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

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.

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.

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.