Abstract: FR-PO0155
From a Cystinosis Case with Severe Myopathy to an Aging-Like Cellular Phenotype
Session Information
- Hereditary Glomerular and Tubulointerstitial Kidney Diseases
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)
Authors
- Tongu, Yoshiyasu, Department of Nephrology, National Center Hospital for Global Health and Medicine, Shinjuku, Tokyo, Japan
- Katagiri, Daisuke, Department of Nephrology, National Center Hospital for Global Health and Medicine, Shinjuku, Tokyo, Japan
- Shimizu, Yukiko, Department of Laboratory Animal Medicine, Research Institute, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan
- Okamura, Tadashi, Department of Laboratory Animal Medicine, Research Institute, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan
Group or Team Name
- Department of Nephrology, NCGM, JIHS
Background
Nephropathic cystinosis stems from biallelic CTNS mutations and lysosomal cystine accumulation. With longer survival after kidney transplantation, skeletal muscle disease (distal myopathy, dysphagia, respiratory weakness) has become a major late complication, yet its cellular basis remains unclear. We asked whether an aging-like cellular signature underlies it.
Methods
In the index patient with severe muscle involvement, we systematically evaluated motor, respiratory, and swallowing function. From five cystinosis patients and healthy controls, urine-derived cells (UDCs) underwent MyoD1-induced myogenic conversion and bulk RNA sequencing. Biological age was estimated with the transcriptome-based aging clock tAge (developed with the Gladyshev group) and compared to chronological age and clinical phenotype.
Results
A 30-year-old woman developed Fanconi syndrome at age 3, progressed to renal failure, and received a kidney transplant from her father at age 12 without cysteamine. Cystinosis was confirmed at age 30 via leukocyte cystine assay after corneal crystals were noted. Her clinical course was dominated by skeletal muscle disease: distal-predominant myopathy with hand intrinsic atrophy and reduced motor amplitudes, restrictive ventilatory impairment, and dysphagia. She also had thyroid hypoplasia, low bone density, and corneal crystals, reflecting severe untreated multi-organ disease. Transcriptomes of UDC-derived myocytes showed features of premature senescence and disturbed muscle homeostasis, consistent with an aging-like cellular state. Differentially expressed genes were examined as candidate drivers of muscle pathology. tAge values in patient cells exceeded their chronological age. Cysteamine produced a partial systemic response but no clear muscle improvement.
Conclusion
Skeletal muscle disease can dominate the late course of cystinosis and, as in this patient, become severely disabling when treatment is delayed. An aging-like cellular signature may contribute. Patient-derived myogenic cells offer a noninvasive platform for early intervention. Although transplantation has prolonged cystinosis survival, the late aging-like manifestations need urgent attention.
Funding
- Government Support – Non-U.S.