scholarly journals SUN-172 A False Positive Result in Newborn Screening for Congenital Adrenal Hyperplasia (CAH) in a Girl with Beckwith Wiedemann Syndrome

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Barbara Leitao Braga ◽  
Klevia N Feitosa ◽  
Thamiris Freitas Maia ◽  
Guiomar Madureira ◽  
Mirian Yumie Nishi ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Newborn Screening ◽  
False Positive ◽  
Wilms Tumor ◽  
Total Testosterone ◽  
Adrenal Hyperplasia ◽  
Chromosome 11P15 ◽  
Positive Diagnosis ◽  
False Positive Diagnosis ◽  
Increased Risk

Abstract Background: Congenital Adrenal Hyperplasia (CAH) comprises a spectrum of autosomal recessive diseases, resulting in enzymatic defects in the cortisol secretion. CAH newborn screening can avoid neonatal mortality in children with the salt-wasting form and prevent incorrect gender assignments in females. The occurrence of false-positive results creates diagnostic difficulties presenting therapeutic implications. Beckwith Wiedemann Syndrome (BWS) is a congenital disease characterized by somatic overgrowth, increased risk of neonatal hypoglycemia, and development of embryonic tumors. BWS is due to (epi)genetic changes involving growth-regulating genes with good genotype-phenotype correlation. The adrenal gland is frequently involved and may present diffuse cytomegaly of the adrenal cortex1. We reported a BWS newborn girl with a false-positive diagnosis of CAH in the screening. Case report: The patient was born at 39 weeks from an uneventful cesarean section, 5.6kg (>p97) and 52cm (>p97), referred to the Endocrinology service due to abnormal neonatal tests (neonatal 17-OHP: 96ng/mL) collected at 6 days old. At 14 days old, she was 6.3 kg (Z:+5.59), and 58cm (Z:+2.47), BMI: 18.7 kg/m2 (Z:+4.45), and with typical female external genitalia, ruling out the diagnosis of classic CAH. She presented some syndromic characteristics as macroglossia, ogival palate, orbital hypertelorism, hepatomegaly, and umbilical hernia. At 1 month and 14 days old, serum 17OHP was 7.4ng/mL, androstenedione: 6.1 ng/mL, total testosterone: 279ng/dL, 11-deoxycortisol: 2.11ng/mL, cortisol: 5.0ug/dL, and ACTH: 54pg/mL. At five months old she evolved with normalization of serum 17OHP, androstenedione and testosterone levels (1.36ng/mL, <0.50ng/mL, and 37ng/dL, respectively), but still with high DHEAS levels: 2913ng/mL. At 11 months old, DHEAS also normalized, confirming that it was transient hyperactivity of the zona reticulata. A molecular test was performed in a blood sample by MLPA, showing a gain of methylation in the imprinting control region 1 (ICR1) of chromosome 11p15, which controls two imprinted genes, H19 and IGF-2, confirming the clinical diagnosis of BWS. The hypermethylation of ICR1 is largely related to the Wilms tumor. The patient was diagnosed with bilateral Wilms tumor at 11 months old and undergone chemotherapy without adequate response requiring left nephrectomy at 1 year and 5 days old. Conclusion: We presented the first description of false-positive diagnosis of CAH in the newborn screening of a girl with Beckwith Wiedemann syndrome, probably due to a transient overactivation of the zona reticulata. References: 1.Brioude F, Kalish JM, Mussa A, Foster AC, Bliek J, Ferrero GB, et al. Expert consensus document: clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: an international consensus statement. Nat Rev Endocrinol. 2018;14(4):229-49.

scholarly journals Newborn Screening for Congenital Adrenal Hyperplasia: Review of Factors Affecting Screening Accuracy

2020 ◽  
Vol 6 (3) ◽  
pp. 67 ◽  
Author(s):  
Patrice K. Held ◽  
Ian M. Bird ◽  
Natasha L. Heather
Keyword(s):  
United States ◽  
Congenital Adrenal Hyperplasia ◽  
Newborn Screening ◽  
False Positive ◽  
Primary Care Physicians ◽  
The United States ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
21 Hydroxylase Deficiency ◽  
Screening Accuracy

Newborn screening for 21-hydroxylase deficiency (21OHD), the most common form of congenital adrenal hyperplasia, has been performed routinely in the United States and other countries for over 20 years. Screening provides the opportunity for early detection and treatment of patients with 21OHD, preventing salt-wasting crisis during the first weeks of life. However, current first-tier screening methodologies lack specificity, leading to a large number of false positive cases, and adequate sensitivity to detect all cases of classic 21OHD that would benefit from treatment. This review summarizes the pathology of 21OHD and also the key stages of fetal hypothalamic-pituitary-adrenal axis development and adrenal steroidogenesis that contribute to limitations in screening accuracy. Factors leading to both false positive and false negative results are highlighted, along with specimen collection best practices used by laboratories in the United States and worldwide. This comprehensive review provides context and insight into the limitations of newborn screening for 21OHD for laboratorians, primary care physicians, and endocrinologists.

scholarly journals Weight-adjusted neonatal 17OH-progesterone cutoff levels improve the efficiency of newborn screening for congenital adrenal hyperplasia

2011 ◽  
Vol 55 (8) ◽  
pp. 632-637 ◽  
Author(s):  
Giselle Hayashi ◽  
Cláudia Faure ◽  
Maria Fernanda Brondi ◽  
Carla Vallejos ◽  
Daiana Soares ◽  
...  
Keyword(s):  
Birth Weight ◽  
Congenital Adrenal Hyperplasia ◽  
Newborn Screening ◽  
False Positive ◽  
Low Birthweight ◽  
Adrenal Hyperplasia ◽  
Blood Samples ◽  
Term Newborns ◽  
Positive Results ◽  
Cutoff Levels

OBJECTIVE: To evaluate weight-adjusted strategy for levels of neonatal-17OHP in order to improve newborn screening (NBS) efficiency. SUBJECTS AND METHODS: Blood samples collected between 2-7 days of age from 67,640 newborns were evaluated. When N17OHP levels were > 20 ng/mL, and a second sample was requested. We retrospectively analyzed neonatal-17OHP levels measured by Auto DELFIA- B024-112 assay, grouped according to birth-weight: G1: < 1,500 g, G2: 1,501-2,000 g, G3: 2,000-2,500 g and G4: > 2,500 g. 17OHP cutoff values were determined for each group using the 97.5th, 99th, 99.5th and 99.8th percentiles. RESULTS: 0.5% of newborns presented false-positive results using the cutoff level > 20 ng/mL for all groups. Neonates of low birthweight made up 69% of this group. Seven full-term newborns presented congenital adrenal hyperplasia (CAH) and, except for one of them, 17OHP levels were > 120 ng/mL. Only the 99.8th percentile presented higher predictive positive value (2%), and lower rate of false-positives in all groups. CONCLUSIONS: We suggest the use of 99.8th percentile obtained by weight-adjusted N17OHP values of healthy newborns to reduce the rate of false-positive results in NBS.

scholarly journals 30 Predicting gestational age improves newborn screening for congenital adrenal hyperplasia

2020 ◽  
Vol 25 (Supplement_2) ◽  
pp. e11-e11
Author(s):  
Danny Jomaa ◽  
Matthew Henderson ◽  
Steven Hawken ◽  
Pranesh Chakraborty
Keyword(s):  
Positive Predictive Value ◽  
Congenital Adrenal Hyperplasia ◽  
Newborn Screening ◽  
Gestational Age ◽  
Predictive Value ◽  
False Positive ◽  
False Positive Rate ◽  
Adrenal Hyperplasia ◽  
Positive Rate ◽  
17 Hydroxyprogesterone

Abstract Background Newborn screening for congenital adrenal hyperplasia is performed using a two-tier approach. The first tier involves comparison of neonate 17-hydroxyprogesterone levels to gestational age (GA)-based thresholds. When GA is unreported, which occurs in approximately 5% of births, birth weight (BW)-based thresholds are the only available option. However, these have a lower specificity and result in more false positive results. Recently, a predictive model was developed to estimate GA based on newborn demographics and the screening analytes measured in a blood sample. Objectives The objective of this study was to determine whether supplying a predicted GA to newborns with unreported GA, and subsequent GA-based screening, has a higher positive predictive value than BW-based screening. Design/Methods Screening data was obtained for approximately 700,000 births that occurred in Canada between 2011 and 2015. Predicted GA was calculated using a model composed of demographic and screening analyte factors. The positive predictive values of BW- and predicted GA-based screening were calculated for newborns with unreported GA. A sequential approach was then developed whereby newborns with unreported GA were first screened by BW-based screening. Newborns that screened positive were then supplied with their predicted GA and screened using GA-based thresholds. Results First-tier CAH screening using GA-based 17-hydroxyprogesterone thresholds had a higher positive predictive value than using BW-based thresholds (1.30% vs. 0.82%). In the study time period, 3.61% of newborns had an unreported GA. For these newborns, predicted GA-based screening had a higher positive predictive value than BW-based screening (0.83% vs. 0.76%) and correctly identified the 2 infants with CAH whose GA was unreported. A sequential screening approach was then used: BW-based screening and, for the screen positive population, predicted GA-based screening. This further increased the positive predictive value compared to BW-based screening (0.95% vs. 0.76%), reduced the false positive rate, and correctly identified true positive cases. Conclusion Reducing the false positive rate of CAH screening is important to prevent unnecessary second-tier screening and referrals. For newborns with unreported GA (4-5% of all births), BW-based screening is the only currently available approach. However, this approach has a poor specificity and a high false positive rate compared to GA-based screening. This study is the first to demonstrate an alternative screening strategy with a higher positive predictive value for newborns with unreported GA.

Current and future perspective of newborn screening: an Indian scenario

2016 ◽  
Vol 29 (1) ◽  
Author(s):  
Gurjit Kaur ◽  
Kiran Thakur ◽  
Sandeep Kataria ◽  
Teg Rabab Singh ◽  
Bir Singh Chavan ◽  
...  
Keyword(s):  
Health Care ◽  
Congenital Adrenal Hyperplasia ◽  
Newborn Screening ◽  
Health Care System ◽  
Congenital Hypothyroidism ◽  
G6pd Deficiency ◽  
Metabolic Disorders ◽  
Adrenal Hyperplasia ◽  
Screening Programs ◽  
Care System

AbstractNewborn screening comprises a paramount public health program seeking timely detection, diagnosis, and intervention for genetic disorders that may otherwise produce serious clinical consequences. Today newborn screening is part of the health care system of developed countries, whereas in India, newborn screening is still in the toddler stage.We searched PubMed with the keywords newborn screening for metabolic disorders, newborn screening in India, and congenital disorder in neonates, and selected publications that seem appropriate.In India, in spite of the high birth rate and high frequency of metabolic disorders, newborn screening programs are not part of the health care system. At Union Territory, Chandigarh in 2007, newborn screening was initiated and is currently ongoing for three disorders, that is, congenital hypothyroidism, congenital adrenal hyperplasia, and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Prevalence of these disorders is found to be 1:1400 for congenital hypothyroidism, 1:6334 for congenital adrenal hyperplasia, and 1:80 for G6PD deficiency.Mandatory newborn screening for congenital hypothyroidism should be implemented in India, and other disorders can be added in the screening panel on the basis of region-wise prevalence. The objective of this review is to provide insight toward present scenario of newborn screening in India along with recommendations to combat the hurdles in the pathway of mandatory newborn screening.

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