Abstract
A girl with a proven diagnosis of I-cell disease is presented. Proximal tubular dysfunction was characterized by increased excretion of low molecular proteins, aminoaciduria, hyperphosphaturia, and high/slightly increased urinary calcium. The concentration of 1,25-dihydroxycalciferol in serum was increased. Rickets were present on X-rays. As the proximal tubular dysfunction resembles the dysfunction in Dent disease, one can speculate about a common pathogenesis. Impairment of acidification in lysosomes due to loss of function of the chloride-5 channel impairs intralysosomal protease activity in Dent disease, while in I-cell disease the intralysomal protease activity is lacking.
This is a preview of subscription content, log in via an institution to check access.
References
Bocca G, Noordam C, Wevers RA, Jong JG de, Meer W van der, Keijzer MH de, Korver CR, Smeitink JA (2000) I-Cell disease presenting with severe hypophosphatemia and cardiomyopathy. Neuropediatrics 31:49–50
Beck M, Barone R, Hoffmann R, Kratzer W, Rakowsky T, Nigro F, Fiumara A (1995) Inter- and intrafamilial variability in mucolipidosis II (I-cell disease). Clin Genet 47:191–199
Pazzaglia UE, Beluffi G, Danesino C, Frediani PV, Pagani G, Zatti G (1989) Neonatal mucolipidasis 2. The spontaneous evolution of early bone lesions and the effect of vitamin D treatment. Report of two cases. Pediatr Radiol 20:80–84
Martin JJ, Leroy JG, Eygen M van, Ceuterick C (1984) I-cell disease: a further report on its pathology. Acta Neuropathol (Berl) 64:234–242
Kornfeld S (1986) Trafficking of lysosomal enzymes in normal and disease states. J Clin Invest 77:1–6
Pook MA, Wrong O, Wooding C, Norden AG, Feest TG, Thakker RV (1993) Dent's disease, a renal Fanconi syndrome with nephrocalcinosis and kidney stones, is associated with a microdeletion involving DXS255 and maps to Xp11.22. Hum Mol Genet 2:2129–2134
Igarashi T, Inatomi J, Ohara T, Kuwahara T, Shimadzu M, Thakke RV (2000) Clinical and genetic studies of CLCN5 mutations in Japanese families with Dent's disease. Kidney Int 58:520–527
Jentsch TJ, Stein V, Weinreich F, Zdebib AA (2002) Molecular structure and physiological function of chloride channels. Physiol Rev 82:503–568
Marshansky V, Ausiello DA, Brown D (2002) Physiological importance of endosomal acidification: potential role in proximal tubulopathies. Curr Opin Nephrol Hypertens 11:527–537
Devuyst OO, Guggino WR (2002) Chloride channels in the kidney: lessons learned from knock-out animals. Am J Physiol Renal Physiol 283: F1176–F1191
Herak-Kramberger CM, Brown D, Sabolic I (1998) Cadmium inhibits vacuolar H+ ATPase and endocytosis in rat kidney cortex. Kidney Int 53:1713–1726
Takano M, Nakanishi N, Kitahara Y, Sasaki Y, Murakami T, Nagat J (2002) Cisplatin-induced inhibition of receptor-mediated endocytosis of protein in the kidney. Kidney Int 62:1707–1717
Kornfeld S, Sly WS (2001) I-cell disease and pseudo-Hurter polydystrophy: disorders of lysosomal enzyme phosphorylation and localization. Metabolic and molecular basis of inherited disease. McGraw-Hill, pp 3469–3480
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Bocca, G., Monnens, L.A.H. Defective proximal tubular function in a patient with I-cell disease. Pediatr Nephrol 18, 830–832 (2003). https://doi.org/10.1007/s00467-003-1213-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-003-1213-2