Hypomagnesemia with hypercalciuria and nephrocalcinosis with ocular involvement

FHHNC with ocular involvement is an autosomal recessive disorder with hypomagnesemia, hypercalciuria, nephrocalcinosis and coloboma often complicated by progressive chronic renal failure during childhood or adolescence. Loss of function mutations in the CLDN19 gene are the underlying genetic cause.

Historical Aspects

The first family as described by Michelis 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. Ocular symptoms are pathognomonic of this disorder, and findings are myopia, nystagmus and chorioretinitis. Other organ's involvement includes tetany, seizures, hypertension, gout, deafness, chondrocalcinosis, and rickets.

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 CLDN19.

Management

It is only a symptomatic therapy available for this disorder, which includes substitution of renal mineral losses, 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 and ocular symptoms.

Systematic

Hypomagnesemia
	EGFR
	Gitelman syndrome
	Hereditary myokymia type 1
	Hypomagnesemia with hypercalciuria and nephrocalcinosis
	Hypomagnesemia with hypercalciuria and nephrocalcinosis with ocular involvement
		CLDN19
	Hypomagnesemia with normocalciuria
	Intestinal hypomagnesemia with secondary hypocalcemia
	Isolated dominant hypomagnesemia
	Renal cysts and diabetes (RCAD)
	Renal hypomagnesemia 6
	TRPM7