and regulation, making ribosomes pivotal in maintaining our overall health. (With how big of a role ribosomes play, it is not surprising that many organ systems in the body are affected if the process of protein production is disrupted!) The creative video below explains protein synthesis and the important role ribosomes play in this process! Understanding Ribosomopathies in the Setting of Shwachman-Diamond Syndrome Ribosomopathies are a group of rare genetic disorders characterized by abnormalities in the structure or function of ribosomes. These disruptions can lead to errors in protein production (i.e., synthesis), resulting in either the formation of defective proteins or a shortage of functional ones. The consequences of ribosomopathies can manifest in various health issues, affecting different organs and systems in the body. Another way to think about protein production is by comparing ribosomes to a pair of hands that use individual Legos (i.e., amino acids) to build large Lego towers (i.e., proteins). The order of amino acids, or Lego blocks, is specified by the genetic code in our DNA. In SDS, a genetic change in a patient’s DNA (i.e., a mutation) reduces the number of functional ribosomes, which in turn reduces the cells' ability to make enough protein overall. It’s like not having enough hands to meet the protein demands of the body. In SDS, the dysfunction of ribosomes impacts the bone marrow's ability to produce healthy blood cells. This can lead to conditions like anemia, where there's a deficiency of healthy red blood cells, affecting oxygen transport, resulting in fatigue and impacting overall well-being. The Path Forward SDS Alliance, researchers, and physicians are actively engaged in unraveling the complexities of ribosomopathies. For example, Drs. Venturi and Montanaro described How Altered Ribosome Production Can Cause or Contribute to Human Disease in their 2020 article published in Cells, which provides an overview of other ribosomopathies such as Diamond-Blackfan anemia and Treacher Collins syndrome. Additionally, Dr. Alan Warren's laboratory has published several manuscripts, Molecular basis of the human ribosomopathy Shwachman-Diamond syndrome (2018) and Defective ribosome assembly in Shwachman-Diamond syndrome (2011), which provide more information about the role of ribosomes in SDS. By studying conditions like SDS and other ribosomopathies, scientists aim to understand the molecular intricacies that lead to disruptions in ribosomal function. This deeper understanding holds the key to developing targeted therapies and interventions for individuals affected by these rare disorders, offering a brighter outlook for those facing the challenges of ribosomopathies. __________________________________________________________________________________ To learn more about the medical aspects of and science behind SDS, visit our What is SDS? and Science webpages. __________________________________________________________________________________ Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

In this issue: What does it mean to have a clinical diagnosis of SDS and who are some of the important care team members who can help? Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you! The Role of Multidisciplinary Care Teams in Establishing a Clinical Diagnosis of SDS Over the past few months in our Science Snapshot series, we have discussed the diagnostic odyssey for SDS from multiple perspectives including considerations for receiving a genetic diagnosis of SDS and the cost of a delayed diagnosis. In our Science Snapshot this week, highlighting this article published by researchers at the National Cancer Institute (NCI), we will be reviewing what it means to have a clinical diagnosis of SDS and how a multidisciplinary care team can be critical in making an SDS diagnosis. We have also touched on this topic last weekend at our "Ask an Expert" community chat, where our guest expert Ashley Thompson, board certified genetic coucelor and new team member at the SDS Alliance, presented on genetic testing and offered her insights. If you missed the live session, you will be able to catch up on the recording on our YouTube channel. (Coming soon. We will update the link below). What is a Clinical Diagnosis of SDS? Diagnosing SDS involves a comprehensive assessment of clinical features, genetic testing, and consideration of associated complications. Differentiating between clinical and genetic diagnoses is essential in understanding SDS. A clinical diagnosis relies on the identification of observable symptoms and features through physical examinations and medical history assessments. Clinical diagnosis of SDS are often made based on the presentation of hallmark symptoms of SDS, including exocrine pancreatic insufficiency, neutropenia, and skeletal. In contrast, a genetic diagnosis of SDS involves completing genetic testing to identify genetic mutations in a known SDS gene. While positive genetic testing can confirm a clinical diagnosis of SDS, it is important to recognize negative genetic testing does not rule-out a clinical diagnosis of SDS. Interestingly, approximately 10% of individuals with SDS actually have negative genetic testing. Research to discover new SDS genes is on-going. Individuals with a clinical suspicion for SDS and negative genetic testing should talk with their care team about what additional testing could be informative. Does clinical presentation of SDS correlate with genetic status? In a manuscript that was published last year, researchers at the NCI attempted to determine if there was a difference in clinical presentation of SDS based on an individual’s specific genetic variant (i.e, mutation) by analyzing the medical records of fifty-four participants with a clinical suspicion SDS in their Inherited Bone Marrow Failure Syndromes cohort. In Figure 1 from this article (as shown below), the authors presented the classification schema they used in establishing a clinical diagnosis of SDS versus an SDS-like clinical presentation. Individuals with both pancreatic insufficiency and neutropenia were considered to have a classical presentation of SDS. While the authors determined those with either pancreatic insufficiency or neutropenia in the presence of a hypocellular bone marrow constituted an SDS-like diagnosis. Contrary to their hypothesis, the findings of this study suggest there was no distinct clinical presentation associated with an individual’s specific genetic change (i.e., mutation). Overall, the authors reported a narrow genotypic spectrum in not only the SDS cohort at the NCI, but also in other cohorts based on a literature review - the c.258+2T>C and c.183_184TA>CT variants in SBDS were the most common genetic changes in those with SDS. The hallmark clinical features of SDS, including exocrine pancreatic insufficiency, neutropenia, and skeletal dysplasia, were observed consistently among patients with positive genetic testing regardless of the variant type (i.e., a common vs more rare variant in SBDS). Additionally, the study noted a higher prevalence of MDS and AML among pediatric SDS patients with an known genetic cause, indicating an increased risk of hematologic malignancies in this population. The rarity of solid malignancies, such as breast and ovarian cancer, was also highlighted. How a Multidisciplinary Care Team Can Help Establish an SDS Diagnosis This study emphasizes the need for a collaborative approach involving various specialties to streamline the diagnostic process, provide comprehensive care, and address potential complications, including an increased risk of hematologic malignancies in pediatric SDS patients. We have adapted Figure 4 from this article (see below) to provide a visual of the different providers and evaluations that can play an important role in establishing an SDS diagnosis. This collaborative approach to receiving an SDS diagnosis ensures a comprehensive evaluation of clinical features and facilitates the incorporation of genetic testing for confirmation. Early diagnosis facilitated by a multidisciplinary team can help ensure prompt initiation of appropriate treatment and management strategies for individuals with SDS. For more information regarding the clinical presentation of SDS and flyers about SDS to share with your care team, you can visit our “What is SDS?” page. Disclaimer: The information contained in this blog post is an overview of published research and is not intended to be medical advice. If you are concerned you, or a loved one, has SDS, please contact your healthcare team. Shwachman Diamond syndrome: narrow genotypic spectrum and variable clinical features. Thompson AS, Giri N, Gianferante DM, Jones K, Savage SA, Alter BP, McReynolds LJ. Pediatr Res. 2022 Dec;92(6):1671-1680. doi: 10.1038/s41390-022-02009-8. PMID: 35322185 Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

In this issue: Breaking news! First CRISPR-based therapy approved by the FDA for treatment of a genetic blood disorder - sickle cell disease - in humans. Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you! FDA approves first gene-editing treatment for human illness In a landmark decision, the Food and Drug Administration (FDA) approved the first gene-editing treatment based on the transformational new technology CRISPR to alleviate a human illness, namely sickle cell disease, which is a rare and severe blood disorder. You can now find countless news reports on the topic. To start, we suggest reading this great summary by NPR. What is CRISPR? The Broad Institute offers this concise explanation: CRISPR” (pronounced “crisper”) stands for Clustered Regularly Interspaced Short Palindromic Repeats, which are the hallmark of a bacterial defense system that forms the basis for CRISPR-Cas9 genome editing technology. In the field of genome engineering, the term “CRISPR” or “CRISPR-Cas9” is often used loosely to refer to the various CRISPR-Cas9 and -CPF1, (and other) systems that can be programmed to target specific stretches of genetic code and to edit DNA at precise locations, as well as for other purposes, such as for new diagnostic tools. With these systems, researchers can permanently modify genes in living cells and organisms and, in the future, may make it possible to correct mutations at precise locations in the human genome in order to treat genetic causes of disease. Our website highlights some great videos explaining the concept. Why does it matter to SDS? Like sickle cell disease, SDS is a genetic blood disorder. Both diseases can be treated by a stem cell (or bone marrow) transplant, but because of the high risk and the need for a suitable donor, a transplant is not in reach for many who need urgent treatment. That's where gene therapy comes in. The type of gene therapy highlighted here works by removing hematopoietic stem cells from the patient themselves, "fixing" the genetic problem, and then infusing the cells back into the patient. This process has several advantages over traditional stem cell transplants. 1. Patients don't depend on finding a matching donor, and 2. The risk of serious complications associated with an unrelated donor transplant (i.e., graft versus host disease GvHD) is reduced (or perhaps even eliminated). Patients still need to undergo arduous conditioning with chemotherapy to prepare the bone marrow to accept the new cells, but there have been significant advances in that area as well. Of course, there are new risks that have to be evaluated, such as the risk of off-target effects. Researchers have to show that the gene editing procedure only fixes the intended gene sequence and doesn't alter any other sequence that could inadvertently lead to increased cancer risk or other unintended consequences. In the case of the newly approved therapy for sickle cell disease, the researchers were able to demonstrate that the therapy is SAFE and effective. This matters for SDS in several ways. By going through the whole regulatory process of gaining FDA approval, researchers, drug developers, and the FDA now have more clarity on the regulatory pathway; There is now precedent on how to demonstate SAFETY. We believe this will greatly reduce the cost of developing this technology for other blood disorders, including SDS. Several labs around the world are working on developing CRISPR-based therapies for SDS. Many technical challenges have yet to be overcome, but this approval by the FDA gives us tremendous hope that this could someday become a reality for SDS patients, too. Check out the recording of our SDS POPS (Patient Advocacy and Partnering Summit) from last May for additional insights. More on this subject soon. Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

Huge SDS advocacy and awareness win: Osmosis video on Shwachman-Diamond Syndrome receives thousands of views, with millions more as a potential reach As part of the SDS Alliance's efforts to raise the profile of Shwachman-Diamond Syndrome as an important disease worthy of attention by the medical and research community, we devised a plan to reach the right audience in impactful ways. As such, the next generation of doctors is a major audience to engage. Therefore, we reached out to National Organization for Rare Disorders (NORD) and Osmosis.org earlier this year to propose the creation of a video dedicated to Shwachman-diamond Syndrome. Osmosis.org has the biggest reach into the community of future doctors and caring healthcare providers though their unique approach to education with high quality and medically reviewed videos and innovative learning platform. We are so excited and humbled to announce that an Osmosis.org has created a video on Shwachman-Diamond Syndrome, and published as part of the "Year of the Zebra" Initiative. For context, there are over 10K rare diseases, and so it is a huge deal for SDS to be featured among just a handful of zebras on this impactful platform. The video provides a comprehensive overview of SDS in just 5-minutes, in a concise, inviting, and easy to follow format. The impact is worth celebrating. In the first month alone since publishing, the video has been viewed over 4,000 times. Which means that over 4,000 more future doctors and healthcare providers are now aware of SDS and are more likely to consider testing patients for it and/or understand what specialists to consult. And this is just the start. Osmosis.org has over 6 million subscribers and surpassed 3 million subscribers of their YouTube channel, as of last month. An faster diagnosis and better care will be of real, tangible benefit for new patients and families, as well as research and therapy development efforts moving forward. We encourage the entire SDS community to spread the word and share the video widely and often. It's easy to do. Share this blog post using the sharing buttons on the bottom our page on What is SDS (with the Osmosis video embedded on top), or the YouTube link to the SDS video Our heartfelt THANK YOU to the Osmosis team for creating this amazing resource, and to the SDS community for their help spreading the word. It takes a village. We are turning hope into action, together. What is the "Year of the Zebra" initiative? 2023 is the 40th anniversary of the Orphan Drug Act which gave hope to the hundreds of millions of people around the world who are directly affected by rare disorders (also known as “zebras,” because they are less common than horses). Elsevier Health is launching an ambitious initiative called “The Year of the Zebra” to educate millions of current and future healthcare professionals, caregivers, researchers, patients, family members, and the general public about these zebras. What is Osmosis.org from Elsevier? Osmosis.org is a leading medical & health education platform with an audience of over 6 million current & future clinicians & caregivers. Their vision: Everyone who cares for someone will learn by Osmosis! Their YouTube channel features general consumer health videos to educate the public about important medical concepts. The Osmosis.org learning platform features more in-depth basic and clinical sciences videos for health professionals and students, hundreds of decision making trees, thousands of board-style practice questions and flashcards, and advanced features like quiz builders, playlists, collaborative tools, mobile app, and more. Watch this video introduction to learn more about the power of their approach. __________________________________________________________________________________ Do you enjoy the SDS Alliance Blog and SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

In this issue: The importance of knowing your family health history and how to have these delicate and powerful conversations Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you! Nurturing Health Through Generations: A Guide to Family Health History Month November is Family Health History Month — a time to begin to unravel the narrative that shapes our well-being. In this Science Snapshot, we’ll explore the significance of Family Health History Month and discuss how to approach these delicate, yet powerful conversations surrounding family health while visiting with loved ones during this holiday season. Understanding Family Health History: Family health history refers to a record of diseases and health conditions that run in your family. It's like a biological roadmap that can help provide insight into potential health detours we may encounter. By uncovering patterns of illnesses among close relatives, individuals can gain valuable insights into their genetic predispositions. Why Family Health History Matters: Predictive Power: Your family's health history can provide clues about your risk for certain conditions, such as heart disease, diabetes, or certain types of cancer. Understanding your family's health history allows you to grasp the genetic risk you inherit and can potentially pass on to future generations. Empowering Health Literacy: Understanding the familial and genetic underpinnings of health conditions fosters health literacy and empowers individuals to make informed decisions about their lifestyle choices, preventative screenings, and healthcare choices. Personalized Healthcare: Armed with knowledge about your family's health, you can work with healthcare providers such as your primary care physician and/or genetic counselor to create personalized healthcare plans. This proactive approach enables early detection and management of potential health risks. You can use tools such as My Family Health Portrait (more details at the bottom of this post) to keep track of your family health information and share it with your health care providers. Talking to Your Family: Approaching the topic of family health history can be sensitive, but it's a conversation worth having. Here are some tips on how to broach the subject: Create a Safe Space: Choose a setting that fosters open communication, free from distractions and time constraints. Express Empathy: Acknowledge that discussing health issues can be emotional. Approach the conversation with empathy and understanding. Lead by Example: Share your own health history first. This can help others feel more comfortable opening up about their own experiences. Use Open-Ended Questions: Instead of asking yes-or-no questions, use open-ended ones to encourage more detailed responses. For example, ask, "Can you tell me about any health conditions that run in our family?" Highlight the Benefits: Emphasize the positive impact of understanding family health history on everyone's well-being. Explain how it can guide healthier lifestyle choices and preventive measures. Family Health History Month serves as a reminder of the valuable information embedded in our family trees. Initiating conversations about health history within the family may initially feel daunting and uncomfortable, but the benefits can far outweigh any initial discomfort. The insights gained from family health conversations are invaluable, shaping a roadmap for a healthier future. Join us during our next Community Conversation on Sunday, December 10th to continue the conversation about genetics and how genetic testing for SDS can help your family! __________________________________________________________________________________ My Family Health Portrait, a tool from the Surgeon General, allow you to: Enter your family health history. Learn about your risk for conditions that can run in families. Print your family health history to share with family or your healthcare provider. Save your family health history so you can update it over time. __________________________________________________________________________________ For more information about Family Health History, you can visit these websites: CDC: Knowing is Not Enough—Act on Your Family Health History CDC: Family Health History and Cancer NIH: Family Health History for Patients and Families __________________________________________________________________________________ Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

In Loving Memory Here is Jason's story, as told by his mom Ginny. After an emergency C-section on April 4, 1977, Jason entered the world at about 6PM. At his second visit with the pediatrician, I was asked to bring him to the hospital because they didn’t like his blood tests. They suspected leukemia but nothing really showed up and they sent him home. For a few years he did relatively well except he kept getting the croup. Then when he was about 4 he became sick and couldn’t eat but kept having diarrhea. Eventually, he was admitted into the hospital. At that point he wasn’t eating or drinking so they gave him an IV and watched him because there were no fluids in his little body. After numerous hours watching him, he finally urinated. It was at that point that we were sent up to Children’s Hospital of Pennsylvania (CHOP). We spent several years at CHOP traveling back and forth, collecting his bowel movements, getting X-rays and having bone marrow tests. They thought he had Cystic Fibrosis and/or Crohn’s disease. After numerous hospital stays, numerous X-rays, etc., the radiologist came running after us to see the doctor Jason saw. She had just attended a conference about SDS and wanted to take yet another X-ray but this time of his knee and wrist. Sure enough he showed the signs she had heard about for SDS. This began even more visits until he was finally diagnosed. In the middle of all this I got divorced and moved back to NY with the boys to live in my parent’s house. Jason was seeing Dr. Jeff Lipton and he was amazing. We found out that Jason was in need of a bone marrow transplant and it turned out that my other son, Brad was a perfect match. He was going to be the first SDS patient in the world to receive a transplant. Well, the transplant was successful, however, the chemo he received killed his heart cells. Jason passed away on August 15, 1987. He was 10 years old. Ginny, Jason's mom, wrote a beautiful poem. I Am Still Their Mother Long before the child was born I dreamed of being a mother Into my life came a beautiful boy With a smile that made me melt He was tiny, soft and full of life And I cried when I first held him. As he grew he became part of me And we laughed and cried together. It seemed like I needed nothing more Till I found out he would have a brother. Along came this fabulous bruiser of a child And the three of us could do no wrong As long as we were together! But all that's perfect cannot last And my number one son left us all too soon. We cried, we talked, we tried to understand, But number two and I had to pull it together. And so we did and through us he lives And I am still their mother! Ginny Gordon Bennette

In Loving Memory Melissa passed away from complications after a stem cell transplant, necessitated by Shwachman-Diamond Syndrome. Her mother Sherry created a Facebook page (Swab4Melissa SDS Cancer Awareness) in her memory to advocate for various cancer awareness campaigns and to spread positivity through their #WeChoseJoyTogether campaign, which includes a balloon initiative inviting anyone in the community to bring smiley face Mylar balloons to their local children's hospital. Sherry shared her story in the context of grief through a beautiful video for the Stories of Hope series by the New Hope Grief Support Community. Thank you for sharing Melissa's and your family's story, Sherry.

In this issue: New study reports the economic impact of a delayed diagnosis is up to $517,000 in avoidable costs per patient in rare diseases Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you! Groundbreaking Study Reveals Staggering Economic Toll of Delayed Rare Disease Diagnosis: Report Calls for Urgent Advancements in Policies and Technologies In our Science Snapshot earlier this month, we discussed the diagnostic odyssey many individuals with Shwachman-Diamond Syndrome experience. Because these long diagnostic journeys are not uncommon across rare disease, there are organizations such as The EveryLife Foundation for Rare Diseases (and SDS Alliance!) who are committed to performing and funding research crucial to shortening this time to receive a diagnosis. In September, the EveryLife Foundation released one of the first studies of healthcare resource utilization and costs for patients with rare disease. The Cost of Delayed Diagnosis in Rare Disease: A Health Economic Study is a landmark report showing the cost savings of receiving a more timely diagnosis in rare disease. This study was performed as a follow-up to the National Economic Burden of Rare Disease Study and provides an in-depth analysis of the avoidable costs associated with seven rare diseases: Adrenoleukodystrophy (ALD), Duchenne muscular dystrophy (DMD), Fragile X syndrome (FXS), Generalized myasthenia gravis (gMG), Pompe disease, Severe combined immunodeficiency disorder (SCID), and Wilson disease. Although Shwachman-Diamond Syndrome was not included in the group of diseases focused on in this study, these results provide evidence to support federal and state policies expanding diagnosis and treatment options for all rare diseases. Importantly, the results from this study were presented on Capitol Hill during the Rare Disease Congressional Caucus Briefing in September. What This Study Found Some key findings from this report include: On average, it takes more than 6 years and nearly 17 doctor visits, hospitalizations, and other health-related trips, to receive a rare disease diagnosis after symptoms begin. The diagnostic odyssey costs individuals and families over $220,000, on average, in avoidable medical bills and lost income — and as high as $517,000 across the 7 diseases studied. There is immense value in timely diagnosis and newborn screening which improve outcomes, both medically and financially. Shortening the diagnostic odyssey saves money for individuals, caregivers, and the healthcare system, while improving health outcomes by providing earlier access to supportive therapies and treatment, delaying or preventing disease complications and physical disabilities, and reducing or eliminating costly and unnecessary services or procedures. Image credit: The Cost of Delayed Diagnosis in Rare Disease: A Health Economic Study Infographic What Can You Do? Make your voice heard: Engage, share your story, and get involved in advocacy. These findings demand attention from researchers, policy makers, healthcare providers, and employers. There is an urgent need to fund research, enhance awareness, and improve access to diagnosis, care, and treatment of rare disease. Contact your elected representatives, share the study findings, and urge Congress and state governments to enhance newborn screening and other policies that facilitate patient access to diagnosis and treatment. __________________________________________________________________________________ The Science Snapshot this week contains content modified from materials distributed by The EveryLife Foundation for Rare Diseases. The Cost of Delayed Diagnosis in Rare Disease: A Health Economic Study EveryLife Foundation for Rare Diseases In Partnership With: The Lewin Group, part of Optum Serve Expert Stakeholders The Rare Disease Community September 14, 2023 Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

In this issue: Two new publications by Dr. Seth Corey's group. One comparing genes associated with SDS-like syndrome, and the other on their recent work on zebrafish. Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email connect@SDSAlliance.org or message us on Facebook! This is all for you! New review article by Dr. Corey: Shwachman-Diamond syndromes: clinical, genetic, and biochemical insights from the rare variants The gene that causes SDS in over 90 of patients is the SBDS gene, but other genes have been associated with SDS or SDS-like syndromes as well. The experts have not yet agreed on whether these genes should be considered SDS causing, or rather causing similar but distinct SDS-like syndromes. Dr. Corey's review article is highlighting commonalities on the genes EFL1, DNAJC21, and SRP54 when it comes to symptoms and where they fit into the overall pathways of ribosome and protein maturation. BDS, EFL1, DNAJC21, and SRP54 encode proteins involved in ribosome assembly and nascent polypeptide synthesis. SDS has been viewed as a ribosomopathy. This term has been applied to diverse diseases with germline or somatic mutations, such as Treacher Collins syndrome, DiamondBlackfan anemia, cartilage hair hypoplasia, and del(5q) MDS. The authors "suggest using the term Shwachman-Diamond syndromes or Shwachman-Diamond-like syndrome to denote disorders that may involve blood and/or pancreatic abnormalities, and which result from germline variants that encode proteins affecting ribosome biogenesis and early protein synthesis. The term Diamond-Blackfan anemia should be reserved for those with congenital hypoplastic anemia." The full article is available free (open access): Shwachman-Diamond syndromes: clinical, genetic, and biochemical insights from the rare variants. Kawashima N, Oyarbide U, Cipolli M, Bezzerri V, Corey SJ. Haematologica. 2023 Oct 1;108(10):2594-2605. doi: 10.3324/haematol.2023.282949. PMID: 37226705 New publication by Dr. Corey's group: SBDSR126T rescues survival of sbds−/− zebrafish in a dose-dependent manner independently of Tp53 In this new article, the research team is using their zebrafish model in which the SBDS gene has been deleted. They re-introduce various amounts of functional SBDS protein using genetic tools. The results show that the more functional SBDS protein there is, the better the fish model develops and survives; and that this phenomenon is independent of Tp53. This figure shows a summary of the work. The bottom row are zebrafish embryos that don't have any or enough functional SBDS protein, and therefore cannot develop beyond the early embryo stage. The top row depicts zebrafish that has the normal amount of SBDS protein and therefore develops normally. The rows in the model summarize what happens when there is less than normal amount of SBDS protein or if p53 signaling is disrupted. The full article is available for free (open access). SBDSR126T rescues survival of sbds -/- zebrafish in a dose-dependent manner independently of Tp53. Oyarbide U, Shah AN, Staton M, Snyderman M, Sapra A, Calo E, Corey SJ. Life Sci Alliance. 2023 Oct 10;6(12):e202201856. doi: 10.26508/lsa.202201856. Print 2023 Dec. PMID: 37816584 Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

This September, we took to opportunity to introduce the Shwachman-Diamond Syndrome community at the Chan Zuckerberg Initiative (CZI) Science and Society Meeting in California with a poster presentation focused on the resources and opportunities the SDS community has to offer. We earned a spot at this invitation-only meeting by being an awardee of the CZI Rare-as-One program. The meeting featured incredible success stories of patient advocacy organization in pushing for cures and groundbreaking collaboration opportunities. We are incredibly grateful for being part of this community and the transformative resources the program has bestowed on the SDS community. This poster was created as part of the Scientific Community Engagement Fundamentals course by the Center for Scientific Collaboration and Community Engagement, which Dr. Eszter Hars had the great pleasure to participate in last summer. The poster highlights a variety of aspects of the community, such as Community Overview to describe the community and how the different stakeholder groups and categories interact with each other Community Management to describe how the current de facto community manager is fostering the community and making visible the skills that are at play Community Membership to describe various personas in the community, highlighting what needs we may want to serve Community Value generated through collaboration and why we are investing resources to do this work Community Participation to describe the type of interactions that are involved in various programming and activities, exploring further how a Community Champions program fits in, and highlights Community Programming and future opportunities. Would you like to learn more about this work? Let us know! We can schedule a community presentation and share more individually. About the CZI Science in Society 2023 Annual Meeting: We full-heartedly echo the sentiments shared by CZI: We’re leaving our annual Science in Society Meeting invigorated by the power of partnership and the pivotal role of patients driving scientific progress in rare disease. This meeting was an opportunity for researchers, patients and stakeholders to pool knowledge, forge collaborations and address challenges and opportunities in diagnosis, equity, and the development of treatments and cures. The expanding community dedicated to advancing our understanding of rare diseases is genuinely remarkable!