Trial Information

Evaluation of Calcium Absorption in Patients With Rothmund-Thomson Syndrome

This is a laboratory experiment to evaluate bone calcium deposition in patients with
Rothmund-Thomson Syndrome (RTS).

This study includes one study visit during which subjects will be admitted to the inpatient
unit in the Pediatric GCRC at TCH where they will undergo comprehensive clinical evaluations
by a team of physicians familiar with RTS as well as bone-specific studies divided into four
parts. Procedures for this study may be combined with procedures for H-9106, another
protocol for patients with RTS by Dr. Wang.

Subjects will arrive at the GCRC at TCH after an overnight fast. Per TCH pain management
protocols, numbing creams and sprays will be offered to the subject prior to the blood draw.
Tylenol per TCH pain protocol is allowed. All food and beverages consumed at the GCRC will
be pre-arranged by the study dietitian and weighed by the GCRC nutrition staff. Additional
food is not allowed unless approved by the study dietitian.

Subjects will be asked to provide a 3-day written dietary history as well as food
preferences for the GCRC study day. For the first meal of the study day, subjects will
consume 180 mL of low-fat milk or orange juice to which 20 micrograms of 46Ca will have been
added. (If milk is used as the vehicle for the isotope, the 46Ca will be added 18-24 hours
in advance.)

Immediately after breakfast, subjects will receive 5 mg of 42Ca intravenously over 2-3
minutes. The beginning of this infusion will serve as Time 0. After the infusion is
complete, the catheter hub will be changed in preparation for the subsequent blood draws.
Samples for calcium isotope ratio measurement (0.5 ml of whole blood) will be obtained at 6,
12, 20, 40, 120, 180, 240, and 480 minutes after the infusion.

GCRC will provide weighed diets for the study day as directed by the study dietitian. Each
meal should contain approximately 300 mg of calcium and each snack should provide negligible
calcium. A complete 24-hour urine collection in 8 hour aliquots will be performed while at
the GCRC starting with the first void after the isotopes are given.

After completion of this 24 hour period, the subjects will be discharged. They will continue
to collect all of their urine in 8 hour aliquots for an additional 24 hours and then will
collect three spot urine samples each day for the next 6 days. These samples will then be
mailed to the CNRC research laboratory of Dr. Steven Abrams where they will be analyzed for
isotope ratios by mass spectrometry analysis.

Upon discharge, subjects will receive a food scale and instruction sheets on recording their
dietary intake for the next 3 days (i.e., weighed food record). While inpatient, the study
dietitian will instruct the family on the guidelines for recording this intake. After the 3
days, the food scale and records will be returned to the CNRC for analysis.