Long-term administration of sirolimus does not affect the physical development of children with tuberous sclerosis...

There was no evidence whether the mammalian/mechanistic target of rapamycin pathway hyperactivation and long-term use of mTOR inhibitors have any effects on the physical development of children. The aim was to evaluate these effects by comparing the physical development of children with TSC and normal children.

A total of 120 eligible children were enrolled. They were administered sirolimus and followed for at least 12 months. Height, weight, BMI and lipid metabolism index were collected during treatment. Pearson's chi-square and Fisher's exact test were used for comparison of proportions of patients exhibiting normal and abnormal physical growth before and after 1 year of treatment. Logistic regression was used to evaluate the influence of age, sex and abnormal lipid metabolism on the increased BMIs of TSC patients after treatment.

Most of the enrolled TSC children were in the normal height, weight and BMI ranges at baseline (91.7%, 95.8% and 78.3%, respectively). Most remained in the normal height, weight and BMI ranges after 1 year of sirolimus treatment (94.2%, 95% and 76.7%, respectively). There was no significant difference in the proportion of physical development before and after treatment (p > 0.05). Thirty-eight (38/106, 35.8%) patients had increased BMIs after 1 year of treatment, but there was no significant correlation between age, sex and lipid metabolism and increased BMI.

Overactivation of the mTOR pathway and long-term administration of sirolimus does not affect the physical development of children with TSC.