Novel Insights from Clinical Practice

An Unusual Patient with Hypercalciuria, Recurrent Nephrolithiasis, Hypomagnesemia and G227R Mutation of Paracellin-1
An Unusual Patient with Hypercalciuria and Hypomagnesemia Unresponsive to Thiazide Diuretics
Faruk Kutluturk^a, Berna Temel^a, Bora Uslu^a, Ferihan Aral^a, Adil Azezli^a, Yusuf Orhan^a, Martin Konrad^b, Nese Ozbey<sup>a

a</sup>Department of Endocrinology and Metabolism, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey;
^bPediatric Nephrology, University Children's Hospital, Inselspital, Berne, Switzerland

Address of Corresponding Author

Horm Res 2006;66:175-181 (DOI: 10.1159/000094253)

  Key Words

• Hypercalciuria
• Hypomagnesemia
• Nephrolithiasis
• Paracellin-1
• Familial hypomagnesemia with hypercalciurial and nephrocalcinosis

  Abstract

A 19-year-old female patient with hypercalciuria and recurrent nephrolithiasis/urinary tract infection unresponsive to thiazide type diuretics is presented. The patient first experienced nephrolithiasis at the age of 4 years. Afterwards, recurrent passages of stones and urinary tract infection occurred. On diagnostic evaluation at the age of 19 years, she also had hypocitraturia and hypomagnesemia. Her serum calcium concentrations were near the lower limit of normal (8.5-8.8 mg/dl; normal range: 8.5-10.5), her serum magnesium concentrations were 1.15-1.24 mg/dl (normal range: 1.4-2.5) and urinary calcium excretion was 900 mg/24 h. PTH concentrations were increased (110-156 pg/ml; normal range: 10-65). We tried to treat the patient with hydrochlorothiazide at a dose of 50 mg/day. During treatment with thiazide diuretics, PTH concentration remained high and the patient had recurrent urinary tract infections and passages of stones. Serum magnesium concentration did not normalize even under the parenteral magnesium infusion. Her mother had a history of nephrolithiasis 20 years ago. Severe hypomagnesemia in association with hypercalciuria/urinary stones is reported as a rare autosomal recessive disorder caused by impaired reabsorption of magnesium and calcium in the thick assending limp of Henle's loop. Recent studies showed that mutations in the CLDN16 gene encoding paracellin-1 cause the disorder. In exon 4, a homozygous nucleotide exchange (G679C) was identified for the patient. This results in a point mutation at position Glycine227, which is replaced by an Arginine residue (G227R). The mother was heterozygous for this mutation. G227 is located in the fourth transmembrane domain and is highly conserved in the claudin gene family. This case indicates the pathogenetic role of paracellin-1 mutation in familial hypomagnesemia with hypercalciuria and nephrocalcinosis and further underlines the risk of stone formation in heterozygous mutation carriers.

Copyright © 2006 S. Karger AG, Basel

  Author Contacts

Faruk Kutluturk, MD
Department of Internal Medicine
Medical Faculty of Istanbul University, Capa, Fatih
TR-34015 Istanbul (Turkey)
Tel. +90 532 557 97 43, Tel./Fax +90 212 532 42 08, E-Mail fkutluturk@yahoo.com

  Article Information

Received: December 27, 2005
Accepted: May 15, 2006
Published online: June 27, 2006
Number of Print Pages : 7
Number of Figures : 2, Number of Tables : 1, Number of References : 27