- Research Article
- 10.1007/s00467-025-07020-9
Unveiling long-standing low-molecular-weight proteinuria: A proximal tubular mitochondrial enzyme impairment caused by EHHADH mutation.
- Oct 21, 2025
- Pediatric nephrology (Berlin, Germany)
- Hiroshi Tanaka + 5 more +5
The energy requirement of renal proximal tubular cells depends on mitochondrial fatty acid β-oxidation. Enoyl-CoA hydratase-l-3-hydroxyacyl-CoA dehydrogenase (EHHADH) is a crucial enzyme in mitochondrial fatty acid oxidation, and mutations in EHHADH reportedly cause Fanconi syndrome. Here, we report the case of a 28-year-old Japanese woman with a long-term history of low-molecular-weight proteinuria (LMWP) who exhibited a missense mutation in the EHHADH gene. She was diagnosed with LMWP at 4years of age. The search for the CLCN5 gene was unremarkable, and kidney biopsy revealed no significant tubulointerstitial changes. The LMWP persisted, and glucosuria gradually developed thereafter. Unexpectedly, next-generation sequencing identified a heterozygous missense mutation in the EHHADH gene. Her father, who harbored LMWP, also had the same mutation. Furthermore, immunostaining of the stored kidney specimens showed decreased immunoreactivity for cytochrome coxidase subunit 4 in the proximal tubules, suggesting an underlying mitochondrial impairment.
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