Endocrine Abstracts

JOINT3564

Background: The ABCD syndrome (ABnormal Calcium, Calcinosis, and Creatinine in Down syndrome) is a rare cause of persistent hypercalcemia in children with trisomy 21, which typically occurs in the first 2 years of life. To date, 12 patients have been reported. Here we present a new case and review the literature of this under-reported clinical entity. Case: A 21-month-old toddler with trisomy 21 presented with a 6-month history of recurrent vomiting, failure to thrive, and bilateral nephrocalcinosis grade IIb of unknown origin. Laboratory results revealed hypercalcaemia (3. 37 mmol/l), hypermagnaesemia (1. 16 mmol/l), normophosphataemia and impaired renal function (creatinine 0. 80 mg/dl, (normal range 0. 19-0. 39 mg/dl)). Further tests showed undetectable serum PTH, low 1, 25(OH)2D, elevated urinary calcium/creatinine ratio (3. 6 mmol/mmol). Vitamin A and 25-hydroxyvitamin D (74. 3 ng/mL) were both outside toxic ranges. The patient had received only routine vitamin D supplementation, with no other medication or supplements and no special diet, without excess of milk products. Adrenal insufficiency and malignancy were excluded. Trio whole exome sequencing identified no pathogenic variants linked to hypercalcemia. Since intravenous fluids failed to normalize calcium levels, a single dose of pamidronate (1mg/kg) was administered and low-calcium diet commenced. Serum calcium levels and renal function subsequently normalized before discharge. Follow-up examinations at two and four weeks confirmed sustained normal values for calcium, phosphate, PTH and calcium excretion, under continued dietary calcium restriction.

Discussion/Conclusion: Most reported cases of ABCD syndrome had similar biochemical profiles of calcium overload of PTH-independent cause, such as hypercalcaemia, hypercalciuria, nephrocalcinosis and acute kidney injury. The rapid improvement of hypercalcaemia following calcium intake reduction suggests increased intestinal calcium absorption as a potential mechanism. The diagnostic approach requires exclusion of other causes of hypercalcemia. Our case and literature review highlight the importance of raising awareness about ABCD syndrome to ensure timely diagnosis and intervention. Early recognition can help reduce the risk of complications such as kidney injury and prolonged failure to thrive.