Hypomagnesaemia–hypercalciuria–nephrocalcinosis: a report of nine cases and a review

Benigno, Vincenzo; Canonica, Claudia; Bettinelli, Alberto; Vigier, Rodo O. von; Truttmann, Anita C.; Bianchetti, Mario G.

doi:10.1093/ndt/15.5.605

Cited by 79 publications

(70 citation statements)

References 28 publications

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“…No difference in renal phenotype between patients with mutations in these two genes has yet been described. By contrast, severe ocular involvement (macular coloboma, pigmentary retinitis, nystagmus, or visual loss) has been described in CLDN19 patients, whereas only mild nonspecific ocular involvement (myopia, astigmatism, hypermetropia, or strabismus) has been reported in some CLDN16 patients (3,6,8).…”

Section: Introductionmentioning

confidence: 97%

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Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis

Godron¹,

Harambat²,

Boccio³

et al. 2012

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is a rare autosomal recessive renal tubular disease. It is caused by mutations in CLDN16 and CLDN19, encoding claudin-16 and -19, respectively. Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is usually complicated by progressive CKD. The objectives of this study were to describe the clinical and genetic features of familial hypomagnesemia with hypercalciuria and nephrocalcinosis and analyze phenotype-genotype associations in patients with CLDN16 or CLDN19 mutations.Design, setting, participants, & measurements Data from 32 genetically confirmed patients (9 patients with CLDN16 and 23 patients with CLDN19 mutations) from 26 unrelated families were retrospectively reviewed.Results Diagnosis was based on clinical criteria at a median age of 9.5 years and confirmed by genetic testing at a median age of 15.5 years. In total, 13 CLDN16 or CLDN19 mutations were identified, including 8 novel mutations. A founder effect was detected for the recurrent CLDN16 p.Ala139Val mutation in North African families and the CLDN19 p.Gly20Asp mutation in Spanish and French families. CKD was more frequently observed in patients with CLDN19 mutations: survival without CKD or ESRD was 56% at 20 years of age in CLDN19 versus 100% in CLDN16 mutations (log rank P,0.01). Ocular abnormalities were observed in 91% of patients with CLDN19 mutations and none of the patients with CLDN16 mutations (P,0.01). Treatments seem to have no effect on hypercalciuria and CKD progression.Conclusions Patients with CLDN19 mutations may display more severe renal impairment than patients with CLDN16 mutations. Ocular abnormalities were observed only in patients with CLDN19 mutations.

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Section: Introductionmentioning

confidence: 97%

“…Only 87 patients (51 families) have been described to date in international publications (2,3). It is caused by mutations in the CLDN16 and CLDN19 genes, encoding claudin-16 and -19 (4,5).…”

Section: Introductionmentioning

confidence: 99%

Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis

Godron¹,

Harambat²,

Boccio³

et al. 2012

Clinical Journal of the American Society of Nephrology

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“…It encompasses renal Mg 2ϩ and Ca 2ϩ wasting, leading to hypomagnesemia, nephrocalcinosis, and progressive renal decline. FHHNC may be disclosed by a wide variety of symptoms, including recurrent urinary tract infection, polyuria and/or polydipsia, nephrolithiasis, or tetanic convulsions (11). In patients with CLDN16 mutations, progression to ESRD may be predicted by the genotype (12).…”

Section: Introductionmentioning

confidence: 99%

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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“…Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC; OMIM 248250) is an autosomal recessive renal disorder characterized by excessive renal Mg 2+ wasting, resulting in persistent hypomagnesemia, renal Ca 2+ wasting, bilateral nephrocalcinosis, and progressive renal failure [3][4][5][6]. Symptoms usually begin in the first few months of life.…”

Section: Familial Hypomagnesemia With Hypercalciuria and Nephrocalcinmentioning

confidence: 99%

“…Hyperuricemia is observed in the majority of patients [3,9,10]. Ocular abnormalities (severe myopia, nystagmus and chorioretinitis) and hearing impairment have been reported as inconsistent extrarenal symptoms in FHHNC [6].…”

Section: Familial Hypomagnesemia With Hypercalciuria and Nephrocalcinmentioning

confidence: 99%

Inherited forms of renal hypomagnesemia: an update

Knoers

2009

Pediatr Nephrol

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The kidney plays an important role in ion homeostasis in the human body. Several hereditary disorders characterized by perturbations in renal magnesium reabsorption leading to hypomagnesemia have been described over the past 50 years, with the most important of these being Gitelman syndrome, familial hypomagnesemia with hypercalciuria and nephrocalcinosis, familial hypomagnesemia with secondary hypocalcemia, autosomal dominant hypomagnesemia with hypocalciuria, and autosomal recessive hypomagnesemia. Only recently, following positional cloning strategies in affected families, have mutations in renal ion channels and transporters been identified in these diseases. In this short review, I give an update on these hypomagnesemic disorders. Elucidation of the genetic etiology and, for most of these disorders, also the underlying pathophysiology of the disease, has greatly increased our understanding of the normal physiology of renal magnesium handling. This is yet another example of the importance of studying rare disorders in order to unravel physiological and pathophysiological processes in the human body. are not yet clear. Hypomagnesemia is a common finding in hospitalized patients and often an acquired disorder resulting from deficient oral intake or accelerated urinary or intestinal loss. Acquired renal magnesium wasting is commonly caused by Pediatr Nephrol (2009) 24:697-705

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Hypomagnesaemia–hypercalciuria–nephrocalcinosis: a report of nine cases and a review

Abstract: The results indicate an autosomal recessive inheritance. The diagnosis of primary hypomagnesaemia-hypercalciuria-nephrocalcinosis deserves consideration in any patient with nephrocalcinosis and hypercalciuria.

Cited by 79 publications

References 28 publications

Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis

Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis

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

Inherited forms of renal hypomagnesemia: an update

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