| domain | key finding/statistic | evidence type | source/year |
|---|---|---|---|
| Ophthalmology / natural history | Mild PEX1-mediated ZSD cohort: n=10 from 6 families; 9/10 homozygous PEX1 c.2528G>A (p.Gly843Asp); median age 22.6 y; symptom onset median 6 months; RP-like phenotype with stable BCVA over 10.8 y; SD-OCT abnormalities in all evaluated patients (pqac-00000001, pqac-00000002) | Human clinical, cross-sectional with longitudinal visual follow-up | Karuntu et al., 2024 |
| Biomarkers / screening | LC-MS/MS study of n=598 samples including 19 PBD patients with PEX1/PEX6 deficiency found elevated dicarboxylic acylcarnitines; C20-DC elevated in 100% and C22-DC in 68% of PBD patients; proposed as orthogonal follow-up to elevated C26:0-lysoPC, not standalone diagnostic markers (pqac-00000010, pqac-00000014) | Human biochemical diagnostics | Wangler et al., 2023 |
| Therapy / bile acids | Cholic acid extension: 17 patients continued in extension; 22 total analyzed. CA suppressed toxic C27 bile acid intermediates (DHCA/THCA), but no clinically relevant improvement in liver tests, elastography, coagulation, fat-soluble vitamins, or weight after 21 months; advanced liver disease subgroup had worsening bilirubin/transaminases and CA could be harmful (pqac-00000012, pqac-00000013) | Human interventional extension study | Klouwer et al., 2018 |
| Therapy / pexophagy modulation | In four PEX1-G843D cell types including primary patient fibroblasts, chloroquine, hydroxychloroquine, and 3-methyladenine did not restore peroxisomal function and instead worsened matrix-protein import/metabolic readouts; ATG5/NBR1 knockdown gave only minimal improvement; L-arginine remained more promising (pqac-00000011) | In vitro patient-cell mechanistic/therapeutic study | Klouwer et al., 2021 |
| Mechanism / liver disease model | Pex1-G844D mouse model of mild ZSD shows progressive hepatopathy from hepatomegaly to inflammation, fibrosis, tumors/HCC-like changes; severe import defect with catalase mislocalization; secondary mitochondrial dysfunction; elevated VLCFA, pristanic/phytanic acids, C27 bile acid intermediates, C26:0-lysoPC; decreased plasmalogens and dysregulated hepatic lipid homeostasis (pqac-00000005, pqac-00000007, pqac-00000008, pqac-00000009) | Model organism, longitudinal mechanistic study | Chen et al., 2025 preprint |


*Table: This compact table summarizes key clinical, biomarker, treatment, and mechanistic evidence for PEX1-related non-classic Zellweger spectrum disorder. It highlights the most decision-relevant findings from recent human cohorts, therapeutic studies, and the Pex1-G844D mouse model.*