scholarly journals Thirty-Year Lessons from the Newborn Screening for Congenital Adrenal Hyperplasia (CAH) in Japan

2021 ◽  
Vol 7 (3) ◽  
pp. 36
Author(s):  
Atsumi Tsuji-Hosokawa ◽  
Kenichi Kashimada
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Newborn Screening ◽  
Screening Program ◽  
Adrenal Crisis ◽  
Screening System ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
The Past ◽  
Life Threatening ◽  
21 Hydroxylase Deficiency

Congenital adrenal hyperplasia (CAH) is an inherited disorder caused by the absence or severely impaired activity of steroidogenic enzymes involved in cortisol biosynthesis. More than 90% of cases result from 21-hydroxylase deficiency (21OHD). To prevent life-threatening adrenal crisis and to help perform appropriate sex assignments for affected female patients, newborn screening (NBS) programs for the classical form of CAH have been introduced in numerous countries. In Japan, the NBS for CAH was introduced in 1989, following the screenings for phenylketonuria and congenital hypothyroidism. In this review, we aim to summarize the experience of the past 30 years of the NBS for CAH in Japan, composed of four parts, 1: screening system in Japan, 2: the clinical outcomes for the patients with CAH, 3: various factors that would impact the NBS system, including timeline, false positive, and LC-MS/MS, 4: Database composition and improvement of the screening program.

scholarly journals MON-158 Rates of Illnesses in Patients with Congenital Adrenal Hyperplasia

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Ashwini Mallappa ◽  
Ninet Sinaii ◽  
Diala El-Maouche ◽  
Padmasree Veeraraghavan ◽  
Elizabeth Joyal ◽  
...  
Keyword(s):  
At Risk ◽  
Congenital Adrenal Hyperplasia ◽  
Incidence Rate ◽  
Adrenal Crisis ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Life Threatening ◽  
Tract Infections ◽  
21 Hydroxylase Deficiency ◽  
Stress Dose

Abstract Background: Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is the most common cause of primary adrenal insufficiency during childhood and patients are at risk for life-threatening adrenal crisis. In a recent study from our group, we reported gastrointestinal and upper respiratory tract infections as the two most common precipitating events for adrenal crises and hospitalizations across all ages. We also reported 11 incidents of life-threatening hypoglycemic events in children, sometimes accompanied by seizures. Objective: To evaluate the annual rates of illnesses in patients with CAH. Methods: We retrospectively reviewed longitudinally collected data over 23 years from 156 CAH patients enrolled in our CAH natural history study (www.clinicaltrials.gov #NCT00250159). Incidence of illnesses and occurrence of stress-dose days were computed per person-years. Incidence rate ratio (IRR) with 95% confidence intervals (CI) were calculated for comparisons. Results: A total of 2298 visits (1909 for children and 389 for adults) were available for evaluation among the 156 patients (21-OHD: 97.4%). A total of 1870 illness events (1664 in children) were observed in 143 patients (121 children) and 2710 stress-dose days (2460 in children) were observed in 141 patients (120 children) during the study period. The incidence rate of illnesses was higher in children than adults (1.5 vs. 0.5 illnesses/person-years, IRR = 3.1, 95% CI 2.7 - 3.6; P<.0001) with incidence highest in young patients: 2.5 illnesses/person-years in <3 year olds. Similarly, the stress-dose days were higher in children than adults (2.2 vs. 0.6 days/person-years, IRR = 3.8, 95% CI 3.3 - 4.3; P<.0001). Conclusions: Patients with CAH do not appear to have higher rates of infectious illnesses than expected, but remain at risk for life-threatening adrenal crises. As expected, illness rates are higher during childhood than adulthood. Prevention of adrenal crisis is crucial and is best accomplished through repeated age-specific education of patients and caregivers. Acknowledgement: This research was supported by the Intramural Research Program at the National Institutes of Health (NIH), Bethesda, Maryland.

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.

Presenting status of children with classical congenital adrenal hyperplasia over two decades (1999–2018) in the absence of newborn screening in Sri Lanka

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Sumudu N. Seneviratne ◽  
Udara Sandakelum ◽  
Chaminda H. Jayawardena ◽  
Ashangi M. Weerasinghe ◽  
Piyumi S. Wickramarachchi ◽  
...  
Keyword(s):  
Sri Lanka ◽  
Congenital Adrenal Hyperplasia ◽  
Newborn Screening ◽  
Initial Presentation ◽  
Adrenal Crisis ◽  
Adrenal Hyperplasia ◽  
Severe Hyponatremia ◽  
The Past ◽  
Childhood Morbidity ◽  
Gender Based

Abstract Objectives Although new-born screening (NBS) for classical congenital adrenal hyperplasia (C-CAH) has been available for decades, it is not widely implemented. We assessed the usefulness of introducing NBS for C-CAH, by analyzing presenting status of infants with C-CAH, over the past two decades, in Sri Lanka. Methods This retrospective clinic-based study, from the largest tertiary children’s hospital in Sri Lanka, analyzed initial presenting features of children with C-CAH from 1999 to 2018, in the absence of NBS for CAH, and included gender-based comparisons. Results Features suggestive of impending adrenal-crisis were seen at initial presentation in >80 % (dehydration 70%, hyponatremia 65%, hyperkalemia 47%, vomiting 45%, hypoglycemia 22%, collapse 20%). Hyperpigmentation was seen in 78%, and consanguinity in 27%. There were fewer affected males (n = 12) compared to females (n = 28). Most girls (96%) had virilized genitalia, and 16 faced uncertainty about gender at birth. Median age at diagnosis was 20 days. More than 70% of children had SW-CAH (males = 9 and females = 20). There were fewer males with SW-CAH, and all had features of impending adrenal crisis, including severe hyponatremia in 50%, while 62% of girls also developed hyponatremia and 33% had hyperkalemia, prior to treatment. Treatment of SW-CAH was initiated at a median age of 30 days in boys, and 10 days of age in girls. Conclusion Many boys and girls with C-CAH from Sri Lanka presented late with impending adrenal crisis. Males were diagnosed later, and some possibly succumbed to C-CAH undiagnosed. These findings support including CAH in NBS programs to avert preventable childhood morbidity and mortality.

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.

A neonatal mass-screening for congenital adrenal hyperplasia in Japan

1984 ◽  
Vol 107 (4) ◽  
pp. 513-518 ◽  
Author(s):  
Kazuhiko Shimozawa ◽  
Sumitaka Saisho ◽  
Nobuchika Saito ◽  
Jun-ichi Yata ◽  
Yoshio Igarashi ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Mass Screening ◽  
Screening Program ◽  
Clinical Signs ◽  
Plasma Sodium ◽  
Adrenal Hyperplasia ◽  
Perinatal Complications ◽  
Hydroxylase Deficiency ◽  
Urine Metabolites ◽  
21 Hydroxylase Deficiency

Abstract. A pilot neonatal mass-screening for congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) was performed in the western region of Shizuoka Prefecture, Japan, using a simplified radioimmunoassay method for 'Disc-17-hydroxyprogesterone (17-OHP)' determination. The results obtained during a 30-month period indicated that 3 infants out of the 34314 neonates examined were proved to have 21-OHD, and the incidence of homozygotes and heterozygotes were estimated to be 1:11438 and 1:54, respectively. At the time of recall, the concentrations of plasma 17-OHP and 21-deoxycortisol and their urine metabolites as well as plasma sodium levels were quite applicable to diagnosis, while the clinical signs that may be manifest in 21-OHD were of little value in this connection. Prematurity and perinatal complications of neonates tended to give false-positive results, being secondary to the function of the residual foetal adrenal cortex and non-specific stimulatory effects of various stresses. Despite several technical and practical problems to be solved, the present study demonstrated the importance and validity of a neonatal mass-screening program for CAH.

scholarly journals Increased Mortality in Patients With Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

2014 ◽  
Vol 99 (12) ◽  
pp. E2715-E2721 ◽  
Author(s):  
Henrik Falhammar ◽  
Louise Frisén ◽  
Christina Norrby ◽  
Angelica Lindén Hirschberg ◽  
Catarina Almqvist ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Neonatal Screening ◽  
Causes Of Death ◽  
Population Based ◽  
Personal Identification ◽  
Adrenal Crisis ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Salt Wasting ◽  
21 Hydroxylase Deficiency

Context: Reports on mortality in patients with congenital adrenal hyperplasia (CAH) are lacking. Objective: This study sought to study mortality and causes of death in CAH. Design, Setting, and Participants: We studied patients with CAH (21-hydroxylase deficiency, n = 588; CYP21A2 mutations known, >80%), and compared them with controls (n = 58 800). Data were derived through linkage of national population-based registers. Main Outcome Measures: Mortality and causes of death. Results: Mean age of death was 41.2 ± 26.9 years in patients with CAH and 47.7 ± 27.7 years in controls (P < .001). Among patients with CAH, 23 (3.9%) had deceased compared with 942 (1.6%) of controls. The hazard ratio (and 95% confidence interval) of death was 2.3 (1.2–4.3) in CAH males and 3.5 (2.0–6.0) in CAH females. Including only patients born 1952–2009, gave similar total results but only patients with salt wasting (SW) or with unclear phenotype had an increased mortality. The causes of death in patients with CAH were adrenal crisis (42%), cardiovascular (32%), cancer (16%), and suicide (10%). There were seven additional deaths in CAH individuals with incomplete or reused personal identification number that could not be analyzed using linkage of registers. Of the latter, all except one were deceased before the introduction of neonatal screening in 1986, and most of them in the first weeks of life, probably in an adrenal crisis. Conclusions: CAH is a potentially lethal condition and was associated with excess mortality due to adrenal crisis. The SW phenotype also seemed to have worse outcome in children and adults due to adrenal crisis and not only before the introduction of neonatal screening.

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