Background: Rett syndrome (RTT), an X-linked neurodevelopmental disorder primarilyaffecting girls, is characterized in part by osteopenia and increased risk of skeletal fractures. We hypothesized that decreased intestinal calcium (Ca) absorption relative to dietary Ca intake and increased renal Ca excretion might cause these problems in RTT.
Objective: We measured fractional Ca absorption, urinary Ca loss, dietary Ca intake, and the hormonal factors regulating Ca metabolism to determine whether abnormalities in Ca balance might relate to poor bone mineralization in RTT girls and to evaluate the contribution of these factors to the overall dietary Ca needs of RTT girls.
Study design: Ten RTT girls and 10 controls, matched for age, sex, and pubertal status, were given a 3 day constant Ca diet that mimicked their habitual intakes. At the end of each dietary period, girls received single doses of Ca (intravenous) and Ca (oral). Fractional urinary excretion of Ca, Ca, 24 hour urinary Ca, and urinary cortisol excretion were determined. Serum Ca, phosphorous, alkaline phosphatase, vitamin D metabolites, parathyroid hormone (PTH), and osteocalcin were measured in the postabsorptive state. Bone mineral content (BMC) was measured by dual-energy x-ray absorptiometry.
Results: Fractional Ca absorption was significantly higher in RTT than in control girls (mean +/- SDp, 52 vs. 33 +/- 13%). Dietary Ca intake (mean +/- SDp, 1,100 vs. 1,446 +/- 440 g/d) and net Ca absorption (mean +/- SDp, 513 vs. 362 +/- 306 mg/d) did not differ significantly between RTT and controls, respectively. Although urinary Ca excretion did not differ between groups, the increased urinary Ca:creatinine ratio (mean +/- SDp, 0.39 vs. 0.23 +/- 0.38) was consistent with clinical hypercalcuria and paralleled the significantly increased urinary cortisol excretion (mean +/- SDp, 3.1 vs. 1.7 +/- 1.1 mg/kg lean body mass per day) in the RTT girls. BMC was significantly lower in RTT than in controls (mean +/- SDp, 527 vs. 860 +/- 275 g). Serum Ca, P, alkaline phosphatase, vitamin D metabolites, PTH, and osteocalcin concentrations did not differ between the groups.
Conclusion: Fractional Ca absorption showed a compensatory increase in the presence of adequate dietary Ca intakes, mild hypercalcuria, and pronounced bone mineral deficits in RTT girls. Whether supplemental dietary Ca could enhance fractional Ca absorption and improve bone mineralization in RTT girls is unknown.