Clinical and genetic analysis of tuberous sclerosis complex-associated renal angiomyolipoma in Chinese pedigrees

Tuberous sclerosis complex-associated renal angiomyolipoma (TSC-RAML) confers a high risk of bleeding and even mortality. However, data on TSC-RAML in Chinese pedigrees is extremely lacking. The present study aimed to investigate its clinical and genetic characteristics by obtaining a detailed medical history from 6 probands and their family members, and reassessing blood tests, computed tomography and renal dynamic imaging examinations that were conducted in the TSC-RAML patients. The TSC1/TSC2 mutation was detected in 2 families. A total of 3 TSC-RAML patients underwent partial nephrectomy due to a high bleeding risk, and the other 2 were treated with everolimus. The remaining 6 TSC-RAML patients received no clinical intervention and only had clinical follow-uzp. It was found that nearly 37% (18/49) were TSC patients, with the mean +/- standard deviation diagnostic age being 34.22 +/- 17.73 years old in the 6 pedigrees, 61% (11/18) of whom suffered from TSC-RAML. In the 11 TSC-RAML patients, the maximum diameter of the tumor ranged between 1.20 and 32.50 cm (mean +/- standard deviation, 11.48 +/- 8.40 cm), the unilateral glomerular filtration rate ranged between 27.20 and 60.10 ml/min (mean +/- standard deviation, 42.55 +/- 9.73 ml/min), the serum creatinine level ranged between 40.00 and 90.00 mu mol/l (mean +/- standard deviation, 64.84 +/- 16.15 mu mol/l) and the hemoglobin concentration ranged between 76.00 and 140.00 g/l (mean +/- standard deviation, 107.73 +/- 21.04 g/l). Pathogenic mutations of TSC1 (c.733C> T) and TSC2 (c.788_789insC) were detected in family B and C, respectively, as well as certain non-pathogenic mutations, with the maximum diameter of TSC-RAML being 0 cm and 10.3 cm in the two patients from family B and 16 cm and 1.2 cm in the two patients from family C. Expression of phosphorylated-mechanistic target of rapamycin was determined in the TSC-RAML tissues by immunohistochemistry. The maximum diameter of the tumor decreased by 4.90 and 5.30 cm, respectively, in the 2 patients treated with everolimus after 3 months. In conclusion, TSC cannot be easily diagnosed due to its variable characteristics. Growth of TSC-RAML may increase the bleeding risk and reduce the level of hemoglobin, but it does not greatly affect renal function. Individual differences in tumor dimensions existed even with the same pathogenic mutation, except for cases of coexistent non-pathogenic mutations. Everolimus treatment appears to be able to significantly reduce the size of TSC-RAML.