Calcium Overload in Trisomy 21: An Underrecognized Cause of Persistent Hypercalcaemia - A Case Report.

Abstract

Introduction: Calcium overload in trisomy 21 is a rare and underrecognized cause of persistent parathyroid hormone (PTH)-independent hypercalcaemia in infants and young children with Down syndrome. Characteristic features include hypercalciuria, nephrocalcinosis, renal impairment, and failure to thrive. Delayed recognition may result in avoidable long-term complications.

Case presentation: A 21-month-old boy with trisomy 21 presented with a six-month history of recurrent vomiting, feeding difficulties, and failure to thrive. Bilateral nephrocalcinosis was detected incidentally on abdominal ultrasound. Laboratory evaluation revealed marked hypercalcaemia with suppressed PTH and 1,25(OH)₂D, hypercalciuria, and acute kidney injury. Extensive diagnostic work-up excluded alternative causes of PTH-independent hypercalcaemia. Nutritional assessment showed an almost exclusively milk-based diet with minimal solid food intake. Initial treatment with intravenous fluids and a single dose of pamidronate resulted in only transient improvement. Following the diagnosis of calcium overload, a calcium-restricted diet consisting of normal and low-calcium formula was introduced and adjusted according to biochemical response. Serum calcium normalized and remained stable throughout 11 months of follow-up. Growth and developmental progress improved, while nephrocalcinosis persisted and renal function partially recovered.

Conclusion: Calcium overload in trisomy 21 should be considered in young children with Down syndrome presenting with failure to thrive, recurrent vomiting, and nephrocalcinosis in combination with PTH-independent hypercalcemia. Early recognition and initiation of dietary calcium restriction may prevent long-term complications such as chronic kidney disease and prolonged growth impairment.