Severe Fanconi Syndrome with Fracturing Osteopathy in a Young Adult: Late Revelation of Dent Disease at Age 37
Abstract
A 37-year-old man from a consanguineous family presented with diffuse bone pain, recurrent fractures, and a waddling gait. Laboratory workup revealed severe hypophosphatemia (17 mg/L), markedly elevated alkaline phosphatase, hypercalciuria three times above normal, glycosuria, tubular proteinuria (450 mg/24h), nephrocalcinosis, and hyperchloremic metabolic acidosis. Bone imaging revealed diffuse demineralization, vertebral compression fractures, and a honeycomb appearance of the vertebrae ("beehive" aspect). The association of chronic hypophosphatemia, hypercalciuria, nephrocalcinosis, and tubular proteinuria pointed toward a clinical diagnosis of Dent disease. Genetic analysis was not feasible locally, as no genetic testing for hereditary nephropathies is currently available in Algeria and export of blood samples is restricted; a private send-out to CERBA (France) was cost-prohibitive for the patient. The diagnosis therefore remains purely clinical. This X-linked disorder (mutations in CLCN5 or OCRL) combines hypercalciuria, nephrocalcinosis, low-molecular-weight proteinuria, and incomplete Fanconi syndrome. Chronic hypophosphatemia is responsible for severe osteomalacia. Management relies on oral phosphate supplementation, acidosis correction, and treatment of hypercalciuria (low-salt diet, thiazide diuretics).
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References
- Devuyst, O. and R.V. Thakker, Dent's disease. Orphanet J Rare Dis, 2010. 5: p. 28.
- Matsumoto, A., et al., Severe Osteomalacia with Dent Disease Caused by a Novel Intronic Mutation of the CLCN5 gene. Intern Med, 2018. 57(24): p. 3603–3610.
- John C Lieske, M., Dawn S Milliner, MD, Lada Beara-Lasic, MD, Peter Harris, PhD, Andrea Cogal, BS, and Elizabeth Abrash, BA., Dent Disease. GeneReviews®, 2012 Aug 9 [Updated 2017 Dec 14].
- Ye, Q., et al., Multicenter study of the clinical features and mutation gene spectrum of Chinese children with Dent disease. Clin Genet, 2020. 97(3): p. 407–417.
- Wrong, O.M., A.G. Norden, and T.G. Feest, Dent's disease; a familial proximal renal tubular syndrome with low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, metabolic bone disease, progressive renal failure and a marked male predominance. Qjm, 1994. 87(8): p. 473–93.
- Annigeri, R.A. and R. Rajagopalan, Hypophosphatemic rickets due to Dent's disease: A case report and review of literature. Indian J Nephrol, 2009. 19(4): p. 163–6.
- Anglani, F., et al., Nephrolithiasis, kidney failure and bone disorders in Dent disease patients with and without CLCN5 mutations. Springerplus, 2015. 4: p. 492.
- Claverie-Martín, F., E. Ramos-Trujillo, and V. García-Nieto, Dent's disease: clinical features and molecular basis. Pediatr Nephrol, 2011. 26(5): p. 693–704.
- Raja, K.A., et al., Responsiveness of hypercalciuria to thiazide in Dent's disease. J Am Soc Nephrol, 2002. 13(12): p. 2938–44.
- Amer-Mestre, M., et al., Recurring renal lithiasis due to Dent's disease. Urol Case Rep, 2023. 50: p. 102484.