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.
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]
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.
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.
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.
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.
Hypomagnesemia is a cardinal symptom of FHHNC without ocular involvement. Typical of this disorder is further hypocalcemia, due to excessive renal losses of divalent cations; nephrocalcinosis; recurrent kidney stones; and progressive renal failure.
Hypocalcemia is typical of FHHNC without ocular involvement though hypomagnesemia is essential. Other crucial symptoms are nephrocalcinosis, recurrent kidney stones, and progressive renal failure.
Nephrocalcinosis in FHHNC without ocular involvement is accompanied by hypomagnesemia and hypocalemia due to excessive renal losses. By contrast to other diseases with nephrocalcinosis, progressive renal failure is typical.
Hypercalciuria in FHHNC is accompanied by hypomagnesemia and nephrocalcinosis.
|Hereditary myokymia type 1|
|Hypomagnesemia with hypercalciuria and nephrocalcinosis|
|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|
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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).[^]
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Hampson G et al. (2008) Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC): compound heterozygous mutation in the claudin 16 (CLDN16) gene.[^]
OMIM.ORG articleOmim 248250 [^]