Pediatrik Başlangıçlı Kalıtsal Metabolik Bozukluklarda Çoklu Lokus Moleküler Bulgular: Tayvan'da Sekiz Yıllık Dış Kaynaklı Genomik Test Serisi

Özet (abstract)

Background/Objectives: Outsourced genomic testing can identify additional findings in patients with inherited metabolic disorders (IEMs), including lysosomal storage diseases. We examined these findings in a selected Taiwanese series. Methods: We retrospectively reviewed 13 patients referred during 2018–2025 with a reported or suspected metabolic diagnosis. Whole-exome sequencing (WES) was initially used mainly after inconclusive testing or for incompletely explained phenotypes and was used more broadly later. The original registry also records whole-genome sequencing (WGS) for two included patients. We distinguished reported gene-level findings from diagnoses supported by pathogenic or likely pathogenic (P/LP) variants at each locus. Results: The 13 patients had 18 reported gene-level findings comprising 27 variants. Five met the inclusive multi-locus definition (38.5%; exact 95% confidence interval, 13.9–68.4%). The proportion was 30.8% after excluding candidate gene–disease associations and 7.7% when P/LP variants in the expected zygosity were required at both loci using the later case-summary classifications. Several classifications differed between the original registry and later summaries. These estimates are not directly comparable with the published 4.9% benchmark because ascertainment and diagnostic definitions differ. Enzyme replacement therapy was documented in three patients, including one treated before WES. Conclusions: Unexplained features may warrant evaluation for an additional diagnosis. The selected sample and differing levels of diagnostic certainty limit estimates of confirmed multi-locus disease.

Yazarların özeti; kaynağından alınmıştır. Diagnostics, 2026 · DOI ↗