1195

Abstract

Introduction: ES is a 7 month old Amish male born full term with a history of failure to thrive,hypotonia and developmental delay. He was evaluated by the pediatrician one day prior to admission for increased hypotonia, decreased suck, and decreased cry along with constipation. He had labs drawn and was found to have elevated calcium to 19.4 mg/dL. Mom reported uncomplicated pregnancy; he had been exclusively breastfed but was started on formula to increase his weight gain in the week prior to admission. Mom reported she was taking no medications other than multivitamins daily, namely suppratherapeutic dosing for Vitamin E, C and B. At admission, his vital statistics were normal for age, he weighted 5.9 kg. He was awake and alert with generalized hypotonia, there was no clonus appreciated and the remainder of the physical exam as within normal limits. Repeat laboratory studies were done which showed normal complete blood count, elevated calcium of 16.3 mg/dL, ionized calcium of 3.4 mg/dL, phosphate of 3.4 mg/dL, low parathyroid hormone 9.8 pg/mL, low alkaline phosphatase 79 U/L, elevated 25-Hydroxy D total 60 ng/mL, 25-Hydroxy D2 <4.0 ng/mL, 25-Hydroxy D3 60 ng/mL, elevated uric acid 7.4 mg/dL, normal thyroid panel. Urine studies revealed elevated fractional excretion of calcium of 3 along with random calcium/creatinine ratio elevated to 1.6. An electrocardiogram revealed sinus rhythm with prolonged PR interval of 183 milliseconds along with notched T-waves. ES was placed on three times maintenance intravenous fluids of 5% dextrose normal saline with 20 mEq/L of potassium chloride along with furosemide 1 mg/kg/dose IV every six hours. His x-rays revealed mild generalized osteopenia and his renal ultrasound demonstrated bilateral medullary nephrocalcinosis. Aggressive intravenous hydration plus furosemide was continued for three days and his calcium normalized. His urine phosphoethanolamine and plasma B6 were normal, inconsistent with hypophosphatasia. His comparative genomic hybridization revealed a large area of homozygosity encompassing the CYP24A1 gene which encodes 24-hydroxylase. Further sequencing showed homozygosity for a 3 base pair deletion in exon 2 consisted with the diagnosis of idiopathic infantile hypercalcemia. He was discharged from the hospital after normalization of calcium and improvement in tone. Upon follow up, the mother admitted to giving ES 1250 IU/day of vitamin D for one week at 5 and 6 months of age, as well as cod liver oil gel caps, 135 IU/cap of vitamin D, daily for 5 days at 7 months of age Idiopathic Infantile Hypercalcemia is a rare diagnosis due to mutation in the CYP24A1 which encodes the enzyme responsible for the inactivation of 1,25-dihydroxyvitamin D3, leading to profound hypercalcemia, suppressed intact parathyroid hormone and hypercalciuria. The importance of vitamin D supplementation for the prevention of rickets in childhood is well known. The usual recommended daily index of vitamin D is 400 IU, however in the general population there is a wide margin of safety of toxic levels of vitamin D. There have been several studies evaluating similar cohorts of patients presenting with clinical symptoms of vitamin D intoxication several weeks after receiving intermittent high doses of vitamin D prophylaxis. Severe hypercalcemia can lead to extreme morbidity and mortality if not recognized and corrected expediently. The initial management for hypercalcemia is based on the severity of elevation and symptoms. Regimens usually employed include a combined approach with bisphosphonates, calcitonin, glucocorticoids, and calcimemetics along with hydration. In this case the most effective treatment for his underlying condition included the judicious use of aggressive hydration along with loop diuretics to promote calcium excretion which allowed for rapid normalization of calcium and improvement in neurologic and cardiac symptoms.