Urogenital Abnormalities in Adenosine Deaminase Deficiency.

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 abnormalities, initiate early treatment, and prevent long-term complications.

Sexual function in adult life following Passerini-Glazel feminizing genitoplasty in patients with congenital adrenal hyperplasia.

PURPOSE: We assessed external genitalia sensitivity and sexual function in adults with congenital adrenal hyperplasia who had undergone Passerini-Glazel feminizing genitoplasty as children, and compared them to a control group of healthy counterparts. MATERIALS AND METHODS: Inclusion criteria were congenital adrenal hyperplasia, Passerini-Glazel feminizing genitoplasty, adult age and penetrative vaginal intercourse. Thermal and vibratory sensitivity of the clitoris, vagina and labia minora were analyzed using the Genito Sensory Analyzer (Medoc Ltd., Minnetonka, Minnesota). Psychosexual outcome was assessed with the Beck Depression Inventory, Zung Self-Rating Anxiety Scale, Female Sexual Distress Scale and Female Sexual Function Index. Matched analyses were performed to compare outcomes in patients to controls (healthy medical students). All statistical tests were performed using SPSS®, version 18.0 RESULTS: A total of 12 patients (10%) entered the study. Thermal and vibratory clitoral sensitivity was significantly decreased in all patients compared to healthy controls (p <0.01). There was no difference in thermal or vibratory vaginal sensitivity between patients and controls. On the Female Sexual Distress Scale 11 patients (91.6%) and 11 controls (91.6%) described a stable satisfactory relationship. All patients reported active sexual desire, good arousal, adequate lubrication and orgasm. No significant difference in Female Sexual Function Index global score or single domain scores was observed between patients and controls. CONCLUSIONS: Although clitoral sensitivity in sexually active patients with congenital adrenal hyperplasia treated with Passerini-Glazel feminizing genitoplasty is significantly reduced compared to controls, sexual function in those patients is not statistically or clinically significantly different from their healthy counterparts. Finally, 1-stage Passerini-Glazel feminizing genitoplasty seems to allow normal adult sexual function.

Prenatal sonographic monitoring of idiopathic megacystis.

This case report is of a female fetus diagnosed with severe idiopathic megacystis at 21 weeks of pregnancy. Sonographic monitoring demonstrated normal amniotic fluid volume and renal structures, absence of hydronephrosis, ureteral dilation, and associated abnormalities. Conservative management was chosen with postnatal confirmation of diagnosis. The neonate presented seizures, and subsequent magnetic resonance imaging demonstrated transverse sinus thrombosis with adjacent ischemic damage. At present, the infant is 2 years old, and she is thriving normally and maintains urinary continence with spontaneous voidings.

Ovotesticular differences of sex development: male or female? Case series.

BACKGROUND: The choice of the sex of rearing in patients with ovotesticular differences of sex development (OT-DSD) is difficult. The final decision should be given by the patient himself or herself, but families' opinion is not to neglect especially when the diagnosis is precocious and the patient can't give the consent to medical or surgical procedures. How should we behave if the parents refuse to raise a child with genital ambiguity? CASE PRESENTATION: We describe and comment on our multidisciplinary approach in three patients with neonatal diagnosis of OT-DSD. The families expressed a strong desire for that which concerned the sex of rearing of their babies in contrast to the International trend of "wait and see". A specific counselling and a constant psychological support were given. CONCLUSIONS: Recent trends suggest of postponing surgery to involve the patient in the decision. Child's well-being is the goal of therapy. When medical and psychological support is not able to force parents to accept a child suffering from genital ambiguity, we think that it is better to opt for reversible medical/surgical treatments rather than allowing patients to grow up within a family that does not accept them.

Reduction of circulating neutrophils precedes and accompanies type 1 diabetes.

Human type 1 diabetes (T1D) is an autoimmune disease associated with major histocompatibility complex polymorphisms, ß-cell autoantibodies, and autoreactive T cells. However, there is increasing evidence that innate cells may also play critical roles in T1D. We aimed to monitor peripheral immune cells in early stages of T1D (i.e., in healthy autoantibody-positive subjects) and in more advanced phases of the disease (i.e., at disease onset and years after diagnosis). We found a mild but significant and reproducible peripheral neutropenia that both precedes and accompanies the onset of T1D. This reduction was not due to peripheral neutrophil cell death, impaired differentiation, or the presence of anti-neutrophil antibodies. Neutrophils were observed by electron microscopy and immunohistochemical analysis in the exocrine pancreas of multiorgan donors with T1D (both at onset and at later stages of the disease) and not in that of multiorgan donors with type 2 diabetes or nondiabetic donors. These pancreas-infiltrating neutrophils mainly localized at the level of very small blood vessels. Our findings suggest the existence of a hitherto unrecognized clinical phenotype that might reflect unexplored pathogenic pathways underlying T1D.

Passerini-glazel feminizing genitoplasty: modifications in 17 years of experience with 82 cases.

OBJECTIVES: To describe modifications of Passerini-Glazel feminizing genitoplasty and report on long-term functional outcome. METHODS: Modifications include vaginal dissection and disconnection from the urethrovaginal sinus as the initial stage of the procedure; large dissection of the neurovascular bundle on both dorsal and lateral faces of the clitoris; plication of the skin around the reduced clitoris; and suturing the lateral edge of the proximal portion of the mucocutaneous plate with the labia majora's medial edge to a plane deeper than the subcutaneous tissue. These modifications reduce bleeding and operating time, better preserve clitoral sensitivity, form the clitoral prepuce, and create labia minora. RESULTS: Eighty-two patients underwent modified Passerini-Glazel feminizing genitoplasty. Mean operating time was 120min (range: 100-180). Forty-six patients (46 of 82, 56%) were assessed at a mean follow-up of 5 yr (range: 2-9). There were no cases of clitoral vascularization defect or urethrovaginal fistula. The urethral meatus was never hypospadic. The vaginal introitus was large and elastic in all cases. Vaginal caliber at the internal suture line was as large as the vaginal introitus and the distal native vagina in 20 (43.5%) of the 46 girls. All mothers and patients reported satisfaction with external genital appearance. CONCLUSIONS: These long-term results suggest that our modifications of one-stage Passerini-Glazel feminizing genitoplasty facilitate the procedure and produce good cosmetic results.

Passerini-glazel feminizing genitoplasty: a long-term followup study.

PURPOSE: We report our experience with early 1-stage Passerini-Glazel feminizing genitoplasty with special emphasis on long-term results of vaginoplasty. MATERIALS AND METHODS: A total of 66 patients with ambiguous genitalia underwent 1-stage Passerini-Glazel feminizing genitoplasty. Long-term followup included an outpatient visit at 1 year postoperatively and a genital assessment with the patient under general anesthesia performed before menarche courses in those operated on at age 6 months to 8 years, and at 2 years postoperatively for those operated on at 9 years or older. RESULTS: All patients underwent the first long-term followup evaluation and no major complications were observed. The second long-term followup evaluation was performed in 46 patients (70%). In all cases the vaginal introitus was located in the physiological position and was large and elastic. Vaginal caliber at the suture line between the tubularized flap and vaginal mucosa was the same size as the vaginal introitus and distal native vagina in 20 of 46 patients (43%), slightly smaller in 10 (22%) and stenotic in 16 (35%). Stenosis at the suture line was corrected with simple Y-V introitoplasty performed at the same followup visit. CONCLUSIONS: Early 1-stage Passerini-Glazel feminizing genitoplasty is a safe and effective procedure that allows total surgical correction of ambiguous genitalia in infancy and good cosmetic results. Incidence of vaginal stenosis at the suture line is high but it can be repaired with simple introitoplasty performed before menarche occurs. Good functional results are presumed.