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The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
Orpha Number: 34528
A mild form of familial primary hypomagnesemia (FPH), characterized by extreme weakness, tetany and convulsions. Secondary disturbances in calcium excretion are observed.
To date, only one large pedigree with 18 affected individuals has been reported in the literature.
Autosomal dominant primary hypomagnesemia with hypocalciuria (ADPHH) can be detected in childhood or in adult life. Most affected individuals are asymptomatic but patients may suffer from generalized convulsions. In adulthood, chondrocalcinosis may be observed.
ADPHH is caused by mutations in the FXYD2 gene (11q23; mutation p.Gly41Arg) which encodes the gamma subunit of the Na+/K+-ATPase, localized on the basolateral membranes of nephron epithelial cells and expressed in the distal convoluted tubule. A similar phenotype is observed in about 45-65% of patients with mutations in the HNF1B gene (hepatocyte nuclear factor 1B; 17q12), which encodes a transcription factor expressed in renal epithelia. Indeed, this transcription factor stimulates transcriptional expression of the FXYD2 gene. Hypokalemia is observed in 46% of patients with HNF1B gene mutations.
Diagnosis relies on a hypomagnesemia, hypermagnesuria and hypocalciuria phenotype. In patients with FXYD2 mutations, no hypokalemia or metabolic alkalosis is observed. In contrast, in patients with HNF1B mutations, hypokalemia can be detected. Diagnosis is confirmed by the genetic screening of the genes FXYD2 and HNF1B.
Differential diagnosis includes all causes of renal hypomagnesemia, particularly diseases associated with hypocalciuria such as Gitelman syndrome, EAST syndrome and familial primary hypomagnesemia with normocalciuria and normocalcemia (see these terms).
Prenatal diagnosis relies on detection of bilateral hyperechogenic kidneys of normal or moderately enlarged size by ultrasound in patients with HNF1B mutations.
Transmission is autosomal dominant. Genetic counseling may be proposed and the recurrence risk is 50%.
Management and treatment
Management is mainly symptomatic and includes oral magnesium supplements.
Visit the Orphanet disease page for more resources.
Source: GARD Last updated on 05-01-20
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