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.
Yuh-Jyh Jong, Yin-Hsiu Chien, Wen-Chen Liang et al.· Journal of the Formosan Medi...· 0 citations
Cardiovascular disease is a leading cause of morbidity and premature mortality in many inherited syndromic and metabolic disorders. However, its cardiac manifestations are often recognized late and are rarely described collectively within a single cohort. We reviewed eight years of outsourced next-generation sequencing (NGS) requested through the pediatric genetics service of a single tertiary center in Taiwan and identified 22 patients with molecularly confirmed genetic disorders and documented cardiovascular involvement. For each patient, the causative genotype—including lysosomal storage diseases, RASopathies, CHARGE syndrome, connective-tissue disorders, primary cardiomyopathies and channelopathies, neuromuscular disorders, contiguous-gene syndromes, and other metabolic and syndromic conditions—was mapped to a structured echocardiographic phenotype. Septal defects or shunts and valvular regurgitation were the most common findings (10/22 and 9/22, respectively), followed by septal hypertrophy, valvular stenosis, and great-vessel or aortic abnormalities. Two children had left ventricular systolic dysfunction, and one died following an out-of-hospital cardiac arrest. Several cardiac lesions clustered by disease category, most notably valvular thickening in mucopolysaccharidoses and elastin arteriopathy in Williams–Beuren syndrome. These genotype-to-cardiac phenotype patterns support the need for gene-informed, systematic cardiac surveillance rather than symptom-driven referral in children with these disorders.
Chung-Lin Lee, Ya-Hui Chang, Chih-Kuang Chuang et al.· International Journal of Mol...· 0 citations
Inherited mitochondrial cardiomyopathies arise from pathogenic variants affecting oxidative phosphorylation, mitochondrial DNA maintenance, cardiolipin remodeling, protein import, cofactor metabolism, and mitochondrial dynamics or proteostasis. These disorders may be cardiac-predominant or part of multisystem disease. Their overlapping cardiac phenotypes suggest convergence on interacting pathways of energetic stress, cristae disruption, calcium imbalance, and redox injury, but do not establish a universal requirement for defective mitophagy. Mitochondrial quality control encompasses protein surveillance, membrane remodeling, dynamics, biogenesis, and organelle disposal; mitophagy is one component. We critically examine the hypothesis that inadequate clearance of damaged mitochondria contributes to progression in a subset of genotypes and disease stages. Disease-specific studies provide support in selected Barth syndrome models, whereas findings in frataxin deficiency vary with model and assay. We distinguish mitochondrial delivery to lysosomes, dynamic turnover measurements, and changes in pathway markers, and identify indirect evidence from acquired heart disease and fatty acid oxidation deficiency. Therapeutic evidence is separated into cellular, animal, and human studies and approved indications. Elamipretide has accelerated approval for muscle-strength improvement in patients with Barth syndrome weighing at least 30 kg; cardiac disease modification remains unconfirmed. Gene replacement has reached early clinical testing, including adeno-associated virus-mediated frataxin gene delivery (AAV-FXN), whereas mitochondrial genome editing and selective mitophagy modulation remain investigational. We propose testable predictions addressing progression, selective rescue, and treatment timing, together with outcomes that would challenge the hypothesis. This framework supports genotype- and stage-specific investigation without assuming that enhanced mitophagy will benefit every mitochondrial cardiomyopathy.
Chung-Lin Lee, Chih-Kuang Chuang, Ya-Hui Chang et al.· International Journal of Mol...· 0 citations
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