Urogenital Abnormalities in Adenosine Deaminase Deficiency

Abstract

Background Improved survival in ADA-SCID patients is revealing new aspects of the systemic disorder. Although increasing numbers of reports describe the systemic manifestations of adenosine deaminase deficiency, currently there are no studies in the literature evaluating genital development and pubertal progress in these patients.Methods We collected retrospective data on urogenital system and pubertal development of 86 ADA-SCID patients followed in the period 2000-2017 at the Great Ormond Street Hospital (UK) and 5 centers in Italy. In particular, we recorded clinical history and visits, and routine blood tests and ultrasound scans were performed as part of patients' follow-up. Results and Discussion We found a higher frequency of congenital and acquired undescended testes compared with healthy children (congenital, 22% in our sample, 0.5-4% described in healthy children; acquired, 16% in our sample, 1-3% in healthy children), mostly requiring orchidopexy. No urogenital abnormalities were noted in females. Spontaneous pubertal development occurred in the majority of female and male patients with a few cases of precocious or delayed puberty; no patient presented high FSH values. Neither ADA-SCID nor treatment performed (PEG-ADA, BMT, or GT) affected pubertal development or gonadic function. Conclusion In summary, this report describes a high prevalence of cryptorchidism in a cohort of male ADA-SCID patients which could represent an additional systemic manifestation of ADA-SCID. Considering the impact urogenital and pubertal abnormalities can have on patients' quality of life, we feel it is essential to include urogenital evaluation in ADA-SCID patients to detect any

Idiopathic central precocious puberty in a Klinefelter patient: highlights on gonadotropin levels and pathophysiology

“…This suggests that gonadotropin reserve correlates with the degree of testicular destruction, which is maximal in 48,XXYY patients. This hypothesis is also supported by the description of ICPP cases in patients with Turner syndrome and cryptorchidism [5,41,42]. Indeed, the testicular destruction and/or higher estrogen levels in Klinefelter patients would increase the hypothalamic/pituitary gonadotropin reserve and explain why these patients have higher basal and GnRH-stimulated LH and FSH levels during ICPP.…”

Long-Term Immune Recovery After Hematopoietic Stem Cell Transplantation for ADA Deficiency: a Single-Center Experience

“…Patients usually present with failure to thrive and severe or recurrent opportunistic infections. Additionally, patients display typical non-immunological features, including sensorineural hearing loss [7,8], non-infectious pneumonitis, and pulmonary alveolar proteinosis [9,10], skeletal dysplasias [11][12][13][14], urogenital abnormalities [15], hepatic dysfunction [16], cognitive impairment, and behavioral abnormalities [17,18]. This variety of clinical manifestations can be explained by the metabolic pathogenesis affecting multiple organs and tissues [3].…”