Since its establishment in 2016, the National Rare Diseases Registry System of China (NRDRS) has accumulated valuable case data and bio-specimen for basic and clinical research on rare diseases in China. However, the emerging challenges in clinical diagnosis and treatment of rare diseases make it unable for data and resource platform to fully meet the diversified needs. Under this backdrop, we have developed a protocol to optimize and upgrade the system based on the core functions of the NRDRS platform. The goal is to leverage intelligent digital technologies to transform NRDRS into a new platform integrating multimodal data and auxiliary diagnostic and treatment functions. It is specified as the development and construction of "one platform and four intelligent tools." Currently, we have upgraded and developed NRDRS platform, intelligent tool for genotype-phenotype analysis of rare diseases, AI-assisted diagnostic tool for rare diseases, remote multidisciplinary diagnosis and teaching tool for rare diseases, drug screening and validation tool for rare diseases. The next step will focus on the promotion of the application of these tools in clinical settings in order to address the issue of severe imbalance in the allocation of resources for the diagnosis and treatment of rare diseases. This article provides an overview of the digital and intelligent upgrades of the NRDRS, the trials in applications in clinical settings, and direction in the future.

A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

Schimke immuno-osseous dysplasia (SIOD)caused by SMARCAL1 gene mutations is a rare genetic disorder characterized by multi-system involvement, including T-cell dysfunction, skeletal dysplasia, disproportionate short stature, nephrotic syndrome, and kidney failure. This multidisciplinary consultation involved a 9-year-old boy with intrauterine growth retardation, presenting with short stature, T-cell lymphopenia, proteinuria, and degenerative bone and joint disease. Treatment primarily focused on symptomatic and supportive care. Through the multidisciplinary rare disease consultation, holistic support was provided to the patient, offering comprehensive care from various specialtiesx.We also aim to use this case report to enhance clinicians′ under-standing of SIOD and improve the management and treatment of rare diseases.

Objective: To analyze the prevalence and trend of screening myopia among primary and middle school students in Linfen Community of Shanghai from 2019 to 2023, so as to provide a reference for the prevention and control of myopia from the perspective of the community. Methods: From 2019 to 2023, all primary(5) and middle(2) school students aged 6-15 years in Linfen Community of Shanghai were screened. Statistical analysis was performed using the Chi square test and trend Chi square test. The curve fitting model was used to fit the model of the increase rate of screening myopia among primary and middle school students in 2019, 2021 and 2023. Results: The overall rate of screening myopia among primary and middle school students in Linfen community from 2019 to 2023 was 55.17%. The prevalence rate of screening myopia was 79.43% in boys and 81.92% in girls in middle school, and the difference was statistically significant ( χ 2=5.71, P =0.02). In 2019, 2021, and 2023, the peak age of screening myopia among primary and middle school students in Linfen Community gradually occurred earlier, at the age of 7(12.13%), 6( 12.28 %), and 6(14.99%) years old, respectively. The growth rate of screening myopia in students aged 8-12 years in 2023 was lower than that in 2019 and 2021. Conclusions The screening myopia rate of primary and middle school students aged 6-15 years in Linfen Community is relatively high, with primary school girls higher than boys, and growth spurt accelerates. It is suggested that prevention and control of myopia in the community should focus on preschool children and adolescent girls.

As an important category of rare diseases, rare genetic kidney diseases have many types. In recent years, their diagnosis, treatment, research and management strategies have made great progress. Continuously more new genes and mechanisms have been discovered, giving rise to new technologies and drugs for precision medicine and clinical applications. This article systematically analyzes rare diseases involving the urinary system listed in the catalog of rare diseases in China, gives examples to illustrate the research and management methods for the diagnosis and treatment of rare genetic kidney diseases, promotes clinical applications of new drugs by expanding physiological mechanisms, introduces the application of special blood purification in the field of critical rare diseases, and provides an outlook forward to the future prospects of precise diagnosis and treatment of rare kidney diseases in China.

Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.

In recent years,with the development of gene testing and new drug research,the diagnosis and treatment of inherited diseases have made rapid progress,corresponding to higher requirements for genetics education.As a teacher of medical genetics,the author joined the course remodeling during last 10 years from a web-based study of genetic disorders to a"case-based learning"supported by flipped classroom in order to optimize teaching effects and learning outcomes.The result of this remodeling project proposes a new strategy to guide perspectives course de-sign in future.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disease caused by abnormal expression of glycosylphosphatidylinositol (GPI) on the cell membrane due to mutations in the phosphatidylinositol glycan class A(PIGA) gene. It is commonly characterized by intravascular hemolysis, repeated thrombosis, and bone marrow failure, as well as multiple systemic involvement symptoms such as renal dysfunction, pulmonary hypertension, swallowing difficulties, chest pain, abdominal pain, and erectile dysfunction. Due to the rarity of PNH and its strong heterogeneity in clinical manifestations, multidisciplinary collaboration is often required for diagnosis and treatment. Peking Union Medical College Hospital, relying on the rare disease diagnosis and treatment platform, has invited multidisciplinary clinical experts to form a unified opinion on the diagnosis and treatment of PNH, and formulated the Expert Consensus of Multidisciplinary Diagnosis and Treatment for Paroxysmal Nocturnal Hemoglobinuria (2024), with the hope of promoting the standardization of PNH diagnosis and treatment.

Background In recent years,rare diseases have become a major public health issue.There is an urgent need to improve the diagnosis and treatment for these diseases,and the training for doctors engaged in rare diseases is an important part of it.Methods This study conducted a questionnaire survey on the doctors engaged in rare diseases in Peking Union Medical College Hospital to better understand their characteristics and evaluate their psychological and working status.Results A total of 95 questionnaires from doctors engaged in rare diseases were collected in this study,among which the female:male ratio was 1.6∶1,and 63.2％of them were in the 40-54 age group.Their main reason for choosing rare diseases was the enjoyment in the process of studying rare diseases(64.2％).Compared with the 108 doctors not engaged in rare diseases surveyed during the same period,those working on rare diseases reported higher patient recognition based on self-evaluation(P＜0.001).In terms of the time-consuming work,in addition to routine medical work,teaching and research,34.7％of doctors engaged in rare diseases chose doctor-patient communication and 31.6％chose medical man-agement communication.Conclusions This study proposes some suggestions on the talent training for rare dis-eases,the establishment of continuing education platforms,and the technology and policy support needed through the analysis of the questionnaire survey results of doctors engaged in rare diseases.

Postsurgical hypoparathyroidism is a common cause of hypoparathyroidism, with a variety of clinical manifestations. It is life-threatening in acute and severe cases, and may lead to poor quality of life in chronic patients. It is imperative to consistently enhance the identification and governance of such circumstance. Focusing on the pathophysiological changes, clinical and biochemical features, acute and chronic treatments of postsurgical hypoparathyroidism, a consensus was developed by domestic experts from surgery, endocrinology and nephrology.