Background: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare, autosomal recessive condition caused by mutations in CLDN16 or CLDN19, which encode for tight junction proteins, claudin-16 and claudin-19, respectively. This condition often has a delayed diagnosis in patients with no prior family history due to a lack of specific clinical symptoms. Description of case, diagnosis, and treatment: A 4-year, 10-month-old Caucasian boy presented with failure to thrive, developmental delay, and ocular findings consisting of horizontal nystagmus, bilateral macular staphylomas, and high myopia. Laboratory studies revealed hypercalciuria, hypomagnesemia, and renal insufficiency. Renal ultrasound showed bilateral small kidneys with medullary nephrocalcinosis. Candidate gene sequencing performed at age 7 years identified a novel, homozygous, frameshift mutation c.140_141delAT (p.Tyr47Stop) within CLDN19, confirming the molecular diagnosis of FHHNC. Due to rapid renal progression, the proband underwent renal transplant at age 10 years, 10 months. FHHNC was prenatally diagnosed in the proband's sister, who was found at birth to have ocular findings and hypomagnesemia. In addition, she had feeding intolerance and persistent hypoglycemia with hyperinsulinism that has required chronic diazoxide therapy.
Conclusions: Although rare, FHHNC should be suspected in patients who present with nephrocalcinosis in the setting of congenital eye anomalies..