Clinical feature: 

Definition: 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.

History: The first family as described by Michelis exhibited renal magnesium wasting and a distal renal tubular acidosis.

Clinical picture: 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.
   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.

Diagnostics: 

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.  » » » 

Differential: The most important differential is the cousin disorder without ocular findings that closely resembles as it is caused by the same pathogenetic mechanism.  » » » 
   Patients with hypomagnesemia and secondary hypocalcemia have normal renal calcium excretion. Their hypocalcemia is treated with magnesium supplemetation, but does not respond well to calcium or vitamin D supplementation.  » » » 
   Isolated hypomagnesemias (IDH/IRH) go without hypocalcemia and hypercalciuria.  » » » 

Literature: 

Vezzoli G et al. (2008) Hypercalciuria revisited: one or many conditions?
Hou J et al. (2008) Claudin-16 and claudin-19 interact and form a cation-selective tight junction complex.
Vezzoli G et al. (2008) Update on primary hypercalciuria from a genetic perspective.
Alexander RT et al. (2008) Molecular determinants of magnesium homeostasis: insights from human disease.
Günzel D et al. (2009) Function and regulation of claudins in the thick ascending limb of Henle.
Michelis MF et al. (1972) Decreased bicarbonate threshold and renal magnesium wasting in a sibship with distal renal tubular acidosis. (Evaluation of the pathophysiological role of parathyroid hormone).