BACKGROUND: Autosomal dominant medullary cystic kidney disease type 1 (MCKD1; Mendelian Inheritance in Man 174000) is a hereditary tubulointerstitial renal disease. For MCKD1, a locus on chromosome 1q21 is published. Although there are characteristic biopsy and imaging findings for MCKD, clinical diagnosis of this disorder is still very difficult because unique phenotypic features are not always present in individual cases. METHODS: In a large Native-American kindred with apparent autosomal dominant nephropathy, clinical findings in more than 50 individuals were collected and evaluated. Haplotype analysis for 34 individuals was performed. RESULTS: We report the difficulties establishing the diagnosis of MCKD in a large Native-American kindred solely by means of clinical criteria. This kindred shows a wider range of age of disease onset than previously reported. Gout and hypertension were common, but no patient reported symptoms of salt wasting. By means of haplotype analysis linkage was shown to the MCKD1 locus (logarithm of the odds score, 3.34). CONCLUSION: Establishing a diagnosis of MCKD solely on clinical findings is difficult because signs and symptoms may be subtle, renal cysts may be absent in more than 50% of affected individuals, and renal histological abnormalities are nonspecific. In patients presenting with renal insufficiency from apparent interstitial disease, a thorough family history and genetic linkage studies are required to establish a diagnosis of MCKD. We suspect MCKD is underdiagnosed and the true incidence of MCKD1 in the general population may be underestimated. No further living-related transplantation should be performed until genetic testing can exclude potentially affected donors.
BACKGROUND: Autosomal dominant medullary cystic kidney disease type 1 (MCKD1; Mendelian Inheritance in Man 174000) is a hereditary tubulointerstitial renal disease. For MCKD1, a locus on chromosome 1q21 is published. Although there are characteristic biopsy and imaging findings for MCKD, clinical diagnosis of this disorder is still very difficult because unique phenotypic features are not always present in individual cases. METHODS: In a large Native-American kindred with apparent autosomal dominant nephropathy, clinical findings in more than 50 individuals were collected and evaluated. Haplotype analysis for 34 individuals was performed. RESULTS: We report the difficulties establishing the diagnosis of MCKD in a large Native-American kindred solely by means of clinical criteria. This kindred shows a wider range of age of disease onset than previously reported. Gout and hypertension were common, but no patient reported symptoms of salt wasting. By means of haplotype analysis linkage was shown to the MCKD1 locus (logarithm of the odds score, 3.34). CONCLUSION: Establishing a diagnosis of MCKD solely on clinical findings is difficult because signs and symptoms may be subtle, renal cysts may be absent in more than 50% of affected individuals, and renal histological abnormalities are nonspecific. In patients presenting with renal insufficiency from apparent interstitial disease, a thorough family history and genetic linkage studies are required to establish a diagnosis of MCKD. We suspect MCKD is underdiagnosed and the true incidence of MCKD1 in the general population may be underestimated. No further living-related transplantation should be performed until genetic testing can exclude potentially affected donors.
Authors: Matthias T F Wolf; Bettina E Mucha; Hans C Hennies; Massimo Attanasio; Franziska Panther; Isabella Zalewski; Stephanie M Karle; Edgar A Otto; C Constantinou Deltas; Arno Fuchshuber; Friedhelm Hildebrandt Journal: Hum Genet Date: 2006-04-26 Impact factor: 4.132
Authors: Anthony J Bleyer; Stanislav Kmoch; Corinne Antignac; Vicki Robins; Kendrah Kidd; John R Kelsoe; Gerald Hladik; Philip Klemmer; Stephen J Knohl; Steven J Scheinman; Nam Vo; Ann Santi; Alese Harris; Omar Canaday; Nelson Weller; Peter J Hulick; Kristen Vogel; Frederick F Rahbari-Oskoui; Jennifer Tuazon; Constantinos Deltas; Douglas Somers; Andre Megarbane; Paul L Kimmel; C John Sperati; Avi Orr-Urtreger; Shay Ben-Shachar; David A Waugh; Stella McGinn; Anthony J Bleyer; Katerina Hodanová; Petr Vylet'al; Martina Živná; Thomas C Hart; P Suzanne Hart Journal: Clin J Am Soc Nephrol Date: 2014-02-07 Impact factor: 8.237
Authors: Jan M Williams; Ashley C Johnson; Cary Stelloh; Albert W Dreisbach; Nora Franceschini; Kevin R Regner; Raymond R Townsend; Richard J Roman; Michael R Garrett Journal: Hypertension Date: 2012-09-17 Impact factor: 10.190