Corrigendum: Newborn screening for X-linked adrenoleukodystrophy in Italy: diagnostic algorithm and disease monitoring.

[This corrects the article DOI: 10.3389/fneur.2022.1072256.].

Newborn screening for X-linked adrenoleukodystrophy in Italy: Diagnostic algorithm and disease monitoring.

Introduction: X-linked adrenoleukodystrophy (X-ALD) is the most common inherited peroxisomal disorder caused by variants in the ABCD1 gene. The main phenotypes observed in men with X-ALD are primary adrenal insufficiency, adrenomyeloneuropathy, and cerebral ALD (cALD). Cerebral ALD consists of a demyelinating progressive cerebral white matter (WM) disease associated with rapid clinical decline and is fatal if left untreated. Hematopoietic stem cell transplantation is the standard treatment for cALD as it stabilizes WM degeneration when performed early in the disease. For this reason, early diagnosis is crucial, and several countries have already implemented their newborn screening programs (NBS) with the assessment of C26:0-lysophosphatidylcholine (C26:0-LPC) values as screening for X-ALD. Methods: In June 2021, an Italian group in Lombardy launched a pilot study for the implementation of X-ALD in the Italian NBS program. A three-tiered approach was adopted, and it involved quantifying the values of C26:0-LPC and other metabolites in dried blood spots with FIA-MS/MS first, followed by the more specific ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) technique and, finally, the genetic confirmation via focused NGS. Discussion: Genetically confirmed patients are set to undergo a follow-up protocol and are periodically evaluated to promptly start a specific treatment if and when the first signs of brain damage appear, as suggested by international guidelines. A specific disease monitoring protocol has been created based on literature data and personal direct experience. Conclusion: The primary aim of this study was to develop a model able to improve the early diagnosis and subsequent follow-up and timely treatment of X-ALD. Ethics: The study was approved by the local ethics committee. The research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest.

Validation of an Accurate and Noninvasive Tool to Exclude Female Precocious Puberty: Pelvic Ultrasound With Uterine Artery Pulsatility Index.

OBJECTIVE. The purpose of this study is to validate the accuracy of pelvic ultrasound (US) with the evaluation of uterine artery pulsatility index (PI) to exclude female precocious puberty. MATERIALS AND METHODS. Tanner breast development score, luteinizing hormone (LH) peak after gonadotropin-releasing hormone (GnRH) stimulation, and uterine and ovarian volumes and diameters were assessed with pelvic US in 495 girls at a single institution. The study population was divided as follows: prepubertal (n = 207), pubertal with physiologic activation of the hypothalamic-pituitary-ovarian axis (n = 176), and central precocious puberty (CPP; n = 112). PI was measured with spectral Doppler US at the ascending branches of the right uterine artery (50-Hz filter; time gain compensation, 73; pulse repetition frequency, 6.6). ROC analyses and t tests were performed. RESULTS. The mean (± SD) PI values in the prepubertal, pubertal, and CPP groups were 6.3 ± 1.4, 3.4 ± 1.1, and 4.1 ± 1.5, respectively (p < 0.001). The best PI cutoff value to distinguish pubertal from prepubertal girls was 4.6 (sensitivity, 83%; specificity, 94%; positive predictive value, 95%; negative predictive value, 80%; accuracy, 87%). ROC AUC values for LH peak (cutoff value, 5 mU/mL) and for spectral Doppler US PI plus longitudinal uterine diameter (i.e., the combination of a PI of 4.6 with a longitudinal uterine diameter of 35 mm) were 0.9272 and 0.9439, respectively (p = 0.7925). The negative predictive values for LH peak and for PI plus longitudinal uterine diameter were 89% and 88%, respectively. CONCLUSION. A PI greater than 4.6 at spectral Doppler US combined with a longitudinal uterine diameter less than 35 mm allows noninvasive exclusion of female precocious puberty with comparable accuracy and lower costs compared to examination of LH peak after GnRH stimulation. Therefore, PI plus longitudinal uterine diameter might be used as a noninvasive first-line test to exclude precocious puberty and thereby avoid further investigations.

Leydig cell tumor of the spermatic cord in an adolescent affected by congenital adrenal hyperplasia.

We report the first case of a patient with extratesticular Leydig cell tumor associated with congenital adrenal hyperplasia. An 18-year-old congenital adrenal hyperplasia patient presented with a palpable and asymptomatic right extratesticular mass. Color Doppler sonography confirmed the presence of a capsulated and vascularised lesion. Sieric tumor markers were negative. The patient underwent surgical scrotal exploration through an inguinal right incision. The mass, 18 mm in size and located within the spermatic cord, was removed and final pathology diagnosed a benign Leydig cell tumor.

46,XY karyotype in a female phenotype fetus: a challenging diagnosis.

BACKGROUND: The growing use of prenatal investigations allows an early detection of several inborn disorders, including disorders of sexual development. The management of these conditions is an arising problem. CASE: 46,XY karyotype and female phenotype were detected in a fetus; 5α-reductase and androgen receptor gene analysis on chorionic villi revealed no relevant mutation. The newborn was assigned to female sex. The diagnosis of 17ß-hydroxysteroid dehydrogenase-3 ß-OL deficiency was reached at four months of age, by means of a low testosterone/Δ 4-androstenedione ratio after HCG test and HSD17B3 gene analysis. SUMMARY AND CONCLUSION: A 46,XY fetus with female external genitalia suggests different conditions, some very rare. Specific genetic investigations should be performed prenatally when possible. A complete evaluation is mandatory after delivery to reach a correct diagnosis.