Hypomagnesemia with hypercalciuria and nephrocalcinosis

FHHNC without ocular involvement is an autosomal recessive disorder with hypomagnesemia, hypercalciuria and nephrocalcinosis often complicated by progressive chronic renal failure during childhood or adolescence. Loss of function mutations in the CLDN16 gene are the underlying genetic cause.

Historical Aspects

The first family as described by Michelis in 1972 exhibited renal magnesium wasting and a distal renal tubular acidosis.[Error: Macro 'ref' doesn't exist]

Clinical Findings

Signs and Symptoms

The first typical symptom is nephrocalcinosis, which becomes apparent in childhood or adolescence. if not a sibling is affected or consanguinity present family history is not instructice as with all recessive disorders. Although the prevailing symptoms are renal and every so often end-stage renal failure develops, it is an multiorgan disorder. Symptoms include tetany, seizures, hypertension, gout, deafness, chondrocalcinosis, and rickets. if ocular symptoms present, the cousin disorder FHHNC with ocular abnormalities should be considered.

Laboratory Findings

Plasma magnesium is 0.59 ± 0.06 mmol/l. Renal magnesium excretion is inaprpriatly high 2.07 ± 0.073mmol/d. The same holds true for fractional magnesium excretion 12.5 ± 4.7%. Of note, trenal calcium excretion is also elevated. Urinary calcium creatinin ratio is 1.88 ± 0.67.

Diagnosis

Often the patients present with urinary tract infections and carful sultrasound examination then reveals nephrocalcinosis. The diagnosis is further confirmed by laboratory findings and finally proved by molecular genetic tests of CLDN16.

Management

It is only a symptomatic therapy available for this disorder, which includes substitution of renal mineral losses, urinary dilution by increase water intake, the complex care for recurrent kidney stones, and antibiotics if urinary tract infections occur. Unfortunately these measures exert minimal effect on the progression of renal failure, so the ultimate therapie is a renal transplant after which the disease is definitely cured.

Systematic

Hypomagnesemia
	EGFR
	Gitelman syndrome
	Hereditary myokymia type 1
	Hypomagnesemia with hypercalciuria and nephrocalcinosis
		CLDN16
	Hypomagnesemia with hypercalciuria and nephrocalcinosis with ocular involvement
	Hypomagnesemia with normocalciuria
	Intestinal hypomagnesemia with secondary hypocalcemia
	Isolated dominant hypomagnesemia
	Renal cysts and diabetes (RCAD)
	Renal hypomagnesemia 6
	TRPM7