ESPE Abstracts

Background: FHHNC is an autosomal recessive disorder caused by mutations in either claudin 19 or claudin 16. This is a rare disorder of magnesium metabolism with fewer than 400 reported cases throughout the literature. It is also a somewhat underdiagnosed disorder, not being commonly observed.

Case presentation: Patient was a 2 years old female who was incidentally noted to have nephrocalcinosis as part of evaluation for urinary tract infection. Her initial workup by renal service revealed elevated PTH, hence prompting a referral to endocrine.

Laboratory work-up: 25-OH vitamin D 37ng/ml (ref 30-100ng/ml), 1,25-OH vitamin D 57ng/ml (ref 31 – 87ng/ml), Alkaline phosphatase 215 U/L (ref 129 - 291 U/L), PTH 128 pg/ml (ref 9-59 pg/ml), Calcium 10.2 mg/dL (8.9 – 10.4mg/dL), Phosphorus 4.3mg/dL (3.1 – 6.3), Magnesium 1.6mg/dL (ref 1.5 – 2.4). Urine Calcium/Cr 0.6. Her PTH level remained elevated for her calcium level on multiple repeats. A Parathyroid scan did not reveal any adenoma or nodule. On one of follow-up labs, patient was noted to have hypomagnesemia (1.4mg/dL).

Additionally, at 4 years of age, patient started to have vision problem. This prompted an ophthalmology evaluation that showed macular scarring. At this time, a suspicion of FHHNC was raised and genetic testing subsequently confirmed a C59G mutation in CLDN 19.

Patient has been on thiazide and also on magnesium supplement since diagnosis.

Literature review: The product of CLDN19 belongs to the claudin family. It plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity. Defects in CLDN19 are the cause of hypomagnesemia renal with ocular involvement. This is a progressive renal disease characterized by primary renal magnesium wasting with hypomagnesemia, hypercalciuria and nephrocalcinosis associated with severe ocular abnormalities such as bilateral chorioretinal scars, macular colobomata, significant myopia and nystagmus.

There is no known cure, and treatment is largely supportive with thiazide diuretics and magnesium supplementation, although whether this helps to slow the rate of progression to end-stage renal disease is not clear at present.

Conclusion: FHHNC is a rare disorder of magnesium metabolism and often underdiagnosed. In particular, magnesium levels are often not checked and there is a spectrum of FHHNC in which the magnesium could be normal. FHHNC is a progressive disease in both renal and eyes however, the clinical course is not completely clear. Multidisciplinary approach is helpful in monitoring and management of this disease.