6518 A Family Affair: A Case of Idiopathic Infantile Hypercalcemia
Authors: Hu Tina Y , Gao Josephine , Ekhlaspour Laya , Wallerstein Robert , Erkin-Cakmak Ayca 
Published: October 2024

Disclosure: T.Y. Hu: None. J. Gao: None. L. Ekhlaspour: None. R. Wallerstein: None. A. Erkin-Cakmak: None.

Introduction: Idiopathic infantile hypercalcemia (IIH) is a rare cause of hypercalcemia in infants and can be due to a deficiency in 25-Hydroxyvitamin D 24-hydroxylase (CYP24A1), inherited autosomal recessively, resulting in impaired degradation of calcitriol and hypercalcemia. Symptomatic infants may have vomiting, poor feeding, and failure to thrive. Most are unaffected while others develop transient hypercalcemia and/or hypocalcemia. Case studies suggest initial monitoring with serum and urine calcium, phosphorous, vitamin D, and PTH, avoiding dietary calcium and vitamin D, and supplementing phosphorous. However, guidance is lacking for lab frequency and further management. Case: A full-term baby girl is born to a 37-year-old G1P1 mom with CYP24A1 mutation and borderline hypercalcemia since age 18. During pregnancy, mom developed symptomatic hypercalcemia after prenatal vitamins (and suspected placental source of 1,25-dihydroxyvitamin D) requiring admission. Maternal work-up revealed elevated 25(OH)D3:24,25-(OH)2D3 ratio and two variants in CYP24A1: pathogenic c.1186C&gt;T, p.Arg396Trp and VUS c.544-17G&gt;A (p?). At delivery, mom’s corrected calcium was 11.4 mg/dL. No prior testing for calcium abnormalities or CYP24A1 mutation for dad. On day of life (DOL) 0, patient had normal iCal (1.36 mmol/L, [1.13 - 1.35 mmol/L]) and phosphorous (4.7 mg/dl, [4.3-9.3 mg/dl]). Initial labs included PTH, iCal Q12 hours, and phosphorous. Breastfeeding trial led to hypercalcemia (DOL2 iCal 1.32 mmol/L to DOL3 iCal 1.69 mmol/L). iCal monitoring was increased to Q6 then Q3 hours on DOL3. Despite transition from breastfeeding to Similac low calcium infant formula, iCal increased to 1.77 mmol/L. Ultimately, transition to donor breast milk resulted in decrease in iCal to 1.65 mmol/L then 1.32 mmol/L within 9 hours. Labs remained normal at 2 months while on primarily maternal and donor breastmilk (serum calcium, iCal, albumin, magnesium, phosphorous, PTH, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D) and at 7 months after starting baby food. At 12 months, 25-hydroxyvitamin D rose from 28-44 ng/mL to 60 ng/mL due to sunlight exposure with reminder to limit exposure. Outpatient labs with calcium, albumin, magnesium, phosphorous, vitamin D, and PTH levels were spaced to every 3-5 months given stability. Invitae genetic testing revealed two pathogenic variants in CYP24A1 with CYP24A1 associated with autosomal recessive infantile hypercalcemia (C.1186C&gt;T (p.Arg396Trp)), but not the same two variants found in mom. Dad was subsequently found to be a carrier of one of the pathogenic CYP24A1 variants found in the patient (c.428_430del (p.Glu143del)). Conclusion: IIH is a rare disorder and can go unrecognized especially if parental status is unknown (carrier/CYP24A1 mutation). This case adds to literature with details on labs, frequency, and management beyond avoiding dietary calcium and vitamin D.

Presentation: 6/3/2024