AN UNCOMMON CAUSE OF PERSISTENT HYPERCALCAEMIA WITH NEPHROCALCINOSIS IN INFANCY

Abstract

INTRODUCTION
Hypercalcaemia with nephrocalcinosis in infants is commonly caused by excessive calcium or vitamin D supplementation, neonatal primary hyperparathyroidism, subcutaneous fat necrosis or various genetic disorders.

CASE
We present a 6-month-old Indian male infant who was born preterm at 33 weeks, via elective LSCS for polyhydramnios with weight of 1.33 kg, length of 46 cm and head circumference of 27 cm. His mother had severe polyhydramnios, requiring amnioreduction thrice. Both parents were consanguineous. During his 3-month-stay at NICU, he had persistent hypercalcaemia with intermittent polyuria. Serum calcium ranged: 2.5–2.9 mmol/L, phosphate: 1.85–3.05 mmol/L, alkaline phosphatase (ALP): 500–800 IU/L and 25(OH)D₃: 200 nmol/L. He also had hypochloraemic hypokalemic metabolic alkalosis, hyperreninemia (>550 mU/L) and hyperaldosteronemia (>3656 pmol/L). Ultrasound at 2-month-old demonstrated bilateral renal medullary nephrocalcinosis and cholelithiasis. Skeletal survey revealed no significant bony abnormalities. There were episodes of hyponatremia and hypokalemia, which improved spontaneously. Clinically, he had prominent forehead, triangular face, right hand pre-axial polydactyly and bilateral short distal phalanx of the 4th and 5th fingers with nail hypoplasia. His weight gain was poor with delayed motor development and hypotonia. At 6-month-old, his care was shared by paediatric nephrologist and endocrinologist. He was 3.57 kg with a length of 57.8 cm. His iPTH later resulted in relatively inappropriately raised level, (Ca: 2.81 mmol/L, PO₄: 1.87 mmol/L, ALP: 770 IU/L, iPTH: 68.3 pg/mL). Urinalysis showed profound natriuresis and hypercalciuria (24-hour urine Ca: 5.3 mg/kg/day). Ultrasound of the thyroid exhibited no abnormality. The parents’ calcium profiles were normal. Pamidronic acid (1 mg/kg/dose) was given (when serum calcium >3.0 mmol/L) but the hypercalcemia only transiently improved. Eventually, he was treated with indomethacin and free water supplement. The whole exome sequencing revealed a heterozygous pathogenic variant in ROR2 gene and a homozygous variant of uncertain significance in KCNJ1 gene.

CONCLUSION
Antenatal Bartter syndrome presents insidiously during neonatal period, typically with polyhydramnios, IUGR, prematurity, polyuria and failure to thrive. It can present with nephrocalcinosis accompanied by features resembling primary hyperparathyroidism. Genetic testing enhances the diagnostic precision of various Bartter syndrome subtypes.