[Disease Awareness] Rare Diseases Affect Over 300 Million People!?

Hello everyone! Welcome to the AHI official account. Today, we will dive into the topic of "rare diseases" and gradually uncover the mysteries behind these conditions through the advanced research teams at Montefiore Medical Center and Albert Einstein College of Medicine.

Overview of Rare Diseases

Rare diseases refer to conditions that affect a small number of people. Though they may seem distant, there are over 10,000 known rare diseases, affecting more than 300 million people worldwide. These individuals are often overlooked and marginalized, especially in low- and middle-income countries. About 80% of rare diseases have genetic causes, nearly 70% manifest during childhood, and approximately 95% of rare diseases lack approved treatments. The average time to an accurate diagnosis is 4.8 years, and around 30% of children with rare diseases die before the age of five. From genetic disorders to complex metabolic abnormalities, the diversity of rare diseases makes diagnosis and treatment extremely challenging.

Disease Mechanisms: A Mysterious Biological Puzzle

Rare diseases often result from genetic mutations, which act like misplaced pieces in the body’s biological puzzle, leading to dysfunction in one or multiple systems. For example, a protein called fibrinogen may fail to form blood clots properly due to a genetic error, resulting in bleeding disorders. The U.S. National Institutes of Health estimates that there are as many as 10,000 rare diseases, but only a few are well-understood, with even fewer having known treatments. While many rare diseases affect only a small number of people, together they represent a significant unmet medical need affecting over 300 million people globally.

Diagnosis: The Power of Technology

In recent years, the precision and speed of genetic sequencing technology have greatly improved, while testing costs have significantly decreased, revolutionizing rare disease research. Whole-exome sequencing (WES) and whole-genome sequencing (WGS) have become common testing methods. Although these technologies can confirm known diseases, they may also reveal new rare or ultra-rare diseases. However, understanding these diseases caused by rare genetic variants remains a long-term challenge.

To address these challenges, the Rose F. Kennedy Intellectual and Developmental Disabilities Research Center (RFK IDDRC) at Einstein has implemented a multidisciplinary team approach known as the “IDD Gene Team Initiative.” This program aims to advance the understanding and treatment of rare genetic brain diseases. It brings together families affected by rare genetic disorders, clinicians, basic scientists, and trainees to collaboratively explore disease mechanisms and potential treatments.

During team meetings, family members share the child’s medical history and personal experiences, doctors discuss the clinical outcomes of the disease, and scientists provide biological insights into the relevant genes and, when possible, explore potential treatments. The medical team not only focuses on treating the disease but also works to improve the patient’s quality of life. For instance, for a rare metabolic disease, the medical team developed specialized dietary and medication plans to help the patient manage symptoms effectively.

Case Studies

SLC17A5 (Salla Disease)In 2017, the first IDD Gene Team meeting for SLC17A5 was held. The team included a 3-year-old boy, his parents, a geneticist from Montefiore, two neuroscientists from Einstein, and a leader from the RFK IDDRC. The parents shared their child’s experiences, and the scientists explained the two diseases associated with the SLC17A5 gene: Salla disease and Infantile Sialic Acid Storage Disease (ISSD). The parents of the SLC17A5 patient established the STAR Foundation (https://www.sallaresearch.org) in 2018, which now has its own scientific advisory board, including two Einstein faculty members who are part of the IDD Gene Team.

DYNC1H1In 2018, the first IDD Gene Team meeting for DYNC1H1 was held. The attendees included an 11-year-old boy and his parents, the leadership of the IDDRC, the child’s geneticist, two scientists (one focused on dynein and its function, the other on modeling brain disease), and a medical student interested in the disease. The parents shared their long diagnostic journey, eventually learning in 2018 that their son had a de novo pathogenic variant in the DYNC1H1 gene. The scientists explained how mutations in this gene lead to complex disease outcomes, such as Charcot-Marie-Tooth disease type 2 (CMT2), spinal muscular atrophy with lower extremity dominance (SMA-LED), malformations of cortical development (MCD), and severe intellectual disability.

PPM1D (Jansen de Vries Syndrome)In 2017, the IDD Gene Team meeting for PPM1D included a patient, his parents, a geneticist from Montefiore, a scientist specializing in iPSC/organoid modeling, and RFK IDDRC leadership. The family discussed the child’s early behaviors, including ADHD, auditory hypersensitivity, and sensory processing issues. The diagnosis was confirmed via WES as a de novo pathogenic PPM1D mutation. The scientists discussed the clinical consequences of this mutation and explored how iPSC methods could be used to further study the disease.

KDM5C (Claes-Jensen Syndrome, X-linked Intellectual Disability)The KDM5C story is one of the most compelling, gathering over a dozen affected families who first met at Einstein’s Rare Disease Day in 2020. A mother who established the STAR Foundation shared her experience of founding the organization. Two years later, the KDM5C Advocacy, Research, Education, and Support (KARES) Foundation (https://kares.foundation) was born. These gene team meetings fostered cooperation between families and medical experts, aiding understanding and support for KDM5C-related intellectual disabilities.

The Impact on Physicians, Scientists, and Trainees

The experience of the IDD Gene Team not only impacts the families involved but also deeply influences the doctors and scientists who work with them. Exploring the complexity of a rare disease enhances medical professionals' understanding of similar cases, broadening their expertise. Scientists and their trainees, who are often disconnected from real-life experiences, gain invaluable insights when seeing the direct impact of their research on patients’ lives.

The Importance of Rare Disease Research

Research on rare diseases provides a window into new molecular and cellular processes, offering new insights into normal physiology and more common diseases. For example, the study of genetic mutations in rare diseases has revealed new cellular pathways, which may be related to the pathogenesis of common diseases. By studying rare diseases, new therapeutic targets and strategies can be discovered, benefiting not only rare disease patients but also the broader medical community.

Thank you for reading! We hope you will continue following us to learn more about breakthroughs and innovations at Montefiore Medical Center in disease treatment. Remember to share and like this post to raise awareness about rare diseases. See you again!

We look forward to your continued attention!