CEDIE   05498
CENTRO DE INVESTIGACIONES ENDOCRINOLOGICAS "DR. CESAR BERGADA"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis (FHHNC) Due a Mutation in CLDN19
Autor/es:
LIERN, MIGUEL; BERGADÁ, IGNACIO; MASNATA, MARÌA EUGENIA; VELLEJOS, GRACIELA; KONRAD, MARTIN; FREIRE, ANALIA
Lugar:
Buenos Aires
Reunión:
Congreso; XXVI Reunion Anual de la Sociedad Latinoamericana de Endocrinología Pediatrica; 2016
Resumen:
Background: FHHNC is an autosomal recessive renal diseasecharacterized by calcium and magnesium wasting. It is caused bymutations in the CLDN16 and CLDN19 genes that encode the tightjunction proteins claudin-16 or claudin-19, respectively. Patientsexhibit nephrocalcinosis (NC) and progression to renal failure.The aim of this report is to describe two siblings affected by thisrare disease due to a mutation in CLDN19, whose diagnosis wasconfirmed by specific molecular analysis.Case Report:Case 1: A 7 year-old boy with a history of recurrent abdominalpain; he was referred after detection of nephrocalcinosis (NC) inabdominal x-ray and renal ultrasound. Laboratory analysis revealed:mild increment on iPTH (72 pg/mL), elevated serum creatinine,(Barrat Index 88 mL/min/m2), nomal 25OHVit D, hyperuricemia,normal serum Ca+ and PO4? but normal to low serumMg++. He presented hypercalciuria, microalbuminuria and hypocitraturiain 24-hour urine sample. Ultrasound and TC 99 Smibiscintigraphy of parathyroid glands were normal.Case 2: A 2 year-old asymptomatic girl; NC by ultrasound wasdetected by family screening. She presented elevated serum iPTH(189 pg/mL) and similar urine findings as her brother.Fractional Magnesium Excretion calculated (FEMg++) in bothwere 8.9 and 10.45% (NV: A, p.Gly20Asp) of the CLDN19gene (1p34.2) in both siblingsthat has been described as the classical Hispanic founder mutation.Although there is no specific treatment for this disease, treatmentwith thiazide diuretics was introduced to reduce calciuriaand potassium citrate to prevent renal failure progression. Sixmonths after onset of treatment, both patients achieved normalcalciuria and stable kidney function.Conclusion: In FHHNC, the PTH increment is characteristicbut not related to a primary disorder of the parathyroid gland.FEMg++ was essential to establish the diagnosis and genetic confirmation.The early diagnosis and implementation of specific treatmentcould modify renal failure progression in those patients andenhance their quality of life.