Introduction

Autosomal dominant hypocalcemia type 1 (ADH1) is a rare genetic endocrine disorder caused by an inherited or de novo heterozygote activating mutation of the calcium-sensing receptor (CaSR) gene, located on chromosome 3q13.3–q21. In ADH1, the CaSR is activated, even in the presence of normal or low serum calcium levels, resulting in the suppression of PTH synthesis and release, a decrease in renal Ca+2 reabsorption, causing hypocalcemia with relative hypercalciuria. ADH1 prevalence was estimated at 3.9 per 100,000 in a recent study of 51,289 subjects from a single US healthcare system. Over 100 distinct germlineactivating mutations of the CaSR gene have been described in association with ADH1. The mode of inheritance is usually autosomal dominant; however, sporadic mutations have also been reported and the diagnosis can be confirmed by DNA analysis. The patient in question in this case is one of the sporadic mutation variants. The clinical presentation of ADH1 is heterogeneous and may vary from mild hypocalcemia which is not diagnosed until late adulthood, to more severe presentations during infancy or childhood with recurrent seizures. This case is to present adjustments in medication management in maintaining close to normal calcium levels in an adolescent male whose activity level varied with high school sports during the two-year period followed.

Case Presentation

The patient has a disorder of an activating mutation of the calcium-sensing receptor (CaSR) gene which was initially presented at 3 weeks of age due to observed seizures resulting from severe hypocalcemia. Occasional admissions in an inpatient setting were needed to address and correct periods of both hypocalcemia and hypercalcemia. He has been treated with various doses of calcitriol, calcium carbonate, and hydrochlorothiazide. The calcitriol was a concentrated solution of 1mg/ml regimen. Calcium carbonate was given in the form of OTC TUMS. Hydrochlorothiazide was initially given in oral concentration of 50mg/cc and then to oral doses of 12.5mg tablets. The patient was followed over a 2-year period during his adolescence of ages 15 through 16 while attending a large, public high school in the Northern California area. During these years, the patient (MK) was noted to have a 2-inch growth and was involved in year-round sports with varying degrees of activity intensity [1-3]. Patient MK was also noted to have periods of inactivity when recovering from surgeries involving removal of pectus bar for repair of pectus xcavatum and from a broken right thumb needing casting (which ended his seen prematurely). His calcium level was monitored weekly with adjustments in his medication regimen made to correct his calcium level with the goal of being in normal range. This was pursued to allow the patient to continue to participate in his high school athletic activities. What was observed was the expected utilization of calcium during periods of growth and increased activity resulting in instances of potential hypocalcemia as well as elevated calcium levels seen when there was a decrease in activity and when recovering from surgery. Calcium levels were checked weekly, and his medication regimen was adjusted accordingly to maintain low normal values. Changes were made for the sole target of the calcium level to be close normal levels allowing the patient MK to continue to participate in sport [4,5].

Data

[Left Y-axis (calcium level and number of days per week of practice), X-axis (date), Right Y-axis (calcitriol dose)] (Figure 1-3).

Figure 1: Calcitriol Dose, Lab Result and Activity Level (2020-2022).

Figure 2: Calcitriol Dose, Lab Result and Activity Level (2022-2023).

Figure 3: Calcitriol Dose, Lab Result and Activity Level.