Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
J Clin Endocrinol Metab. 2021 Jan 23;106(2):e485-e495. doi: 10.1210/clinem/dgaa759.
The ketogenic diet is associated with progressive skeletal demineralization, hypercalciuria, and nephrolithiasis. Acute hypercalcemia has been described as a newly recognized complication of this treatment.
To describe the clinical characteristics of acute hypercalcemia in children on the ketogenic diet through analysis of the presentation, response to treatment, and natural history in a large cohort of patients.
A multicenter case series was performed including children who developed acute hypercalcemia while treated with the ketogenic diet. Information on clinical presentation, treatment, and course of this complication was collated centrally.
There were 14 patients (median (range) age 6.3 (0.9 to 18) years) who developed hypercalcemia 2.1 (range, 0.2-12) years after starting the ketogenic diet. All had low levels of parathyroid hormone and levels of 1,25-dihydroxyvitamin D were low in all except one. Seven (50%) had impaired renal function at presentation. All except the 2 oldest had low alkaline phosphatase levels for age. Once normocalcemia was achieved, hypercalcemia recurred in only 2 of these patients over observation of up to 9.8 years. One patient discontinued the ketogenic diet prior to achieving normocalcemia while 4 more stopped the diet during follow-up after resolution of hypercalcemia.
Ketotic hypercalcemia can occur years after starting the ketogenic diet, especially in the setting of renal impairment. The mechanism is unknown but appears to be due to reduced osteoblast activity and impaired bone formation. We recommend close attention to optimizing bone health in these children, and screening for the development of ketotic hypercalcemia.
生酮饮食与进行性骨骼脱矿质、高钙尿症和肾结石形成有关。急性高钙血症已被描述为这种治疗的新出现的并发症。
通过分析大量患者的临床表现、对治疗的反应和自然病史，描述生酮饮食儿童急性高钙血症的临床特征。
进行了一项多中心病例系列研究，包括在接受生酮饮食治疗时发生急性高钙血症的儿童。集中收集了关于临床表现、治疗和该并发症病程的信息。
有 14 名患者（中位数（范围）年龄 6.3（0.9 至 18）岁）在开始生酮饮食 2.1（范围，0.2-12）年后发生高钙血症。所有患者甲状旁腺激素水平均较低，除 1 例外，1,25-二羟维生素 D 水平均较低。7 名（50%）患者在发病时肾功能受损。除 2 名年龄最大的患者外，所有患者的碱性磷酸酶水平均低于年龄正常值。一旦达到正常钙血症，除 2 名患者在长达 9.8 年的观察中再次出现高钙血症外，其余患者均未再次出现高钙血症。在达到正常钙血症之前，有 1 名患者停止了生酮饮食，而另外 4 名患者在高钙血症缓解后停止了生酮饮食。
酮症性高钙血症可在开始生酮饮食多年后发生，尤其是在肾功能受损的情况下。其机制尚不清楚，但似乎与成骨细胞活性降低和骨形成受损有关。我们建议密切关注这些儿童的骨骼健康，并筛查酮症性高钙血症的发生。
