Aspartylglucosaminuria

Malm et al. (2004) conducted a five year follow-up after two siblings with AGU underwent HSCT using unrelated human leukocyte antigen-A, -B, and DR identical donors at age 10 years 5 months and 5 years 10 months, respectively. After 5 years no neuropsychologic or clinical deterioration was noted in either sibling. Additionally, both siblings had stable expression of AGA. Therefore, HSCT may arrest disease progression and could contribute to a better quality of life in individuals with AGU.

Arvio et al. (2001) described 19 young patients with AGU. Of the 19 individuals, 5 had undergone successful bone marrow transplantation between 1991 and 1997. Two patients who received transplants were more severely mentally retarded 7 and 5 years’ follow-up than the nontransplanted patients. Additionally, all 5 individuals experienced posttransplant complications. Therfore, Arvio et al. (2001) concluded that bone marrow transplantation should not be recommended to patients with AGU after infancy.

AGU is a rare condition and therefore HSCT use is based on limited safety and efficacy data in humans. The largest experience with HSCT for lysosomal storage diseases exists in Hurler syndrome, for which good long-term neurodevelopmental outcomes have been demonstrated. Therefore, it is possible that early HSCT during infancy may be beneficial in alleviating the disease symptoms and progression of AGU, including neurologic function[6].

Overall, the goal of HSCT is to cure the patient from the primary disease and restore complete physical and mental health condition; however, infertility is common after myeloablative HSCT conditioned with total body irradiation (TBI) and high doses of gonadotoxic drugs[7].

Female Fertility

HSCT conditioning often involves TBI and/or gonadotoxic drugs, both of which are associated with a high risk of ovarian failure in females[7,8]. The majority of female patients who are treated with TBI experience gonadal failure. In fact, 10% experience recovery of gonadal function and only 1.3% acheive pregnancy[7].

Vatanen et al. (2013) evaluated long-term ovarian function after allogenic HSCT in childhood and adolescence in 70 prepubertal female tranplant survivors and 22 adult transplant survivors (transplant occuring between 1987-2000; mean age of 9 years; age range 1-19 years). Results showed that 40/70 prepubertal females experienced spontaneous puberty, based onbreast development, and 30/70 experience spontaneous menarche. They found that there was a high risk of ovarian failure with conditioning TBI or Bu-based regimes prior to HSCT and intensive anti-leukemia therapy prior to HSCT, including CRT, decreased the possibility of spontaneous menarche.

Male Fertility

TBI and gonadotoxic drugs are typically used to condition patients prior to HSCT, both of which lead to absence of spermatozoa. In fact, TBI is the main cause of azoospermia in patients treated with HSCT. This is due to the fact that spermatogenic stem cells are more sensitive to chemotherapy and radiation than later stage germ cells, preventing the generation of newsperm cells[7].

Rovo et al. (2013) conducted a European Group for Blood and Marrow Transplantation (EBMT) large retrospective analysis of men who underwent HSCT and found that 81% of males receiving TBI presented withazoospermia and only 1% had normal sperm counts in follow-up spermanalysis.

Anserini et al. (2002) found that azoospermia is less frequent in patients conditioned with busulphan and cyclophosphamide (50%) and uncommon in those treated with cyclophosphamide alone. Suggesting, perhaps, that busulphan and cyclophosphamiade or cyclophosphamide alone may affect fertility less than traditional HSCT conditioning with TBI and gonadotoxic drugs.

“Long-term survivors are at risk of late complications interfering with health condition and quality of life after HSCT. Infertility is one among other complications that may occur after transplantation. Today it becomes more evident that patients treated with HSCT are at high risk of permanent infertility. Despite not being a life-threatening complication, infertility is associated with significant psychological distress for the recipient of HSCT and his family. Long-term survivors have a legitimate right of becoming parents of children. Today, there are reasonable options to preserve fertility in patients treated with HSCT. For most late effects that may appear after HSCT, surveillance and preemptive interventions are undertaken during long-term follow-up after transplantation. In contrast, fertility preservation needs to be decided and implemented before starting HSCT. Despite high patient’s interest in issues of fertility, a number of barriers impede clinicians to discuss overtly the risk of infertility and the option for fertility preservation with many patients undergoing HSCT. In addition, providing information and guidance about fertilitypreservation raises a number of ethical and legal considerations.”