Typical characteristics of children with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency: a single-centre experience and review of the literature

2019 ◽  
Vol 32 (3) ◽  
pp. 259-267 ◽  
Author(s):  
Thomas Breil ◽  
Vira Yakovenko ◽  
Ioana Inta ◽  
Daniela Choukair ◽  
Daniela Klose ◽  
...  
Keyword(s):  
Arterial Hypertension ◽  
Congenital Adrenal Hyperplasia ◽  
Newborn Screening ◽  
Tall Stature ◽  
Adrenal Hyperplasia ◽  
Single Centre ◽  
Hydroxylase Deficiency ◽  
Precocious Pseudopuberty ◽  
Male Patients ◽  
21 Hydroxylase Deficiency

Abstract Background 11β-hydroxylase deficiency (11βOHD) is a rare disease representing the second most common cause of congenital adrenal hyperplasia (CAH) (5–8%) with an incidence of about 1:100,000. In contrast to 21-hydroxylase deficiency (21OHD), 11βOHD is not included in neonatal screening programmes. The objective of this study was to demonstrate the typical features of male patients with 11βOHD. Methods Clinical, biochemical and radiological data of patients with 11βOHD were analysed in this retrospective single-centre analysis. Results Six male patients of four unrelated families with 11βOHD were identified (0.1–13.5 years of chronological age [CA] at diagnosis). The predominant symptoms were arterial hypertension, tall stature and precocious pseudopuberty. Bone ages (BAs) were remarkably advanced at diagnosis in four index patients (median difference BA–CA: 5.5 years, range 1.5–9.2 years). Homozygous mutations were identified in exon 7 (c.1179_1180dupGA [p.Asn394Argfs*37]) and exon 8 (c.1398+2T>C) of the CYP11B1 gene leading both to a complete loss of function. The latter mutation has not yet been described in databases. 11βOHD was identified by the measurement of 11-deoxycortisol in a newborn screening card of one patient retrospectively. Testicular adrenal rest tumours (TARTs) were detected in three patients at 3.7 years, 11 years and 14.4 years. Conclusion The diagnosis of CAH due to 11βOHD is delayed and should be suspected in children with arterial hypertension, tall stature and precocious pseudopuberty. Patients may develop TARTs as early as infancy. 11βOHD should be included in newborn screening programmes, at least in newborns of index families, to allow early diagnosis and the start of treatment to reduce morbidity.

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 Sexuality in Males With Congenital Adrenal Hyperplasia Resulting From 21-Hydroxylase Deficiency

2019 ◽  
Vol 3 (8) ◽  
pp. 1445-1456 ◽  
Author(s):  
Katharina Gehrmann ◽  
Manon Engels ◽  
Elena Bennecke ◽  
Claire Bouvattier ◽  
Henrik Falhammar ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Sexual Activity ◽  
Sexual Problems ◽  
Psychological Problems ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Psychological Issues ◽  
Key Factor ◽  
Male Patients ◽  
21 Hydroxylase Deficiency

Abstract Purpose Although sexuality has been reported to be impaired in females with congenital adrenal hyperplasia (CAH) resulting from 21-hydroxylase deficiency, sexuality in males with CAH so far has remained largely unconsidered. Patients One of the largest European male cohorts of patients with CAH in which sexuality in male patients with CAH was assessed. Methods Sexuality was evaluated in 91 sexually active male patients with CAH using questionnaires investigating sexual orientation, age at sexual initiation, sexual activity, satisfaction with sex life, and sexual problems, such as fears or dislike of sexual activity, lack or excessive sexual desire, difficulties getting aroused or reaching an orgasm, premature ejaculation, and no or incomplete erection. Results Sexuality in male patients with CAH was similar to European reference populations. If sexuality problems were present, they were less frequently reported by the most severely affected CAH males. Adducing a holistic perspective, sexual problems showed substantial association to psychological problems, such as anxiety and depression. Conclusions Sexuality in male patients with CAH in general was unaffected and sexuality problems seemed to be associated in particular with psychological problems. Because sexual health is a key factor of general health, we recommend that sexuality as well as psychological issues explicitly should be addressed in health care of patients with a CAH diagnosis, independent of sex.

scholarly journals Case Report: Infant With Congenital Adrenal Hyperplasia and 47,XXY

2022 ◽  
Vol 12 ◽  
Author(s):  
Sophia Q. Song ◽  
Andrea Gropman ◽  
Robert W. Benjamin ◽  
Francie Mitchell ◽  
Michaela R. Brooks ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Genetic Disorders ◽  
Gene Mutations ◽  
Tall Stature ◽  
Clinical Report ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Autosomal Recessive Disorders ◽  
21 Hydroxylase Deficiency ◽  
Recessive Disorders

Congenital adrenal hyperplasia is a group of autosomal recessive disorders in which enzymes in the cortisol biosynthesis pathways are disrupted by gene mutations. The most common form of congenital adrenal hyperplasia, caused by 21-hydroxylase deficiency, is characterized by decreased cortisol and aldosterone synthesis and excessive androgen production. Adult height is often compromised in affected patients. Intellectual capability remains intact in patients with congenital adrenal hyperplasia caused by 21-hydroxylase deficiency, based on previous studies. 47,XXY (KS) is a sex chromosomal aneuploidy that manifests with hypergonadotropic hypogonadism, tall stature, and variable intellectual and behavioral dysfunction. This clinical report describes an infant with 21-hydroxylase deficiency congenital adrenal hyperplasia and 47,XXY. The results of his neurodevelopmental, endocrine, neurological, and physical therapy evaluations during his first 22 months are included and were normal. This is the first published case investigating the neurodevelopmental profile of a patient with the combination of these two genetic disorders.

scholarly journals Congenital Adrenal Hyperplasia: Time to Replace 17OHP with 21-Deoxycortisol

2019 ◽  
Vol 91 (6) ◽  
pp. 416-420 ◽  
Author(s):  
Walter L. Miller
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Newborn Screening ◽  
Premature Infants ◽  
Specific Marker ◽  
Fetal Life ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Androgen Excess ◽  
Screening Programs ◽  
21 Hydroxylase Deficiency

Congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency (21OHD) has a worldwide incidence of 1 in 15–20,000. Affected individuals have adrenal insufficiency and androgen excess; the androgen excess begins during fetal life, typically resulting in 46,XX disordered sexual development. In 21OHD, 17-hydroxyprogesterone (17OHP), the steroid proximal to 21-hydroxylase, accumulates. Most industrialized countries have newborn screening programs that measure 17OHP; such screening has permitted rapid detection of newborns with 21OHD, saving lives previously lost to mineralocorticoid deficiency and salt wasting. However, newborn screening is plagued by false positives. 17OHP is above most “cutoff values” in the first 24 h of life, is high in otherwise normal premature infants, and in many term infants with physiologic stress from unrelated diseases. In addition, newborn 17OHP may be elevated in other forms of CAH, including 11-hydroxylase deficiency, 3β-hydroxysteroid dehydrogenase deficiency, and P450 oxidoreductase deficiency. In 21OHD, some of the accumulated intra-adrenal 17OHP is converted to 21-deoxycortisol (21-deoxy) by 11β-hydroxylase (CYP11B1); 21-deoxy is not elevated in premature infants or in other forms of CAH, and hence is a more specific marker for 21OHD. However, 21-deoxy assays have not been generally available until recently, hence experience is limited. We urge clinical investigators, commercial reference laboratories, and newborn screening programs to investigate replacing 17OHP with 21-deoxy as the analyte of choice for studies of 21OHD.

scholarly journals Challenges in Assessing the Cost-Effectiveness of Newborn Screening: The Example of Congenital Adrenal Hyperplasia

2020 ◽  
Vol 6 (4) ◽  
pp. 82
Author(s):  
Scott D. Grosse ◽  
Guy Van Vliet
Keyword(s):  
Cost Effectiveness ◽  
Congenital Adrenal Hyperplasia ◽  
Newborn Screening ◽  
Economic Evaluations ◽  
Test Case ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Data Limitations ◽  
21 Hydroxylase Deficiency ◽  
The Cost

Generalizing about the cost-effectiveness of newborn screening (NBS) is difficult due to the heterogeneity of disorders included in NBS panels, along with data limitations. Furthermore, it is unclear to what extent evidence about cost-effectiveness should influence decisions to screen for specific disorders. Screening newborns for congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency can serve as a useful test case, since there is no global consensus on whether CAH should be part of NBS panels. Published and unpublished cost-effectiveness analyses of CAH screening have yielded mixed findings, largely due to differences in methods and data sources for estimating health outcomes and associated costs of early versus late diagnosis as well as between-country differences. Understanding these methodological challenges can help inform future analyses and could also help interested policymakers interpret the results of economic evaluations.

A pilot study on newborn screening for congenital adrenal hyperplasia in Beijing

2019 ◽  
Vol 32 (3) ◽  
pp. 253-258 ◽  
Author(s):  
Li-fei Gong ◽  
Xiao Gao ◽  
Nan Yang ◽  
Jin-qi Zhao ◽  
Hai-he Yang ◽  
...  
Keyword(s):  
Pilot Study ◽  
Congenital Adrenal Hyperplasia ◽  
Newborn Screening ◽  
Clinical Characteristics ◽  
Skin Pigmentation ◽  
Clinical Signs ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Feeding Difficulties ◽  
21 Hydroxylase Deficiency

Abstract Background A provisionary screening programme for 21-hydroxylase deficiency (21-OHD) was initiated in Beijing in 2014. The aim of this study was to investigate the incidence and the associated clinical characteristics of neonatal congenital adrenal hyperplasia (CAH) in Beijing and to provide evidence-based guidance for its application in CAH screening. Methods Live birth newborns (n=44,360) were screened for CAH in Beijing from July 2014 to April 2018. The levels of 17-hydroxyprogesterone (17-OHP) in the blood were estimated using the time-resolved fluoroimmunoassay. Neonates with a positive result and a level >30 nmol/L of 17-OHP were called for a retest. CAH was diagnosed based on further laboratory findings combined with clinical signs, such as weight loss, feeding difficulties, skin pigmentation, and atypical genitalia. Through a review of medical records, the clinical findings including molecular data were reported. Results Of the 44,360 neonates screened, 280 cases were deemed positive. Of these, 203 neonates were recalled for further tests and six patients (three boys and three girls) were diagnosed with CAH. Five cases of classic salt-wasting and one case of simple virilising 21-OHD were identified. The incidence of CAH in Beijing was 1:7393. The most frequent 21-OHD mutation was c.293-13C/A>G. Conclusions The incidence of CAH in Beijing was higher than the national average. The results support the need for neonatal CAH screening in Beijing. This pilot study demonstrates the clinical characteristics of 21-OHD through newborn screening. Early detection and treatment through neonatal screening may reduce mortality rates and optimise developmental outcomes.

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