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Familial hypomagnesemia-hypercalciuria in 2 siblings
E Kuwertz-Bröking1, S Fründ, M Bulla
1Department of Pediatrics, University Children's Hospital, University of Münster, Germany.
Insights
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is a rare genetic kidney disease. A mutation in the paracellin-1 gene caused severe renal issues in two siblings, unresponsive to magnesium therapy.
Area of Science:
- Pediatric Nephrology
- Medical Genetics
Background:
- Familial hypomagnesemia-hypercalciuria with nephrocalcinosis and renal insufficiency in childhood is a rare genetic disorder.
- This condition is characterized by renal calcium and magnesium wasting, leading to nephrocalcinosis and kidney dysfunction.
Observation:
- Two siblings from consanguineous parents presented with severe renal insufficiency and bilateral nephrocalcinosis.
- Biochemical analyses revealed hypomagnesemia, hypercalciuria, tubular and glomerular proteinuria, and low urinary citrate excretion.
- Kidney histology in the more severely affected boy showed medullary nephrocalcinosis, tubular atrophy, fibrosis, and glomerulosclerosis.
Findings:
- Genetic analysis identified a homozygous frameshift mutation in the paracellin-1 gene in both affected siblings.
- Treatment with sodium bicarbonate, vitamin D analogs, thiazide diuretics, citrate, and magnesium partially reduced hypercalciuria but did not correct hypomagnesemia.
- The boy progressed to hemodialysis, while his sister's renal function remained stable during follow-up.
Implications:
- This study highlights the critical role of paracellin-1 in renal magnesium and calcium transport.
- The findings underscore the genetic basis and variable clinical presentation of this rare kidney disease.
- Understanding the genetic defect and treatment response is crucial for managing patients with familial hypomagnesemia-hypercalciuria.
Abstract:
Familial hypomagnesemia-hypercalciuria with nephrocalcinosis and renal insufficiency in childhood is a rarely described disease. Two siblings of consanguineous Tunesian parents (first cousins), a 2-year-old boy and a 4-year-old girl presented with renal insufficiency and severe bilateral nephrocalcinosis. Both were found to have decreased serum and intracellular magnesium concentrations, increased urinary excretion of magnesium and calcium, mild glomerular and severe tubular proteinuria and low citrate excretion in urine. Pathological biochemical findings and the severity of nephrocalcinosis of the boy compared to findings of the sister were strongly marked, Histology of the boy's kidney showed severe medullary nephrocalcinosis, tubular atrophy, focal lymphoplasmacellulary infiltration, focal cortical fibrosis, immature glomerula, segmental and global glomerulosclerosis. Subsequent mutation analysis revealed a homozygous frameshift mutation in the gene paracellin-1 in both affected individuals. Therapy consisted of sodium bicarbonate, cholecalciferol, calcitriol, hydrochlorothiazide, citrate salts and oral magnesium administration. Hypercalciuria decreased in both children by therapy with thiazide diuretics, but hypomagnesemia was unresponsive to magnesium administration. After a 32-month follow-up the boy commenced hemodialysis at the age of 5 years, whereas his sister showed no decline in renal function.