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Abstract: SA-PO569

Novel KCNJ1 Mutations Responsible for Adult Bartter Syndrome With Hypocalcemia

Session Information

  • Genetic Diseases: Diagnosis
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

  • 1102 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Chen, Chien-Chou, Tri-Service General Hospital, Taipei, Taiwan, Taiwan
  • Sung, Chih-Chien, Tri-Service General Hospital, Taipei, Taiwan, Taiwan
  • Tseng, Min-hua, Chang Gung Memorial Hospital, Taoyuan, Taiwan, Taiwan
  • Lin, Shih-Hua P., Tri-Service General Hospital, Taipei, Taiwan, Taiwan

Group or Team Name

  • Division of Nephrology, Tri-Service General Hospital
Introduction

Bartter syndrome (BS) is a rare, autosomal recessive disease, caused by gene mutations of the transporters or channels of thick ascending loop of Henle (LOH) responsible for sodium chloride (NaCl), potassium (K+) and calcium (Ca++) reabsorption. Accordingily, it is characterized by persistent renal salt wasting with secondary hyperreninemia and hyperaldosteronism, renal K+ wasting with hypokalemic metabolic alkalosis with renal K+ wasting, and hypercalciuria with nephrocalcinosis and/or nephrolithiasis. The clinical manifestations of genetic BS vary dramatically from asymptomatic, polyuria, polydipsia, premature delivery, polyhydramnios and failure to thrive, but ususally presenting at antenatal and neonatal period other than adulthood.

Case Description

A 28-year-old Chinese female was referred for the evaluation for chronic hypocalcemia, medullary nephrocalcinosis, and hypokalemia. Two years ago, she first presented with severe symmetrical general muscle weakness, muscle tetancy, spasm, and polyuria and was found to have moderate hypokalemia with metabolic alkalosis and renal potassium (K+) wasting, hypocalcemia (7.0 mg/dl) with an increased serum parathyroid hormone, hypercalciuria and bilateral medullary nephrocalcinosis. A thorough search for the identifiable causes such as autoimmune disorders, inflammation, malignancy, and use of diuretics was non-revealing. Genetic sequencing of calcium sensing receptor (CaSR) was negative. Using next generation sequencing based mutation screening with Sanger sequencing in her family, compound heterozygous mutations c.346_357del (p.116_119del) and c.1074 C>A (p.C358X) in KCNJ1 inherited from her parents was identified. These two KCNJ1 mutations were novel and pathogenic variants. Treatment with cyclooxygenase-2 (COX2) inhibitor, K+ and calcium supplementation achieved a remarkable improvement in her clinical feature and laborabory abnormality.

Discussion

Although hypercalciuria in the prescene of peristed renal salt wasting, metabolic alkalosis and medullary nephrocalcinosis are the landmark findings for BS, serum calcium, phosphate and PTH may help differentiate between type I/II and V. Genetic form of late or adult BS, albeit rare, should be kept in mind as a cause of chronic hypokalemia with salt wasting and nephrocalcinosis/ nephrolithiasis, even in the presence of hypocalcemia.