Browsing by Subject "Lysosomal storage disorder"

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    Exploratory Study on the Challenges of Newborn Screening for Lysosomal Storage Disorders Emphasizes the Need for Multitier Testing and Collaborative Approaches to Management
    (Springer, 2025-06-16) Terrell, A.; Sapp, K.; Graham, B.; McPheron, M.; Wetherill, L.; Medical and Molecular Genetics, School of Medicine
    Innovative treatments have allowed the introduction of conditions such as lysosomal storage disorders (LSDs) to newborn screening (NBS). This study explored the challenges healthcare providers faced with the addition of LSDs to NBS and identified adjustments that minimized the burden of such challenges. An online survey was distributed to healthcare providers with experience working with patients with LSDs. The most common anticipated challenges were interpreting NBS results (75%) and having adequate screening protocols (63%). After the addition of LSDs, interpretation of newborn screen results (64%) remained a challenge, but adequate screening protocols were less frequent (25%). Collaboration of care with additional subspecialty providers was the most common change in clinic structure (68%) and individual practice (54%) after the addition of LSDs to NBS. Given the interpretation of results remained a challenge most providers faced, we advocate the implementation of multitier screening protocols is key to improving sensitivity and specificity of NBS for LSDs. This allows for the identification of at-risk infants and provides clarity on expected phenotypes and healthcare needs. These results indicate collaboration between healthcare providers is a key factor in providing optimal care. The findings of this study may benefit clinics that are implementing NBS for LSDs as the adoption of these practices preemptively may reduce the burden of that challenge.
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    Therapeutic efficacy of rscAAVrh74.miniCMV. LIPA gene therapy in a mouse model of lysosomal acid lipase deficiency
    (Elsevier, 2022-08-04) Lam, Patricia; Ashbrook, Anna; Zygmunt, Deborah A.; Yan, Cong; Du, Hong; Martin, Paul T.; Pathology and Laboratory Medicine, School of Medicine
    Lysosomal acid lipase deficiency (LAL-D) presents as one of two rare autosomal recessive diseases: Wolman disease (WD), a severe disorder presenting in infancy characterized by absent or very low LAL activity, and cholesteryl ester storage disease (CESD), a less severe, later onset disease form. Recent clinical studies have shown efficacy of enzyme replacement therapy for both forms of LAL-D; however, no gene therapy approach has yet been developed for clinical use. Here, we show that rscAAVrh74.miniCMV.LIPA gene therapy can significantly improve disease symptoms in the Lipa -/- mouse model of LAL-D. Treatment dramatically lowered hepatosplenomegaly, liver and spleen triglyceride and cholesterol levels, and serum expression of markers of liver damage. Measures of liver inflammation and fibrosis were also reduced. Treatment of young adult mice was more effective than treatment of neonates, and enzyme activity was elevated in serum, consistent with possible bystander effects. These results demonstrate that adeno associated virus (AAV)-mediated LIPA gene-replacement therapy may be a viable option to treat patients with LAL-D, particularly patients with CESD.