Improving the efficacy of congenital adrenal hyperplasia (CaH) diagnosis in the Brazilian newborn screening (NBs) program

• Grant number: 14/07878-4
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2014
• End date: October 31, 2016
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Tania Aparecida Sartori Sanchez Bachega
• Grantee: Tania Aparecida Sartori Sanchez Bachega
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Berenice Bilharinho de Mendonça ; Daniel Fiordelisio de Carvalho ; Giselle Yuri Hayashi ; Larissa Garcia Gomes

Abstract

CAH is an autosomal recessive disease with significant morbi/mortality and high prevalence. Clinical picture may vary from the external genitalia virilization in girls, culminating with errors of sex determination, to hyponatremic dehydration and shock in the first days of life. Recently, CAH-NBS was included in 9 Brazilian states, and Nationwide coverage is scheduled until 2015. Dosing 17OH-progesterone on the filter paper (N17-OHP) is effective as the first screening test, but it results in a high frequency of false-positive (FP) and negative (FN) rates, mainly attributed to prematurity and hours of life at sample collection time, respectively. However, in the confirmation of a positive result in serum analysis, 17-OHP remains elevated in 7-17% of cases, and these newborns (NBs) must be kept in follow-up. None study evaluated different methodologies as confirmatory test in CAH-NBS in our population. Objectives: to determine the reference values of N17-OHP according to the degree of prematurity (4 groups of birth weight-BW) in samples collected before and after 72h of life. Evaluate which serum confirmatory hormonal test is the most effective by method of LC-MS/MS. Cases: approximately 100,000 NBs will be analyzed prospectively in laboratories of APAEs São Paulo and Goiás, both involved in National NBS. Methods: determination of N17-OHP reference values for routine and emergency recalls according to BW and hours of life at sample collection time. NBs with N17-OHP 2x e 99.8th percentile in the first screening test or e 99.5th in repeated screening test will be called for serum analysis of steroids (LC-MS/MS). Those with high serum 17-OHP levels will be submitted to CYP21A2 sequencing, which is the gold standard for diagnosing the disease. Expected results: optimizing the CAH diagnosis in the National NBS, especially with FP rate reduction, decreasing the program costs. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

HAYASHI, GISELLE Y.; CARVALHO, DANIEL F.; DE MIRANDA, MIRELA C.; FAURE, CLAUDIA; VALLEJOS, CARLA; BRITO, VINICIUS N.; RODRIGUES, ANDRESA DE SANTI; MADUREIRA, GUIOMAR; MENDONCA, BERENICE B.; BACHEGA, TANIA A. S. S.. Neonatal 17-hydroxyprogesterone levels adjusted according to age at sample collection and birthweight improve the efficacy of congenital adrenal hyperplasia newborn screening. CLINICAL ENDOCRINOLOGY, v. 86, n. 4, p. 8-pg., 2017-04-01. (14/07878-4)

HAYASHI, GISELLE Y.; CARVALHO, DANIEL F.; DE MIRANDA, MIRELA C.; FAURE, CLAUDIA; VALLEJOS, CARLA; BRITO, VINICIUS N.; RODRIGUES, ANDRESA DE SANTI; MADUREIRA, GUIOMAR; MENDONCA, BERENICE B.; BACHEGA, TANIA A. S. S.. Neonatal 17-hydroxyprogesterone levels adjusted according to age at sample collection and birthweight improve the efficacy of congenital adrenal hyperplasia newborn screening. Clinical Endocrinology, v. 86, n. 4, p. 480-487, APR 2017. (14/07878-4)

KAUPERT, LAURA C.; GOMES, LARISSA G.; BRITO, VINICIUS N.; LEMOS-MARINI, SOFIA H. V.; DE MELLO, MARICILDA P.; LONGUI, CARLOS A.; KOCHI, CRISTIANE; DE CASTRO, MARGARET; GUERRA, JR., GIL; MENDONCA, BERENICE B.; et al. A Single Nucleotide Variant in the Promoter Region of 17 beta-HSD Type 5 Gene Influences External Genitalia Virilization in Females with 21-Hydroxylase Deficiency. Hormone Research in Paediatrics, v. 85, n. 5, p. 333-338, 2016. (14/07878-4)

DE CARVALHO, DANIEL F.; MIRANDA, MIRELA C.; GOMES, LARISSA G.; MADUREIRA, GUIOMAR; MARCONDES, JOSE A. M.; BILLERBECK, ANA ELISA C.; RODRIGUES, ANDRESA S.; PRESTI, PAULA F.; KUPERMAN, HILTON; DAMIANI, DURVAL; et al. Molecular CYP21A2 diagnosis in 480 Brazilian patients with congenital adrenal hyperplasia before newborn screening introduction. EUROPEAN JOURNAL OF ENDOCRINOLOGY, v. 175, n. 2, p. 107-116, AUG 2016. (14/07878-4)

MOURA-MASSARI, VIVIAN OLIVEIRA; CUNHA, FLAVIA SIQUEIRA; GOMES, LARISSA GARCIA; DINIZ GOMES, DIOGO BUGANO; MIGUEL MARCONDES, JOSE ANTONIO; MADUREIRA, GUIOMAR; DE MENDONCA, BERENICE BILHARINHO; SARTORI SANCHEZ BACHEGA, TANIA A.. The Presence of Clitoromegaly in the Nonclassical Form of 21-Hydroxylase Deficiency Could Be Partially Modulated by the CAG Polymorphic Tract of the Androgen Receptor Gene. PLoS One, v. 11, n. 2, FEB 5 2016. (14/07878-4, 08/51624-6, 05/04726-0)