High frequency of non-classical congenital adrenal hyperplasia form among children with persistently elevated levels of 17-hydroxyprogesterone after newborn screening
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Patrícia S. Castro
Abstract
Background
Early diagnosis after newborn screening (NBS) for congenital adrenal hyperplasia (CAH) allows proper treatment, reducing mortality rates and preventing development of hyperandrogenic manifestations and incorrect sex assignment at birth. Despite the high NBS sensitivity to detect CAH classical forms, one of the main issues is identifying asymptomatic children who remained with increased 17-hydroxyprogesterone (17-OHP) levels. In this study, we aimed to contribute to understanding the diagnosis of these children.
Methods
Children with increased serum 17-OHP levels, and without disease-related clinical features during follow-up, underwent the entire CYP21A2 gene sequencing and multiplex ligation-dependent probe amplification (MLPA) analysis (SALSA MLPA P050B CAH). Patients’ genotypes were subsequently sorted as compatible with CAH disease, and children were evaluated to determine the clinical status.
Results
During the study period, 106,476 newborns underwent CAH NBS. During follow-up, 328 children (0.3%) were identified as having false-positive tests and 295 were discharged after presenting with 17-OHP levels within reference values. Thirty-three remained asymptomatic and with increased serum 17-OHP levels after a mean follow-up of 3.4 years, and were subjected to molecular analysis. Seventeen out of the 33 children carried mutations: seven in the heterozygous state, nine carried non-classical genotypes and the remaining child carried a classical genotype.
Conclusions
We found a high frequency of non-classical CAH (NCCAH) diagnosis among children with persistent elevation of 17-OHP levels. Our findings support molecular study as decisive for elucidating diagnosis in these asymptomatic children. Molecular analysis as a confirmatory test is relevant to guide their follow-up, allows genetic counseling and avoids over treating NCCAH form.
Acknowledgments
We thank the newborn screening team and the staff of NUPAD, MG, for their support.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: The research was partially supported by Núcleo de Ações e Pesquisa em Apoio Diagnóstico da Faculdade de Medicina da UFMG (NUPAD), MG-Brazil.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
Declaration of conflict of interest: There are no potential conflicts of interest relevant to this article.
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©2019 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Reviews
- Using height-corrected definition of metabolic syndrome in children and adolescents
- Association between early antibiotic exposure and risk of childhood weight gain and obesity: a systematic review and meta-analysis
- Original Articles
- Carbonated beverage consumption is associated with lower C-peptide in adolescents
- Low levels of cardiorespiratory fitness and abdominal resistance are associated with metabolic risk in schoolchildren
- Effect of metformin on clinical and biochemical hyperandrogenism in adolescent girls with type 1 diabetes
- Obesity-related thyroiditis in childhood: relationship with insulin resistance
- An isolated Xp deletion is linked to autoimmune diseases in Turner syndrome
- Non-invasive assessment of aortic stiffness and blood pressure in young Turner syndrome patients
- High frequency of non-classical congenital adrenal hyperplasia form among children with persistently elevated levels of 17-hydroxyprogesterone after newborn screening
- The “combined team” transition clinic model in endocrinology results in high adherence rates and patient satisfaction
- Utilizing health information technology to improve the recognition and management of life-threatening adrenal crisis in the pediatric emergency department: medical alert identification in the 21st century
- Testicular adrenal rest tumors in patients with congenital adrenal hyperplasia: 6 years of follow-up
- Letter to the Editor
- Growth failure in infancy and early adiposity rebound
- Short Communication
- Clinical utility of stimulation tests in infants with suspected adrenal insufficiency (AI)
- Case Reports
- Two siblings with Gaucher type 3c: different clinical presentations
- Acquired partial lipodystrophy with metabolic disease in children following hematopoietic stem cell transplantation: a report of two cases and a review of the literature
- Therapeutic challenges in a patient with the simple virilizing (SV) form of congenital adrenal hyperplasia (CAH) due to the P30L/I172N genotype
Articles in the same Issue
- Frontmatter
- Reviews
- Using height-corrected definition of metabolic syndrome in children and adolescents
- Association between early antibiotic exposure and risk of childhood weight gain and obesity: a systematic review and meta-analysis
- Original Articles
- Carbonated beverage consumption is associated with lower C-peptide in adolescents
- Low levels of cardiorespiratory fitness and abdominal resistance are associated with metabolic risk in schoolchildren
- Effect of metformin on clinical and biochemical hyperandrogenism in adolescent girls with type 1 diabetes
- Obesity-related thyroiditis in childhood: relationship with insulin resistance
- An isolated Xp deletion is linked to autoimmune diseases in Turner syndrome
- Non-invasive assessment of aortic stiffness and blood pressure in young Turner syndrome patients
- High frequency of non-classical congenital adrenal hyperplasia form among children with persistently elevated levels of 17-hydroxyprogesterone after newborn screening
- The “combined team” transition clinic model in endocrinology results in high adherence rates and patient satisfaction
- Utilizing health information technology to improve the recognition and management of life-threatening adrenal crisis in the pediatric emergency department: medical alert identification in the 21st century
- Testicular adrenal rest tumors in patients with congenital adrenal hyperplasia: 6 years of follow-up
- Letter to the Editor
- Growth failure in infancy and early adiposity rebound
- Short Communication
- Clinical utility of stimulation tests in infants with suspected adrenal insufficiency (AI)
- Case Reports
- Two siblings with Gaucher type 3c: different clinical presentations
- Acquired partial lipodystrophy with metabolic disease in children following hematopoietic stem cell transplantation: a report of two cases and a review of the literature
- Therapeutic challenges in a patient with the simple virilizing (SV) form of congenital adrenal hyperplasia (CAH) due to the P30L/I172N genotype
