Abstract: SA-PO998

A Rare Case of De Novo Claudin 19 Mutation

Session Information

Category: Nephrology Education

  • 1302 Fellows and Residents Case Reports

Authors

  • Tan, Nhi, Kaiser Oakland Medical Center, OAKLAND, California, United States
  • Akber, Aalia, Kaiser Oakland Medical Center, OAKLAND, California, United States
  • Zheng, Sijie, Kaiser Oakland Medical Center, OAKLAND, California, United States
Background

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an autosomal recessive disorder caused by mutations in the tight junction proteins claudins. Claudins play a key role in regulating paracellular transport of ions in the thick ascending loop of Henle. Mutations lead to decreased cell membrane permeability, limiting reabsorption of magnesium and calcium. FHHNC may present as nephrocalcinosis, vision defects, and renal failure in childhood.

First described in 1972, more than 120 cases have been reported, though exact prevalence is unknown. Most cases are found within family clusters. We present a rare case of de novo claudin-19 mutation.

Methods

A 17-year-old Hispanic woman presented with 15 lb weight loss over 6 months, polyuria, and polydipsia. She had alwasy been a “picky eater” and shorter and thinner than her siblings. Past medical history noted macular dystrophy at age 3, and short stature less than fifth percentile and less than mid-parental height. Family history was unremarkable.

Labs were notable for end stage renal disease with a creatinine of 7.3 mg/dl, secondary hyperparathyroidism, hyperphosphatemia of 6 mg/dl, hypocalcemia of 7.4 mg/dl, normocytic anemia of 8.9 g/dl, but surprisingly hypomagnesemia of 1.2 mg/dl and mild metabolic acidosis for the degree of renal failure. Ultrasound showed atrophic kidneys with nephrolithiasis. Peritoneal dialysis was initiated.

Genetic testing revealed homozygous variant in CLDN 19 gene, NM_148960.2:c.59G>A(p.Gly20Asp). The variant p.Gly20Asp has been reported in heterozygous and homozygous individuals with FHHNC with ocular involvement and is the founder pathogenic variant in the Spanish and French population.

Conclusion

Treatment options are limited. Oral magnesium may be used to supplement tubular magnesium wasting. Amiloride can exert magnesium sparing effects. Thiazides increase calcium reabsorption in the distal tubule. None have significant effect and patients eventually progress to end stage renal disease. The only curative treatment is transplant, where calcium and magnesium excretion is normalized following transplant and there is no recurrence of the disease. In young patients who present with early ocular deficits, FHHNC should be evaluated. Given the limits of supportive care, and no recurrence of FHHNC with renal replacement, early transplant should be considered.