Epidemiological data on rare diseases in China are currently limited. The objective of this study was to provide a comprehensive understanding of the prevalence and incidence of rare diseases by systematically analyzing the available epidemiological data. We conducted a comprehensive search of English and Chinese databases, the Incidence and Prevalence Database, the Chinese Rare Disease Guideline, and the Taiwan Health Promotion Administration from 2010 to 2023. We identified the top diseases and regions based on epidemiological data and present the maximum, minimum, and median prevalence and incidence values in tables and forest plots. 1,264 prevalence and incidence data were retrieved from 277 studies, guidelines and official websites, covering 110 rare diseases (53.1%) and 32 regions (94.1%). In terms of geographical regions, incidence or prevalence data were available for 32 regions (94.1%), excluding Tibet Hui Autonomous Region and Macao Special Administrative Region. In terms of rate, 60 and 77 out of 207 diseases (29.0% and 37.2%) had available incidence and prevalence data, respectively. Eight diseases had an incidence rate equal to or greater than that of 1,000 patients per million. The present study provides a comprehensive epidemiological analysis and valuable insights into the prevalence and incidence of rare diseases in China. Our findings underscore the pressing need for sustained drug research and medical support for individuals and families impacted by rare diseases.

The objective was to conduct a comprehensive review of the morbidity and mortality observed in published patients with gastrointestinal defects and immunodeficiency syndrome-1 (GIDID1) related to TTC7A abnormalities. This included phenotypic, genotypic, and therapeutic aspects. Twenty-seven articles were included, which represented a total of 83 patients. Mortality was of 65.8% of the cases with a mean death at 11.8 months. The mortality rate was 197.1 per 1,000 patients-years, which is significantly higher than other enteropathy types caused by defects in epithelial trafficking and polarity (such as MOY5B, STX3, EPCAM, SPINT2, TTC37 and SKIV2L). Prematurity was also significant, with an average gestational age of 34.8 weeks. Antenatal signs were observed in 30 patients, including 14 cases of hydramnios. Three distinct phenotypic associations were identified: immune deficiency and multiple intestinal atresia without enteropathy (ID/MI), immune deficiency and enteropathy without atresia (ID/E), and immune deficiency with multiple intestinal atresia and enteropathy (ID/MIA/E). The mortality rates for these groups were 91.6%, 47.3% and 55.5%, respectively (p = 0.03), at earlier age of mortality for the ID/MIA phenotype and a later one for the ID/E phenotype. ELA syndrome (Enteropathy, Lymphopenia and Alopecia) was only observed in the ID/E group. Among the three genotypes (double variant Nonsense NS/NS, variant Missense/Nonsense MS/NS, double variant Missense MS/MS), NS/NS was significantly associated with the ID/MIA phenotype (77.8%), while MS/MS was associated with the ID/E phenotype (73.7%). Few therapies have been shown to be effective in treating enteropathy, particularly immunosuppressive therapies and hematopoietic stem cell transplants. The use of Leflunomide in one patient did not yield successful treatment outcomes. In conclusion, we confirm association between mortality and phenotype, which is itself linked to genotype.

With the development of clinical experience and technology, rare diseases (RDs) are gradually coming into the limelight. As they often lead to poor prognosis, it is urgent to promote the accuracy and rapidity of diagnosis and promote the development of therapeutic drugs. In recent years, with the rapid improvement of single-cell sequencing technology, the advantages of multi-omics combined application in diseases have been continuously explored. Single-cell metabolomics represents a powerful tool for advancing our understanding of rare diseases, particularly metabolic RDs, and transforming clinical practice. By unraveling the intricacies of cellular metabolism at a single-cell resolution, this innovative approach holds the potential to revolutionize diagnosis, treatment, and management strategies, ultimately improving outcomes for RDs patients. Continued research and technological advancements in single-cell metabolomics are essential for realizing its full potential in the field of RDs diagnosis and therapeutics. It is expected that single-cell metabolomics can be better applied to RDs research in the future, for the benefit of patients and society.

Gene therapy for monogenic auditory neuropathy (AN) has successfully improved hearing function in target gene-deficient mice. Accurate genetic diagnosis can not only clarify the etiology but also accurately locate the lesion site, providing a basis for gene therapy and guiding patient intervention and management strategies. In this study, we collected data from a family with a pair of sisters with prelingual deafness. According to their auditory tests, subject Ⅱ-1 was diagnosed with profound sensorineural hearing loss (SNHL), Ⅱ-2 was diagnosed with AN, Ⅰ-1 was diagnosed with high-frequency SNHL, and Ⅰ-2 had normal hearing. Using whole-exome sequencing (WES), one nonsense mutation, c.4030C>T (p.R1344X), and one missense mutation, c.5000C>A (p.A1667D), in the OTOF (NM_001287489.1) gene were identified in the two siblings. Their parents were heterozygous carriers of c.5000C>A (father) and c.4030C>T (mother). We hypothesized that c.5000C>A is a novel pathogenic mutation. Thus, subject Ⅱ-1 should also be diagnosed with AN caused by OTOF mutations. These findings not only expand the OTOF gene mutation spectrum for AN but also indicate that WES is an effective approach for accurately diagnosing AN.

Rheumatoid arthritis (RA) is an autoimmune disease with complex etiology, and its pathological mechanism remains unclear. Our aim was to explore the effect of protein succinylation on RA by silencing Sirt5, sequencing succinylated proteins, and analyzing the sequencing results to identify potential biomarkers. We wanted to gain a clearer understanding of RA pathogenesis, quantitative assessment of succinylated proteins in Fibroblast-like synoviocytes (FLS) from RA patients using liquid chromatography- tandem mass spectrometry and enrichment analysis investigated using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). A total of 679 proteins and 2,471 lysine succinylation sites were found in RA patients, and 436 differentially expressed proteins and 1,548 differentially expressed succinylation sites were identified. Among them, 48 succinylation sites were upregulated in 38 proteins and 144 succinylation sites were downregulated in 82 proteins. Bioinformatics showed that succinylated proteins were significantly enriched in amino and fatty acid metabolisms. Results indicated that Sirt5 can affect various biological processes involved in RA FLSs, and succinylation caused by silencing Sirt5 plays a major role in RA progression. This study provides further understanding of RA pathogenesis and may facilitate searching for potential RA biomarkers.

Capitalizing on breakthroughs in reproductive genetics, the utilization of in vitro embryo culture and stem cell technologies heralds a transformative era in addressing global challenges posed by rare genetic diseases. These cutting-edge practices illuminate the intricacies of early human development, elucidate the mechanisms behind rare diseases, and guide the development of potential therapies. Balancing this remarkable innovation with necessary ethical considerations, these technologies have the potential to revolutionize the trajectory of rare genetic disorders, transforming the landscape of diagnosis, treatment, and genetic counseling while offering renewed hope for affected individuals and families worldwide.

We conducted a cross-sectional study to describe the health care problems of children with Down syndrome in Central Java, Indonesia. A total of 162 children (81 boys, 81 girls) with Down syndrome were included. Congenital heart defects and hypothyroidism were found in about 50%, followed by vision and hearing problems in 27.7% and 17.3%, respectively. Almost half of cases were diagnosed after the first month of age. Advanced maternal age was identified in more than 50%, and less than 10% was based on karyotype analysis. This study describes the essential issues such as critical co-morbidities, delayed diagnosis, advanced maternal age, and lack of (accessibility to) genetic testing facilities; thus, better health care and management is needed.

In Malaysia, rare diseases affect fewer than 1 in 4,000 people. As of 2020, 491 rare diseases have been recorded in Malaysia, but with limited epidemiological data. As the first study in Malaysia, this retrospective cohort study examined the epidemiology and admission-related healthcare costs for adult rare disease patients in Langkawi. Among the 38 patients, rheumatological rare diseases topped the list (39.5%). The annual admission rate for rare diseases was 0.9%. Langkawi patients had lengthy hospital stays (9.7 days) and a 7.9% mortality rate. 23.7% of patients defaulted to follow-up, and 7.9% were referred to a tertiary hospital due to inadequate equipment or speciality care. Admission costs were Malaysian Ringgits (MYR) 244,598.63 (~US Dollars (USD) 51,280), with 80.2% from medication. The average healthcare resource utilisation was MYR 6,436.81/patient/year (~USD 1,350/patient/year).

The Japanese Research Group for Neuro-infectious Diseases was founded in August 1996, and by 2004 it had evolved into the Japanese Society for Neuro-infectious Diseases. The Society focuses on neuroinfectious conditions (e.g., encephalitis/encephalopathy, myelitis, and meningitis), providing a venue for academic presentations and exchanges. Clinical guidelines for major neurological infectious diseases are also published by the Society, in order to meet the social demands of each era. Although the threat of herpes simplex encephalitis has declined due to acyclovir's introduction, the frequency of encephalitis or peripheral neuropathy caused by varicella-zoster virus is increasing. In Japan, prion disease, human T-cell leukemia virus-1 (HTLV-1)-associated myelopathy (HAM), subacute sclerosing panencephalitis (SSPE), and progressive multifocal leukoencephalopathy (PML) are designated as intractable diseases. The incidence of prion disease is 1.8/1,000,000 individuals, with the sporadic type accounting for 80%. Prion disease is fatal, and effective medications are awaited. HAM's prevalence is ~3/100,000 individuals, with a male-to-female ratio of 1:2–3. HAM is common in western Japan, including Kyushu and Okinawa. The prevalence of PML is rising with the spread of both immunosuppressive therapy for transplantation and treatment for multiple sclerosis. From late 2019 through 2020, the world faced a global outbreak of coronavirus disease 2019 (COVID-19) due to virus mutations, and the threat of new mutations persists. Close attention should be paid to the emergence of new neurological infections that could arise from abnormal weather patterns and/or a decline in immune function due to aging.