Discordant Clinical Course of Vitamin-D-Hydroxylase (CYP24A1) Associated Hypercalcemia in Two Adult Brothers With Nephrocalcinosis

Background/Aims: Hypercalcemia can result in nephrocalcinosis/nephrolithiasis and may lead to renal failure. Idiopathic infantile hypercalcemia is caused by mutations of the CYP24A1 gene, which regulates vitamin D activity. Classically infants present with hypercalcemia. Recently, a number of indivi...

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Main Authors: Tilman Jobst-Schwan, Andrea Pannes, Karl Peter Schlingmann, Kai-Uwe Eckardt, Bodo B. Beck, Michael S. Wiesener
Format: Article
Language:English
Published: Karger Publishers 2015-08-01
Series:Kidney & Blood Pressure Research
Subjects:
Online Access:http://www.karger.com/Article/FullText/368520
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spelling doaj-52c026b9250845ca8de1cc2e98eab0622020-11-25T03:41:35ZengKarger PublishersKidney & Blood Pressure Research1420-40961423-01432015-08-0140544345110.1159/000368520368520Discordant Clinical Course of Vitamin-D-Hydroxylase (CYP24A1) Associated Hypercalcemia in Two Adult Brothers With NephrocalcinosisTilman Jobst-SchwanAndrea PannesKarl Peter SchlingmannKai-Uwe EckardtBodo B. BeckMichael S. WiesenerBackground/Aims: Hypercalcemia can result in nephrocalcinosis/nephrolithiasis and may lead to renal failure. Idiopathic infantile hypercalcemia is caused by mutations of the CYP24A1 gene, which regulates vitamin D activity. Classically infants present with hypercalcemia. Recently, a number of individuals have been reported with late onset clinical manifestation or late diagnosis in adulthood. All these patients are believed to show hypercalciuria. Methods: We report a 24 year old patient of healthy consanguine parents. Genetic analysis was performed by Sanger sequencing of the CYP24A1 gene in the index patient and targeted exon 2 analysis of all other family members. Results: The patient was hospitalized with severe malaise during an acute EBV-infection. He showed hypercalcemia > 3mmol/l and acute, hypovolemic renal failure with profound nephrocalcinosis, but no hypercalciuria. Genetic workup revealed a homozygous loss-of-function mutation p.E143del in the CYP24A1 gene. His clinically asymptomatic brother showed nephrocalcinosis of lesser degree. Repeatedly, low parathyroid hormone levels were detected in both brothers. Conclusion: This family displays the highly variable phenotype of CYP24A1 biallelic mutation carriers. CYP24A1 associated disease is an important differential diagnosis for the workup and counseling of infants as well as adults with hypercalcemia since a proper genetic diagnosis may result in therapeutic consequences.http://www.karger.com/Article/FullText/368520Calcium metabolismHypercalciuriaNephrolithiasisKidney stonesHypervitaminosis
collection DOAJ
language English
format Article
sources DOAJ
author Tilman Jobst-Schwan
Andrea Pannes
Karl Peter Schlingmann
Kai-Uwe Eckardt
Bodo B. Beck
Michael S. Wiesener
spellingShingle Tilman Jobst-Schwan
Andrea Pannes
Karl Peter Schlingmann
Kai-Uwe Eckardt
Bodo B. Beck
Michael S. Wiesener
Discordant Clinical Course of Vitamin-D-Hydroxylase (CYP24A1) Associated Hypercalcemia in Two Adult Brothers With Nephrocalcinosis
Kidney & Blood Pressure Research
Calcium metabolism
Hypercalciuria
Nephrolithiasis
Kidney stones
Hypervitaminosis
author_facet Tilman Jobst-Schwan
Andrea Pannes
Karl Peter Schlingmann
Kai-Uwe Eckardt
Bodo B. Beck
Michael S. Wiesener
author_sort Tilman Jobst-Schwan
title Discordant Clinical Course of Vitamin-D-Hydroxylase (CYP24A1) Associated Hypercalcemia in Two Adult Brothers With Nephrocalcinosis
title_short Discordant Clinical Course of Vitamin-D-Hydroxylase (CYP24A1) Associated Hypercalcemia in Two Adult Brothers With Nephrocalcinosis
title_full Discordant Clinical Course of Vitamin-D-Hydroxylase (CYP24A1) Associated Hypercalcemia in Two Adult Brothers With Nephrocalcinosis
title_fullStr Discordant Clinical Course of Vitamin-D-Hydroxylase (CYP24A1) Associated Hypercalcemia in Two Adult Brothers With Nephrocalcinosis
title_full_unstemmed Discordant Clinical Course of Vitamin-D-Hydroxylase (CYP24A1) Associated Hypercalcemia in Two Adult Brothers With Nephrocalcinosis
title_sort discordant clinical course of vitamin-d-hydroxylase (cyp24a1) associated hypercalcemia in two adult brothers with nephrocalcinosis
publisher Karger Publishers
series Kidney & Blood Pressure Research
issn 1420-4096
1423-0143
publishDate 2015-08-01
description Background/Aims: Hypercalcemia can result in nephrocalcinosis/nephrolithiasis and may lead to renal failure. Idiopathic infantile hypercalcemia is caused by mutations of the CYP24A1 gene, which regulates vitamin D activity. Classically infants present with hypercalcemia. Recently, a number of individuals have been reported with late onset clinical manifestation or late diagnosis in adulthood. All these patients are believed to show hypercalciuria. Methods: We report a 24 year old patient of healthy consanguine parents. Genetic analysis was performed by Sanger sequencing of the CYP24A1 gene in the index patient and targeted exon 2 analysis of all other family members. Results: The patient was hospitalized with severe malaise during an acute EBV-infection. He showed hypercalcemia > 3mmol/l and acute, hypovolemic renal failure with profound nephrocalcinosis, but no hypercalciuria. Genetic workup revealed a homozygous loss-of-function mutation p.E143del in the CYP24A1 gene. His clinically asymptomatic brother showed nephrocalcinosis of lesser degree. Repeatedly, low parathyroid hormone levels were detected in both brothers. Conclusion: This family displays the highly variable phenotype of CYP24A1 biallelic mutation carriers. CYP24A1 associated disease is an important differential diagnosis for the workup and counseling of infants as well as adults with hypercalcemia since a proper genetic diagnosis may result in therapeutic consequences.
topic Calcium metabolism
Hypercalciuria
Nephrolithiasis
Kidney stones
Hypervitaminosis
url http://www.karger.com/Article/FullText/368520
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