Biomedical subjects

Lisa A Bastarache

Publications and source records attributed to Lisa A Bastarache.

3 recordsLinked to original sources

PubMed2026

Sex-Based Disparities in Fabry Disease Cause Challenges in Newborn Screening.

INTRODUCTION: Fabry disease (FD) is a multi-systemic, X-linked lysosomal storage disorder caused by decreased α-galactosidase activity. Early diagnosis enables timely treatment, but enzyme-based newborn screening (NBS) may not detect affected females. We hypothesized that enzyme-based NBS limitations contribute to sex-based diagnostic disparities in FD and investigated these differences. METHODS: Retrospective cohort analyses used data from the Fabry Registry (FR: 2001-2023) and Tennessee NBS (2017-2024). Sex differences in diagnosis via NBS, biochemical phenotype, symptom onset, and treatment initiation were analyzed using Wilcoxon and chi-square tests. RESULTS: Among 8,657 FR individuals, 73 (67 males, 6 females) were identified via NBS. FR data show that affected females had significantly higher residual α-galactosidase activity than affected males (leukocyte median: 45.9% vs. 3.9%, plasma median: 32.5% vs. 3.9%; p < 0.0001 for both). FR females had delayed symptom onset (18.1 vs. 11.1 years), later diagnosis (35.5 vs. 30.8 years), and lower treatment rates (51.1% vs. 80.8%) compared to males (all %, p < 0.0001). Tennessee NBS detected 25 males but no females. CONCLUSION: Females with FD have delays in symptom onset, diagnosis, and treatment compared to males. Furthermore, higher residual enzyme activity causes current enzyme-based NBS to miss most females. Incorporating sex-specific cutoffs and/or molecular sequencing into NBS could improve early detection and reduce sex-based disparities.

Humans↗

PubMed2026

Sex-Specific Diagnostic Inequality in Fabry Disease: Lessons Learned from Analysis of Newborn Screening and Cascade Testing in Tennessee from 2017 to 2024.

INTRODUCTION: Fabry disease (FD) is an X-linked lysosomal storage disease caused by alpha-galactosidase A (aGAL) deficiency. Newborn screening (NBS) programs for FD have been implemented in several US states; however, its effectiveness in identifying affected females remains uncertain. We hypothesized that sex-specific inequality of NBS-based detection of FD results in different diagnostic pathways for males and females with FD. METHODS: We compared diagnostic approaches for males and females with FD using Tennessee NBS results and Vanderbilt Lysosomal Storage Disorders Database (VLSDD). Sex-specific detection differences were assessed using Fisher's exact test (α = 0.05). RESULTS: Tennessee NBS identified 25 males but no females with FD from 2017 to 2024. In VLSDD, among 81 individuals with FD, sex distribution was nearly equal (42 males, 39 females). Among males, 26/42 (62%) were diagnosed via NBS, 7/42 (17%) through known family history, and 9/42 (21%) based on clinical symptoms. All 16 males diagnosed through non-NBS were born before its implementation. In contrast, none of the 39 females were diagnosed through NBS (p value <0.05). Of these, 13/39 (33%) were diagnosed through cascade testing following their sons' detection by NBS, with a median age at diagnosis of 28 years (25th-75th percentile: 24.5-34.0). Of the remaining 26 females, 12/26 (46%) were diagnosed after a family member was diagnosed through clinical symptoms and 14/26 (54%) were diagnosed through clinical symptoms. CONCLUSIONS: NBS effectively identifies affected males but fails to detect females with FD, though it can indirectly facilitate diagnosis of older female relatives.

Humans↗

PubMed2025

Germline Variants Influence Chronic Liver Disease Progression through Distinct Pathways.

Cirrhosis and hepatocellular carcinoma (HCC) are long-term complications of chronic liver disease (CLD). In this large multi-ancestry genome-wide association study of all-cause cirrhosis (35,481 cases, 2.36M controls) and HCC (6,680 cases, 1.76M controls), we identified 27 loci associated with cirrhosis (10 novel) and 11 with HCC (three novel). Three novel cirrhosis loci were replicated in independent cohorts (e.g. FGF21, RPTOR, and IFNL3/4). Fifteen cirrhosis loci exhibited differential effects on cirrhosis risk via underlying etiologies, and six HCC loci influenced HCC risk indirectly via cirrhosis. In a gene-burden analysis of rare variants from whole-genome sequencing data in the VA Million Veteran Program (n=102,677), we identified GSTA5 as a novel cirrhosis-associated gene, while APOB and ATP9B were associated with and replicated for HCC. A high genetic risk score for cirrhosis was associated with a nearly doubled risk of CLD progressing to cirrhosis (HR=1.94, P=2×10-68) and of cirrhosis progressing to HCC (HR=1.65, P=7×10-08). Finally, among individuals with chronic hepatitis C who underwent antiviral therapy, cirrhosis risk was modified by variants in PNPLA3, IFNL3/4, and CD81 following pegylated interferon-α therapy, and by APOE lead variant following direct-acting antiviral therapy. These findings provide new insights into the complex genetic architecture of CLD progression with potential clinical and therapeutic implications.

Journal Article↗