Traditional Chinese medicine (TCM) has increasingly attracted the attention of researchers as a potential complementary or supportive approach for selected rare diseases, but the characteristics and evidentiary strength of this literature remain unclear. This Correspondence summarizes publication patterns identified for the 121 conditions in the First Chinese Rare Disease List using Chinese and English sources searched from database inception through June 30, 2021. Fifty-five rare diseases were identified in 3,030 TCM-related publications, though the ten most frequently studied conditions accounted for more than 80% of the literature. Generalized myasthenia gravis, idiopathic pulmonary fibrosis, and multiple sclerosis together accounted for nearly half of all publications. Clinical studies and case reports or experience summaries predominated, whereas experimental studies represented only 9.03%. Oral herbal formulas were the most frequently reported intervention, and more than 95% of publications originated from mainland China. These patterns indicate growing interest but a fragmented, geographically concentrated, and methodologically limited evidence base; publication volume should not be interpreted as evidence of efficacy or safety. Future research should prioritize mechanistic studies, standardized and innovative clinical designs, rigorous safety and quality-control procedures, real-world evidence, patient-centered outcomes, and international collaboration to clarify the potential roles and limitations of TCM in rare disease management.

Japan's designated intractable disease (nanbyo) framework combines a population threshold with unresolved pathogenesis or treatment, long-term care needs, objective diagnostic criteria, and severity-linked assistance with medical expenses. We conducted a targeted narrative review of official Japanese sources and biomedical literature through August 3, 2026. Evidence ranged from regulatory approvals and randomized trials to observational, case-report, and preclinical data, so therapeutic maturity was assessed separately from mechanistic plausibility. We distinguished the 12 official skin/connective-tissue entries from six purposively selected designated entries or disease groups with decisive cutaneous phenotypes or Japan-specific translational value. The resulting 18-entry framework is illustrative, not exhaustive. It highlights Japan-specific biology or evidence regarding xeroderma pigmentosum, acquired idiopathic generalized anhidrosis, DPP-4 inhibitor-related bullous pemphigoid, generalized pustular psoriasis, cold-medicine-related SJS/TEN, anti-MDA5 dermatomyositis, and Nakajo-Nishimura syndrome. Recently approved indications or uses include dupilumab for adult bullous pemphigoid, IL-36 receptor blockade, topical COL7A1 gene delivery, autologous gene-corrected epidermal sheets, MEK inhibition, IL-1 blockade, and topical mTOR inhibition; JAK-interferon strategies remain investigational. We contend that Japan's designation infrastructure could become an interoperable translational platform linking natural-history cohorts, endotype-defined enrollment, mechanism-aligned endpoints, and multinational adaptive trials.

Fragile X syndrome (FXS) is the most common genetic cause of inherited intellectual disabilities. Individuals with full mutation of FXS exhibit physical and behavioral symptoms in addition to other comorbidities. The clinical features of FXS have been widely studied in Caucasians; however, they remain limited in the Asian population. This study aimed to characterize the spectrum and variability of physical and behavioral phenotypes in Asian populations. A total of 5,830 studies from the PubMed, ScienceDirect, Scopus, and Cochrane/CENTRAL databases were screened using the Covidence software. We identified FXS-specific research studies conducted in Asia that reported the clinical characteristics of individuals with FXS. This review summarizes 51 studies from different Asian regions. The frequently reported physical characteristics were large and prominent ears (72.63%), an elongated face (57.49%), and macroorchidism (45.21%). The three most prevalent behavioral characteristics were intellectual disability (ID), hyperactivity, and social withdrawal, reported in 99%, 77%, and 55% of all cases, respectively. Our findings show that the physical characteristics of FXS are variable in the Asian group but similar to those in other populations and are not recommended for early recognition. Individuals with intellectual disabilities, especially when combined with autism spectrum disorders and large prominent ears, are suggestive of further genetic testing for FXS.

Joubert syndrome (JS) is a rare ciliopathy characterized by neurological and multisystem manifestations; however, skeletal involvement remains poorly recognized. We report two genetically confirmed pediatric patients with JS illustrating different degrees of bone impairment. The first patient, a 2.5-year-old boy with a TMEM67 mutation, presented with severe hypotonia, profound immobility, multiple fractures, and markedly reduced bone mineral density (DXA Z-score −5.875), fulfilling the criteria for secondary osteoporosis and requiring bisphosphonate therapy. The second patient, a 5-year-old girl with an OFD1 mosaic mutation, showed delayed motor development and reduced bone mineral density (DXA Z-score −2.2) without fractures and was managed conservatively. These cases demonstrate the broad spectrum of skeletal manifestations in JS, ranging from low bone mineral density to severe secondary osteoporosis. Reduced mobility and chronic hypotonia may contribute to impaired bone mineralization. Increased awareness and early bone health surveillance, including fracture assessment and densitometric evaluation, may facilitate timely diagnosis and improve management of bone complications in patients with Joubert syndrome.

Fulminant myocarditis (FM) is a severe, rapidly progressive and life-threatening condition of myocarditis associated with infectious or autoimmune etiologies. Here, we present three patients with an invasive thymoma who had FM, which eventually led to sudden death. The most frequent clinical presentations at onset include palpitations, orthopnea, and acute worsening of myasthenia gravis (MG). Highly elevated myocardial biomarkers and positive autoantibodies against cardiac muscle, skeletal muscle, and neuromuscular junctions were detected in serum. The electrocardiograph (ECG) findings progressed to life-threatening ventricular arrhythmias. Although high-dose methylprednisolone or intravenous immunoglobulin was administered along with advanced respiratory support, profound hemodynamic collapse rapidly occurred, and these patients eventually died within days. This case series underscores the importance of rapid recognition of FM associated with thymoma and early aggressive supportive and immunomodulatory interventions, including consideration of mechanical circulatory support when clinically indicated.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, most often caused by the m.3243A>G mitochondrial DNA variant, represents one of the most clinically significant inherited mitochondrial disorders. This variant disrupts mitochondrial tRNALeu(UUR) function, leading to impaired mitochondrial protein synthesis and progressive multisystem dysfunction. This narrative review synthesizes recent clinical trials, therapeutic advances, and emerging disease-modifying strategies for m.3243A>G-associated MELAS, with emphasis on evidence published between 2024 and 2026, drawing on PubMed/MEDLINE, Embase, the Cochrane Library, ClinicalTrials.gov, and the EU Clinical Trials Register. Key advances include: i) regulatory approval of high-dose taurine supplementation (9–12 g/day), which achieved complete prevention of stroke-like episodes in 60% of participants in a phase III trial; ii) phase IIb data (company-reported) indicating that sonlicromanol (KH176) showed signals of improvement in cognition, mood, and fatigue, supporting progression to a phase III registrational trial (KHENERFIN, NCT06451757); iii) ongoing trials of zagociguat and TTI-0102 targeting vascular dysfunction and oxidative stress; iv) KL1333, a novel NAD+ modulator, in phase II evaluation (FALCON trial); and v) promising preclinical gene-based approaches—including mitochondria-targeted TALENs, DdCBE base editors, and mitoARCUS nucleases—demonstrating heteroplasmy shifting in patient-derived cells and animal models, though direct clinical applicability to m.3243A>G MELAS requires further investigation. The therapeutic landscape for MELAS is evolving from symptomatic care toward mechanism-based disease modification, led by taurine as the first regulatory-approved disease-modifying therapy and complemented by late-stage small molecules and mitochondrial genome-editing technologies.

Reports of cutaneous lymphomas (CL) following dupilumab administration are increasingly being documented, most frequently in patients with atopic dermatitis (AD). However, information regarding the association between CL and other biologic agents (nemolizumab, tralokinumab, or lebrikizumab) used for the treatment of AD is limited. To date, no large-scale pharmacovigilance study has systematically evaluated this issue in Japan. Therefore, we conducted a case investigation and disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database. Reports registered between April 2004 and August 2025 were analyzed. Both frequentist and Bayesian disproportionality analyses were performed using the reporting odds ratio (ROR) and information component (IC). In the primary analysis, including all reports in the JADER database, the ROR for dupilumab was 257.64 (95% confidence interval [CI], 164.50–404.39), and the IC was 4.52 (IC₀₂₅ = 3.89). For nemolizumab, the ROR was 169.13 (95% CI, 61.78–463.00), and the IC was 2.29 (IC₀₂₅ = 0.95). Reports of CL following tralokinumab or lebrikizumab administration were rare (one and zero cases, respectively) and did not meet the criteria for ROR calculation due to the small number. For sensitivity analysis, disproportionality analyses were restricted to reports with available data on age and sex, submitted by physicians, and cases involving no other suspected drugs. Under these conditions, safety signals based on both the ROR and IC were detected only for dupilumab. The safety signals identified in this study are exploratory in nature and require confirmation in future epidemiological studies.

Fabry disease is an X-linked lysosomal storage disorder caused by pathogenic variants in the α-galactosidase A (α-Gal A, GLA) gene. The disease exhibits substantial clinical heterogeneity, with renal injury representing one of its most prominent manifestations. Due to the scarcity of human renal specimens and the inability of conventional animal models to recreate patient-specific pathological features, the precise mechanism underlying renal-predominant Fabry disease remains poorly understood. In this study, we successfully established and comprehensively characterized a urine-derived induced pluripotent stem cell (iPSC) line from a 35-year-old male patient with classic Fabry disease with a typical renal-dominant phenotype. The patient carried the GLA c.1080_1082delTGG (p.Gly361del) variant. Non-integrating episomal reprogramming was used to generate monoclonal iPSCs, which were further validated for pluripotency, trilineage differentiation ability, genomic stability, and exogenous vector clearance. The established iPSC line stably retained the patient-specific pathogenic variant, exhibited full pluripotent properties, and showed no genomic abnormality or residual episomal integration. Therefore, this well-characterized renal-phenotype-specific iPSC line provides a reliable cellular platform for investigating the mechanisms of progressive Fabry disease nephropathy and can facilitate future targeted drug screening.

Biallelic variants in a family with sequence similarity 149 member B1 gene (FAM149B1, OMIM #618413) causes a range of abnormal phenotypes associated with Joubert syndrome (JS) in humans. However, the phenotypic spectrum and genetic evidence linking FAM149B1 to ciliopathies remain limited, with no prenatal cases previously described. Here, we report the first prenatal case from a non-consanguineous Chinese family presenting with isolated right pelvicalyceal and ureteral dilation at 24 weeks of gestation. Notably, the fetus lacked cerebellar malformations or hallmark neuroimaging features such as molar tooth sign (MTS). Trio-whole-exome sequencing (Trio-WES) identified novel compound heterozygous loss-of-function variants in FAM149B1: paternal c.279T>A (p.Tyr93*) and maternal c.574dup (p.Ser192Phefs*7). Both variants are predicted to trigger nonsense-mediated mRNA decay (NMD), consistent with a loss-of-function mechanism, and parental segregation confirmed asymptomatic heterozygous carrier status, supporting autosomal recessive inheritance. Gene-disease validity assessment assigned a "Strong" classification to FAM149B1-related ciliopathy under ClinGen guidelines, enabling definitive classification of the variants as pathogenic or likely pathogenic. This case expands the phenotypic spectrum of FAM149B1-related disorders to include isolated urinary tract malformations in the prenatal period, where neurological manifestations may be absent or subtle. Our findings highlight the utility of prenatal exome sequencing in atypical cases and contribute to the understanding of the expanding genetic and phenotypic landscape of ciliopathies.