ESPE Abstracts (2015) 84 P-3-648

A Novel Mutation in CYP24A1 Gene in an Infant with Severe Hypercalcaemia and Unique Neurological Presentation

Yael Levy-Shragaa,b, Orit Pinhas-Hamiela,b, Dganit Dinourb,c & Dalit Modan-Mosesa,b


aPediatric Endocrine and Diabetes Unit, Sheba Medical Center, Edmond and Lily Safra Children’s Hospital, Ramat Gan, Israel; bSackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel; cDepartment of Nephrology and Hypertension, Sheba Medical Center, Ramat Gan, Israel


Background: Loss of function mutations of CYP24A1, encoding vitamin D-24-hydroxylase, have been recently identified in idiopathic infantile hypercalcemia (IIH), a rare entity which may lead to severe complications.

Objective: We describe a unique neurological presentation in an infant with IHH due to a novel CYP24A1 mutation.

Case presentation: The patient was born at term after normal pregnancy to healthy non-consanguineous parents. He presented at age 7 months with weakness, failure to gain weight, and developmental arrest in the preceding 2 months. Physical examination revealed pale, thin, apathetic infant with severe hypotonia and tonic upward gaze. Laboratory investigation revealed severe hypercalcemia of 20.3 mg/dl (normal 7.2–10), ionized calcium 2.7 mmol/l (normal 1.0–1.2), phosphate 3.8 mg/dl (normal 4.7–8.0), PTH<3 pg/ml (normal 16–87), 25-hydroxy-vitamin D 53 ng/ml (normal 30–100), and 1.25dihydroxy-vitamin D 92 pg/ml (normal 20–100). Urine calcium excretion was elevated, with calcium/creatinine ratio of 2.3 (normal for age <0.8). Renal ultrasonography demonstrated normal-sized kidneys without nephrocalcinosis. After acute management with fluids, diuretics, pamidronate and calcitonin, calcium level decreased to 9.6 mg/dl, and the patient was discharged on low-calcium formula with no supplemental vitamin D. A month later, calcium level increased to 12.9 mg/dl and he received a second dose of pamidronate. Currently, the patient is 13 months old, with normal calcium level with no additional treatment; however, the neurological symptoms did not completely resolve. DNA was extracted from whole blood and full sequencing of the coding regions of the CYP24A1 gene was performed and revealed that the patient is a compound heterozygote of two mutations: E143del in exon 2 (a mutation that has been previously reported) and a novel truncating mutation in exon 8 (c.995_1001delCAAACAG). Each parent carried one of the mutations. The result of whole exome sequencing is pending.

Conclusion: This patient presents a case of severe hypercalcaemia and to a novel CYP24A1 mutation associated with neurologic deterioration and tonic upward gaze that have not been previously reported in IHH.

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