Journal of the Formosan Medical Association最新文献

Hereditary transthyretin amyloidosis (ATTRv) is a fatal autosomal dominant disorder caused by pathogenic variants in the TTR gene. Various variants cause destabilization of transthyretin tetramers and extracellular deposition of misfolded amyloid fibrils in different tissues, resulting in highly variable phenotypes. The peripheral nervous system is the most frequently involved organ, followed by the heart, the eyes, the kidneys, and the gastrointestinal tract. In contrast to the most common p. Val50Met variant in Western countries, the p. Ala117Ser variant constitutes the majority of ATTRv cases in Taiwan. Increased awareness, noninvasive imaging, and genetic testing have improved early identification; however, diagnostic delay remains a significant challenge because of phenotypic heterogeneity and variable penetrance. Recent therapeutic developments-such as transthyretin stabilizers, small interfering RNAs and antisense oligonucleotide-based gene silencing, and investigational gene-editing approaches-have transformed prognosis. This review summarizes the updated evidence concerning the epidemiology, pathophysiology, clinical presentation, and diagnostic strategies, with an emphasis on evolving treatments. Special attention is given to early detection, the integration of multidisciplinary care, and the management of asymptomatic carriers, highlighting the importance of continued research to optimize outcomes for affected individuals.

Adult-onset neurodegenerative diseases (AOND), such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal dementia, severely affect patients' quality of life. Pathogenic single-nucleotide variations (SNVs) and small insertions and deletions (indels) can disrupt genes involving ANOD, and expansion of short tandem repeats such as trinucleotide repeats is an important etiology of hereditary ataxia. Variations in more than one gene combined to create polygenic risk scores (PRS) for multifactorial types of AOND. Recently, genome structural variations (SVs) like copy number variations (CNVs) and expansion of long repeats are increasingly identified as the etiologies of AOND. Tools for molecular diagnosis of AOND have evolved from Sanger sequencing to next-generation sequencing (NGS) such as short-read whole-exome sequencing (WES) and whole-genome sequencing (WGS), and long-read sequencing is especially helpful in solving SVs and expansions of long repeats. Patients might have affected and/or at-risk family members at the time of diagnosis, so genetic counseling for risk handling and birth planning need to be conducted with caution. This review will help readers to better understand the genetic testing for AOND.

Not applicable.

Background: With global aging, neurodegenerative disorders, particularly Alzheimer's disease (AD) and Parkinson's disease (PD), have become major public health concerns. However, the evaluation of their burden trends in Taiwan is lacking. We assessed temporal and geographic trends in the burden of AD with other dementias and PD in Taiwan from 2000 to 2021, stratified by age, sex, and region.

Methods: Data from Taiwan's National Health Insurance (NHI) and National Death Registry were analyzed for 2000-2021. Case definitions for Alzheimer's disease with other dementias (ADODs) and Parkinson's disease (PD) followed Global Burden of Disease 2021 criteria and were identified using ICD codes. Fatal burden was assessed using the National Death Registry. Disease burden was quantified by years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs), with additional geographic mapping to visualize regional variations.

Results: Between 2000 and 2021, age-standardized prevalence rose sharply for ADODs (+885 %) and PD (+394 %), while mortality increased by 116 % and 31 %, respectively; incidence remained stable. DALY rates grew by 258 % for ADODs and 86 % for PD, mainly driven by rising YLDs. The greatest burden was among those aged ≥80 years, with ADODs and PD DALYs increasing by 357 % and 147 %, respectively. Geographically, the highest age-standardized DALYs for ADODs and PD were found in the Southern Taiwan.

Conclusion: The prevalence and health burden of ADODs and PD have increased substantially in Taiwan despite declining incidence, posing growing challenges to the aging population.