SAT-757 - Renal Tubular Acidosis, A Possible Cause for Severe Hypercalcemia of Infancy

Background:
Severe hypercalcemia in infancy is rare and presents a broad differential diagnosis, including endocrine, genetic, oncologic, infectious, and renal etiologies. We describe a 15-month-old male with persistent PTH-independent hypercalcemia and no clear unifying diagnosis despite extensive evaluation, raising the possibility of an atypical renal tubular acidosis (RTA)–associated presentation.

Case Presentation:
A previously healthy 15-month-old male, born to a mother without diabetes and with no prenatal or delivery complications, presented with diarrhea, dehydration, and severe persistent hypercalcemia (13.0 mg/dL). History was notable for poor weight gain and growth deceleration. Albumin, phosphorus, magnesium, and other electrolytes were normal, with ongoing mild metabolic acidosis. Renal function suggested a mild, transient acute kidney injury (AKI) attributed to dehydration. Parathyroid hormone (PTH) was appropriately suppressed; 25-hydroxyvitamin D was normal and 1,25-dihydroxyvitamin D was low, as expected. PTH-related peptide (PTHrP) was detectable (5.2 then 3.5 pmol/L) but within the normal range. Urinary studies showed appropriate calcium and phosphate handling (Ca/Cr clearance 0.016 mg/d;; tubular reabsorption of phosphate 0.92%). FGF23 was mildly elevated, likely reflecting a compensatory response to the hypercalcemia. Skeletal survey and bone turnover markers were unremarkable; however, nephrocalcinosis was present, suggesting chronic calcium hyperfiltration.
Management and Outcome:
Hypercalcemia around 13.0 mg/dL persisted despite intravenous hydration, calcitonin, and furosemide. A single small dose of intravenous pamidronate (0.125 mg/kg) was administered, resulting in gradual normalization of calcium levels over two months without hypocalcemia or need for additional doses. Ongoing management included close biochemical monitoring and further evaluation of calcium-sensing receptor pathways.
An extensive infectious, genetic, and oncologic workup—including tumor markers, imaging, echocardiography to complete evaluation for Williams syndrome, collagen type I C-telopeptide, vitamin A, vitamin B6 and B12, chromosomal microarray, and whole exome sequencing— all was unrevealing. Due to the recurrent mild metabolic acidosis, the patient was referred to nephrology. Genetic testing identified a maternally inherited SLC4A1 mutation consistent with RTA, a condition typically associated with hypercalciuria rather than hypercalcemia.

Conclusion:
This case underscores the diagnostic complexity of pediatric PTH-independent hypercalcemia and suggests that SLC4A1-associated RTA, particularly in the setting of intercurrent illness and acute kidney injury, may contribute to severe hypercalcemia, warranting further investigation.

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