Abstract
Medullary cystic kidney disease type 2 is an uncommon autosomal dominant condition characterized by juvenile onset hyperuricemia, precocious gout and chronic renal failure progressing to end-stage renal disease in the 4th through 7th decades of life. A family suffering from this condition is described. The patient in the index case presented with renal insufficiency as a child. A renal biopsy revealed tubular atrophy, and immunohistochemical staining of the tissue for uromodulin (Tamm Horsfall protein) revealed dense deposits in renal tubular cells. Genetic testing revealed a single nucleotide mutation (c.899G>A) resulting in an exchange of a cysteine residue for tyrosine (C300Y). Medullary cystic kidney disease type 2 (also known as uromodulin-associated kidney disease) likely represents a form of endoplasmic reticulum storage disease, with deposition of the abnormal uromodulin protein in the endoplasmic reticulum, leading to tubular cell atrophy and death.
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Acknowledgements
This grant was supported in part by United States Public Health Service research grant DK62252 from the National Institute of Diabetes and Digestive and Kidney Diseases and by a grant from the National Kidney Foundation of North Carolina, Inc. The authors wish to thank Vicki Robins, R.N., and Rachel Frank, R.N., C.N.N., for their assistance with this manuscript. Antibody to Tamm Horsfall protein was kindly provided by John Hoyer, M.D., Children’s Hospital of Philadelphia, Philadelphia, PA. Three of the authors (AJB, TCH and MCG) and their institutions have entered a licensing agreement with Athena Diagnostics, Inc., for uromodulin mutational analysis.
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Bleyer, A.J., Hart, T.C., Willingham, M.C. et al. Clinico-pathologic findings in medullary cystic kidney disease type 2. Pediatr Nephrol 20, 824–827 (2005). https://doi.org/10.1007/s00467-004-1719-2
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DOI: https://doi.org/10.1007/s00467-004-1719-2