Familial hypomagnesemia with hypercalciuria and nefrocalcinosis (FHHNC)
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare condition in which there is an abnormality in the renal tubules due to which too much loss of magnesium and calcium in the urine occurs. The disease is caused by a mutation in the genetic material (DNA), in this case in the claudin 16 or 19 claudin gene. Claudine are transport proteins in the kidney tubules that make it possible to re-uptake salts and minerals from the urine. Claudine 16 and 19 are located in the loop of Henle, a specific part of the kidney tubule, where they enable the re-uptake of magnesium and calcium into the blood.
Signs and symptoms
Mutations in the genes claudin 16 or 19 interfere with the re-uptake of magnesium and calcium in the renal tubule, causing loss of magnesium and calcium in the urine. Although a reduced level of magnesium in the blood may cause different symptoms such as muscle weakness and muscle tremor / twitching, these are not prominently present in most patients with FHHNC. Patients with FHHNC usually present at a young age with urinary tract infections, thirst and excessive urination. Other common problems include the development of kidney stones and calcium deposits in the kidney (nephrocalcinosis). Patients with a mutation in claudin 19 genes may also cause serious eye diseases. Furthermore, most patients produce too much parathyroid hormone and most patients develop chronic renal failure due to calcium deposits in the kidney.
FHHNC is an inherited disease which is usually inherited autosomal recessive. This means that a person will get the disease when he or she has a claudin 16 or claudin 19 mutation in the genetic material from both father as mother. Because there are two mutations are needed, and the mutations are quite rare, the likelihood that children of patients with the disease have FHHNC is not large. Siblings of patients on the other hand do have a higher risk (25%) to also have FHHNC.
The diagnosis FHHNC is made on the basis of genetic research, in which two mutations in either the claudin 16 or 19 genes can be demonstrated.
The cause of FHHNC cannot be treated. In other words, the underlying problem (the deranged magnesium and calcium re-uptake) cannot be remedied.
The treatment, therefore, consists of the treatment of the mineral salt and disorders, and is directed to the prevention or treatment of symptoms and complications. Patients will have to take high doses of magnesium lifelong possibly in combination with drugs that reduce calcium excretion and / or reduce the risk of kidney stones and nephrocalcinosis.
FHHNC is a chronic condition, which means that it persists for life. The prognosis varies among patients. On average, one third of patients with FHHNC develop severe renal failure at the age of 15 years and ultimately need renal replacement therapy (dialysis, kidney transplantation).