Nina Lenherr-Taube1, Michelle Furman1, Esther Assor1, Yesmino Elia1, Carol Collins2, Kenneth Thummel2, Michael A Levine3, Etienne Sochett1. 1. Department of Pediatrics, Division of Endocrinology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. 2. Department of Pharmaceutics, University of Washington, Seattle, WA, USA. 3. Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia and Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Abstract
CONTEXT: Idiopathic infantile hypercalcemia (IIH) is an uncommon disorder with variable clinical features. The natural history and response to dietary calcium and vitamin D restriction in IIH remains unclear. OBJECTIVE: The aim of this study is to describe the clinical and biochemical response to dietary calcium and vitamin D restriction in a genetically characterized cohort of mild IIH. METHODS: This is a longitudinal, observational cohort study of 20 children with mild IIH monitored for a median of 21months. Biochemical measures, dietary assessment, and yearly renal ultrasound results, since the time of diagnosis, were obtained and assessed prospectively every 4 to 6 months. RESULTS: Median age at initial diagnosis was 4.5 months. Median levels of serum calcium (2.82 mmol/L) and 1,25 (OH)2D (192 pmol/L) were elevated, whereas serum PTH was reduced (10 ng/L). Urinary calcium:creatinine ratio was elevated for some, but not all individuals (median 1.49 mmol/mmol). All patients who were managed with a low-calcium diet showed an improvement in serum and urinary calcium measures, but the serum concentration of 1,25 dihydroxyvitamin D (1,25(OH)2D) and 1,25(OH)2D/PTH ratio remained elevated. In 2 of the 11 subjects, renal calcification worsened. There were no differences in response between individuals with CYP24A1 or SLC34A1/A3 variants. CONCLUSION: The clinical presentation of mild IIH is variable, and dietary calcium and vitamin D restriction does not consistently normalize elevated 1,25(OH)2D concentrations or prevent worsening of renal calcification in all cases. Therapeutic options should target the defect in vitamin D metabolism.
CONTEXT: Idiopathic infantile hypercalcemia (IIH) is an uncommon disorder with variable clinical features. The natural history and response to dietary calcium and vitamin D restriction in IIH remains unclear. OBJECTIVE: The aim of this study is to describe the clinical and biochemical response to dietary calcium and vitamin D restriction in a genetically characterized cohort of mild IIH. METHODS: This is a longitudinal, observational cohort study of 20 children with mild IIH monitored for a median of 21months. Biochemical measures, dietary assessment, and yearly renal ultrasound results, since the time of diagnosis, were obtained and assessed prospectively every 4 to 6 months. RESULTS: Median age at initial diagnosis was 4.5 months. Median levels of serum calcium (2.82 mmol/L) and 1,25 (OH)2D (192 pmol/L) were elevated, whereas serum PTH was reduced (10 ng/L). Urinary calcium:creatinine ratio was elevated for some, but not all individuals (median 1.49 mmol/mmol). All patients who were managed with a low-calcium diet showed an improvement in serum and urinary calcium measures, but the serum concentration of 1,25 dihydroxyvitamin D (1,25(OH)2D) and 1,25(OH)2D/PTH ratio remained elevated. In 2 of the 11 subjects, renal calcification worsened. There were no differences in response between individuals with CYP24A1 or SLC34A1/A3 variants. CONCLUSION: The clinical presentation of mild IIH is variable, and dietary calcium and vitamin D restriction does not consistently normalize elevated 1,25(OH)2D concentrations or prevent worsening of renal calcification in all cases. Therapeutic options should target the defect in vitamin D metabolism.
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Authors: Nina Lenherr-Taube; Edwin J Young; Michelle Furman; Yesmino Elia; Esther Assor; David Chitayat; Tami Uster; Susan Kirwin; Katherine Robbins; Kathleen M B Vinette; Alan Daneman; Christian R Marshall; Carol Collins; Kenneth Thummel; Etienne Sochett; Michael A Levine Journal: J Clin Endocrinol Metab Date: 2021-09-27 Impact factor: 6.134