脊髄性筋萎縮症

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder caused by biallelic mutations in the SMN1 gene, leading to progressive motor neuron degeneration, muscle weakness and atrophy due to survival motor neuron (SMN) protein deficiency. The Taiwan Child Neurology Society convened 17 pediatricians with extensive clinical experience in SMA to establish a consensus on gene therapy for SMA in Taiwan. Epidemiological data indicate that approximately one in 48 individuals in Taiwan is an SMA carrier, and one in 17,181 newborns is affected. The advent of three FDA-approved disease-modifying therapies-onasemnogene abeparvovec, nusinersen, and risdiplam-has markedly improved therapeutic prospects. Early intervention in presymptomatic infants significantly enhances motor development and the ability to walk independently. In 2023, onasemnogene abeparvovec was officially included in Taiwan's National Health Insurance, reducing the financial burden on patients and improving prognosis. This consensus recommends incorporating SMA into the newborn screening program for early diagnosis and prompt treatment, and emphasizes that gene therapy should be evaluated based on SMN2 copy number and clinical condition. Presymptomatic treatment is critical for optimal motor outcomes, and multidisciplinary care teams are essential for comprehensive long-term management.

Objective: To summarize the clinical characteristics and management of hypoglycemia in children with spinal muscular atrophy (SMA). Methods: Case series study was conducted. Clinical data from 5 children with SMA and hypoglycemia who were treated at the Peking University First Hospital from January 2020 to December 2025 were collected and analyzed. The precipitating factors, clinical manifestations, laboratory findings, treatment, and prognosis of hypoglycemia were summarized. Results: Of the 5 children, 1 was male and 4 were female, and all had 5q SMA type 2. Hypoglycemia occurred 0.7-2.5 years after the initiation of disease-modifying therapy. The age at the first hypoglycemia episode occurred 5-13 years. Hypoglycemia occurred after an acute infection in 3 children and following fasting for routine follow-up examinations in the other 2 children. Three children had hypoglycemia-related symptoms, including vomiting, abdominal pain, hand tremor, sweating, and fatigue, whereas the other 2 children were asymptomatic. Urinary ketones were positive in all 5 children, 4 children had concurrent metabolic acidosis, and 4 children had serum creatinine levels below the age-specific reference range. Hypoglycemia was rapidly corrected in all 5 children after intravenous glucose administration or oral intake of glucose-containing beverage. Conclusions: Children with SMA may develop hypoglycemia, particularly during infection or fasting. Because its clinical manifestations of hypoglycemia may be nonspecific, clinicians should maintain a high level of vigilance, avoid prolonged fasting, and ensure timely energy supplementation. Hypoglycemia should remain a clinical consideration in patients receiving disease-modifying therapy.

Genetic neurodevelopmental disorders (NDDs) encompass a heterogeneous group of conditions characterized by impaired cognitive, behavioral, and neurological development resulting from pathogenic variants affecting brain development and synaptic function. Advances in molecular genetics and next-generation sequencing have significantly expanded the understanding of the genetic architecture underlying disorders such as Rett syndrome (RTT), Fragile X syndrome (FXS), Angelman syndrome (AS), and autism spectrum disorders. Beyond these classical neurodevelopmental disorders, spinal muscular atrophy (SMA) is included as a paradigmatic example of successful RNA-based therapeutic translation. Concurrently, RNA-based therapeutics have emerged as promising precision medicine strategies capable of modulating gene expression at the transcriptional and post-transcriptional levels. These approaches include antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), messenger RNA (mRNA) therapies, RNA editing technologies, and splice-modulating agents. Recent clinical successes, particularly in spinal muscular atrophy, have demonstrated the transformative potential of RNA therapeutics in neurological disease. However, substantial challenges remain, including BBB penetration, long-term safety, immune activation, and genotype-specific variability in therapeutic response. This review summarizes current advances in RNA-based therapeutics for genetic NDDs, highlighting molecular mechanisms, disease-specific therapeutic strategies, translational progress, delivery challenges, and future directions. Overall, continued progress will depend on the integration of disease biology, rational RNA therapeutic design, and effective CNS-targeted delivery, supporting the broader implementation of precision RNA medicine for genetic neurodevelopmental disorders.

Adenine base editors (ABEs), which achieve A·T to G·C conversions in the genome precisely, symbolize a groundbreaking development in genetic engineering across animal, plant, and microbial systems. This review systematically summed up the research progress and current challenges of ABE in medical and biological applications: it outlined the historical context and pivotal milestones of its technological development; it emphasized major therapeutic advances for genetic diseases including spinal muscular atrophy, mitochondrial genetic disorders, and hyperlipidemia; it provided a comprehensive overview of its prospective uses for enhancing genetic traits in agricultural crops, including grains and fruits; this review conducted a multidimensional assessment of ABE performance through systematic comparison with other base editing technologies, comprehensively evaluating both editing efficiency and inherent limitations. It specifically addresses biosecurity risks such as off-target effects and genomic instability. Finally, safety concerns were proposed as the central challenge hindering its clinical translation, although ABE holds immense promise for precision medicine and agricultural breeding. Unlike previous reviews that mainly summarized early ABE development and general applications, this review particularly emphasizes recently engineered ABE systems, translational bottlenecks, delivery strategies, comparative clinical feasibility, and unresolved biosafety challenges that currently limit broader therapeutic and agricultural applications.

Introduction. Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease caused by the loss of the SMN1 gene, with a variable clinical spectrum determined primarily by the number of copies of the SMN2 gene. The development of new therapies underscores the importance of early molecular diagnosis and genotype-phenotype characterization. Objective. To describe 27 years of experience in the molecular diagnosis of SMA at a pediatric referral hospital in Argentina and to evaluate the correlation between SMN2 copy number and the SMA types.Population and methods. A retrospective descriptive study was conducted on 1060 pediatric patients with clinically suspected SMA who were evaluated between 1997 and 2024. Molecular diagnosis was performed using PCR-RFLP and, since 2012, MLPA to determine SMN1 and SMN2 copy number. Genotype-phenotype correlation was evaluated in 260 patients with complete clinical characterization. Results. The diagnosis was confirmed in 513 patients. A homozygous deletion of the SMN1 gene was detected in 99.6% of unrelated cases. The positivity rate increased over time. A significant correlation was observed between the number of SMN2 copies and the type of SMA, with milder phenotypes associated with a higher number of copies. Conclusion. Molecular diagnosis of SMA enabled accurate and timely characterization of patients, avoiding invasive procedures and optimizing therapeutic decision-making. Genotype-phenotype correlation is a fundamental tool for prognosis and clinical management, highlighting the importance of an interdisciplinary approach.