ESPE Abstracts

Background: Primary hypogonadism in females is characterized by inadequate ovarian function, resulting in insufficient or absent production of estrogens. This case report aims to present a rare case of primary amenorrhea in a female child where bone marrow transplantation (BMT) was performed due to the beta-thalassemia.

Case presentation: A 14-year-old girl approached the endocrinology department for evaluation due to delayed puberty. Medical history showed that the child had major form of beta thalassemia. Before BMT, the patient was on a polytransfusion regimen and received chelation therapy due to iron overload till 9^th year of age when she underwent BMT from a male unrelated donor. Her twin brother who also had beta thalassemia and had BMT developed normal puberty. At the time of the examination, the girl is on 3^rd percentile curve for the height. She had normal female genitalia, however she lacked secondary sexual characteristics and was classified as Tanner stage 1 for puberty. Bone maturation was delayed - 12 years. Laboratory tests indicated very low estrogen levels and significantly elevated gonadotropins follicle-stimulating hormone [FSH] and luteinizing hormone [LH], in addition to primary hypergonadotropic hypogonadism. Ultrasonography and MRI showed that no ovaries were present, and the uterus was hypoplastic. Since she had karyotype of the donor - 46 XY, Barr bodies of the oral mucosa were performed showing 9%-which was normal result for a female. Molecular analysis from the DNA sample taken before the BMT-multiplex ligation probe amplification [MLPA] using kits R106-MRX, P036-subtelomeres mix 1, P070-Subtelomeres mix 2B, P185-Intersex and P334-Gonadal, showed no deletions or duplications of the examined × chromosome regions. There was no positive markers for Y chromosome in that sample as well. Marker for Y chromosome was found on the buccal smear and was considered as contamination from the blood. Тhe child was placed on estrogen therapy.

Discussion and Conclusion: Ovarian tissue is prone to severe impairment due to the many reasons. In this case we can speculate if the damage had been done due to the primary disease and repetitive transfusion which is unlikely since the child regularly received chelation therapy. The other factor could be whole body radiation prior to BMT, however her brother who underwent the same procedure developed normal puberty. The influence of a male donor to the ovarian dysfunction is not well described in the literature so far and should be further evaluated. Also we couldn’t entirely exclude somatic mosaicism prior the intervention.