Familial hypomagnesemia with hypercalciuria and nephrocalcinosis

Praga, Manuel; Vara, Julia; Gonzlez-Parra, Emilio; Andrs, Amado; Alamo, C; Araque, Alfonso; Oritz, A; Rodicio, J. L.

doi:10.1007/bf00862058

Cited by 32 publications

(88 citation statements)

References 5 publications

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“…Extrarenal features were absent. These data are consistent with previous reports, and heterozygous mutations of CLDN19 and CLDN16 are now recognized as risk factors for hypercalciuria and kidney stones (5,10,15). Although a common polymorphism in the CLDN14 gene has been associated with the occurrence of kidney stones and increased urinary Ca 2ϩ levels (17), the role of CLDN16 and CLDN19 polymorphisms in hypercalciuria and/or kidney stones in the general population is unknown and remain to be assessed.…”

Section: Discussionsupporting

confidence: 90%

“…In this series, blood and urinary tests confirmed the usual features of FHHNC (15) in CLDN19 patients: (1) persistent hypomagnesemia unresponsive to Mg 2ϩ administration, (2) thiazide-sensitive hypercalciuria with normal serum Ca 2ϩ levels and a slightly increased parathormone level, (3) low urinary citrate excretion, and (4) progressive renal failure leading to ESRD. However, one can note some peculiar renal findings.…”

Section: Discussionsupporting

confidence: 73%

“…Because of the recent recognition of CLDN19 mutations in humans and their low frequency, this analysis has not yet been performed in patients with CLDN19 mutations. Second, in patient F2.3, calciuria returned to normal values after 1 year of thiazide-diuretic intake, which is an unusual finding (15). Serum Mg 2ϩ level was not modified.…”

Section: Discussionmentioning

confidence: 76%

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Renal, Ocular, and Neuromuscular Involvements in Patients with CLDN19 Mutations

Faguer¹,

Chauveau²,

Pascal³

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives The objective of this study was to describe the renal and extrarenal findings in patients with recessively inherited familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) associated with CLDN19 mutations.Design, setting, participants, & measurements Medical records of three patients from two French unrelated families with CLDN19 mutations were retrospectively examined.Results Direct sequencing of CLDN19 identified a known variant (p.Gly20Asp) in all patients and a new missense mutation (p.Val44Met) in one (compound heterozygous). The patients' renal phenotype closely mimicked CLDN16-related nephropathy: low serum Mg 2ϩ (Ͻ0.65 mmol/L) despite oral supplementation, hypercalciuria partly thiazide-sensitive, and progressive renal decline with ESRD reached at age 16 and 22 years in two individuals. Primary characteristics (failure to thrive, recurrent urinary tract infections, or abdominal pain), age at onset (0.8 to 16 years), and rate of renal decline were highly heterogeneous. Ocular involvement was identified in all patients, although two patients did not have visual loss. Additionally, exercise intolerance with pain, weakness, and electromyographical alterations mimicking a Ca 2ϩ /K ϩ channelopathy (pattern V) were observed in two of three individuals. These features persisted despite the normalization of serum K ϩ and Mg 2ϩ after renal transplantation.Conclusions Ocular manifestations, even subtle, and exercise intolerance mimicking mild to moderate periodic paralysis are two symptoms that need to be searched for in patients with FHHNC and may indicate CLDN19 mutations.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 73%

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Renal, Ocular, and Neuromuscular Involvements in Patients with CLDN19 Mutations

Faguer¹,

Chauveau²,

Pascal³

et al. 2011

Clinical Journal of the American Society of Nephrology

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“…3,[5][6][7][8] Unlike most other inherited tubular diseases affecting electrolyte homeostasis, FHHNC is generally complicated by progressive renal failure during childhood or adolescence, but the pathogenesis of chronic renal failure remains a matter of debate.…”

mentioning

confidence: 99%

“…2,10 -13 Hypercalciuria and nephrolithiasis have also been observed in heterozygous FHHNC mutation carriers. 2,3 FHHNC is a genetically heterogeneous disease because recently CLDN19 mutations have been identified in a cohort of patients mainly originating from Spain. 14 The renal phenotype of these patients is very similar to patients exhibiting CLDN16 mutations; however, patients with CLDN19 mutations also have severe ocular abnormalities in most cases.…”

mentioning

confidence: 99%

CLDN16 Genotype Predicts Renal Decline in Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis

Konrad¹,

Hou

Weber

et al. 2008

Journal of the American Society of Nephrology

115

130

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Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive tubular disorder caused by CLDN16 mutations. CLDN16 encodes the renal tight junction protein claudin-16, which is important for the paracellular reabsorption of calcium and magnesium in the thick ascending limb of Henle's loop. That FHHNC is frequently associated with progressive renal failure suggests additional roles for claudin-16 in the maintenance of tight junction integrity. An investigation of 32 patients with FHHNC and 17 different mutations was previously reported; here, the analysis is expanded to 39 additional patients and 12 new mutations. Expression studies revealed that five of the 12 new mutations led to partial loss of claudin-16 function and the remaining seven led to complete loss of function. The 23 patients who had mutations resulting in complete loss of function of both alleles were significantly younger at the onset of symptoms than the 46 patients who had at least one mutant allele providing partial function (2.2 versus 5.6 years; P Ͻ 0.01). In addition, those with complete loss of function had a more rapid decline in GFR (7.3 versus 2.9 ml/min per 1.72 m 2 /y; P Ͻ 0.01), leading to 54% requiring renal replacement therapy by age 15 compared with 20% of those with residual function (P Ͻ 0.05). These data suggest that residual function of claudin-16 may delay the progression of renal failure in FHHNC.

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The role of the papilla in idiopathic calcium oxalate nephrolithiasis

Krautschick

Esen

1997

World J Urol

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The complex and multifactorial phenomenon of urinary stone disease remains unclear. Anatomical and physiochemical theories do not adequately deal with certain aspects of idiopathic calcium oxalate nephrolithiasis in particular or of nephrolithiasis. One of the reasons for this could be that nephrolithiasis is not only a primary disorder but may also be a symptom of other disorders or various pathologic changes in the metabolism of lithogenic substances. Both affirmative and contradictory reports have been published since Randall's first description of papillary calcifications and their possible active role in the genesis of calcium oxalate nephrolithiasis. Our intention is to discuss focal calcified lesions as an etiologic factor of renal stone disease as well as the change from historical to modern concepts regarding the development of medullary calcifications and their relationship to idiopathic calcium oxalate nephrolithiasis.

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Familial hypomagnesemia with hypercalciuria and nephrocalcinosis

Cited by 32 publications

References 5 publications

Renal, Ocular, and Neuromuscular Involvements in Patients with CLDN19 Mutations

Renal, Ocular, and Neuromuscular Involvements in Patients with CLDN19 Mutations

CLDN16 Genotype Predicts Renal Decline in Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis

The role of the papilla in idiopathic calcium oxalate nephrolithiasis

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