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Heterogeneity is a common ground in familial hypomagnesemia with hypercalciuria and nephrocalcinosis caused by CLDN19 gene mutations.
Vall-Palomar, Mònica; Burballa, Carla; Claverie-Martín, Félix; Meseguer, Anna; Ariceta, Gema.
Affiliation
  • Vall-Palomar M; Fisiopatologia Renal, Centre D'Investigacions en Bioquímica I Biologia Molecular (CIBBIM), Institut de Recerca Vall D'Hebron (VHIR), Barcelona, Spain.
  • Burballa C; Fisiopatologia Renal, Centre D'Investigacions en Bioquímica I Biologia Molecular (CIBBIM), Institut de Recerca Vall D'Hebron (VHIR), Barcelona, Spain.
  • Claverie-Martín F; Unidad de Investigación, Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.
  • Meseguer A; Fisiopatologia Renal, Centre D'Investigacions en Bioquímica I Biologia Molecular (CIBBIM), Institut de Recerca Vall D'Hebron (VHIR), Barcelona, Spain.
  • Ariceta G; Departament de Bioquímica I Biologia Molecular. Unitat de Bioquímica de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
J Nephrol ; 34(6): 2053-2062, 2021 Dec.
Article in En | MEDLINE | ID: mdl-33929692
ABSTRACT

BACKGROUND:

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare tubulopathy caused by mutations in the CLDN16 or CLDN19 genes. Patients usually develop hypomagnesemia, hypercalciuria, nephrocalcinosis and renal failure early in life. Patients with CLDN19 mutations may also have ocular abnormalities. Despite clinical variability, factors associated with kidney function impairment, especially in patients with CLDN19 mutations, have not been addressed.

METHODS:

Retrospective multicenter study of 30 genetically confirmed FHHNC Spanish patients. We analyzed kidney function impairment considering as outcomes chronic kidney disease (CKD) stage 3 and annual estimated glomerular filtration rate (eGFR) decline, to identify factors associated with the different phenotypes.

RESULTS:

Of thirty patients, 27 had mutations in the CLDN19 gene (20 homozygous for the p.G20D mutation) and 3 in the CLDN16. Age at diagnosis was 1.71 (0.67-6.04) years and follow-up time was 8.34 ± 4.30 years. No differences in CKD stage 3-free survival based on CLDN19 mutation (p.G20D homozygous vs. other mutations) or gender were found, although females seemed to progress faster than males. Patients with more pronounced eGFR decline had higher PTH levels at diagnosis than those with stable kidney function, despite similar initial eGFR. Approximately 60% of CLDN19 patients presented ocular abnormalities. Furthermore, we confirmed high phenotypic intrafamilial variability.

CONCLUSIONS:

In a contemporary cohort of FHHNC patients with CLDN19 mutations, females seemed to progress to CKD-stage 3 faster than males. Increased PTH levels at baseline may indicate a more severe renal course. There was high phenotype variability among patients with CLDN19 mutations and kidney function impairment  differed even between siblings.
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Full text: 1 Database: MEDLINE Main subject: Nephrocalcinosis Type of study: Diagnostic_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Female / Humans / Male Language: En Year: 2021 Type: Article

Full text: 1 Database: MEDLINE Main subject: Nephrocalcinosis Type of study: Diagnostic_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Female / Humans / Male Language: En Year: 2021 Type: Article