scholarly journals Reduced Frequency of Biological and Increased Frequency of Adopted Children in Males With 21-Hydroxylase Deficiency: A Swedish Population-Based National Cohort Study

2017 ◽  
Vol 102 (11) ◽  
pp. 4191-4199 ◽  
Author(s):  
Henrik Falhammar ◽  
Louise Frisén ◽  
Christina Norrby ◽  
Catarina Almqvist ◽  
Angelica Linden Hirschberg ◽  
...  
Keyword(s):  
Neonatal Screening ◽  
Population Based ◽  
Adopted Children ◽  
Hydroxylase Deficiency ◽  
Swedish Population ◽  
Salt Wasting ◽  
Reduced Frequency ◽  
Biological Children ◽  
National Cohort ◽  
21 Hydroxylase Deficiency

Abstract Context Fertility in males with 21-hydroxylase deficiency (21OHD) is unclear. Objective Study fertility outcome in males with congenital adrenal hyperplasia. Design, Setting, and Participants Males ≥15 years old with 21OHD (n = 221) were compared with controls matched for sex and year and place of birth (n = 22,024). Data were derived by linking national population-based registers. Subgroup analyses were performed regarding phenotype [salt-wasting (SW), simple virilizing (SV), and nonclassic (NC)] and CYP21A2 genotype (null, I2 splice, I172N, and P30L) and stratified by the introduction of neonatal screening. Main Outcome Measures Number of biological and adopted children. Results Males with 21OHD were less likely to be fathers of biological children [odds ratio (OR), 0.5; 95% confidence interval (CI), 0.4 to 0.7; after adjusting for socioeconomic characteristics: OR, 0.4; 95% CI, 0.2 to 0.5]. This was true for SW, SV, I2 splice, and I172N, but not for NC, null, and P30L groups (all adjusted). Among patients born before the neonatal screening introduction, fewer were fathers (adjusted OR, 0.3; 95% CI, 0.2 to 0.5), but this normalized in those born afterward. Adoption was more common in the 21OHD males (OR, 2.9; 95% CI, 1.0 to 7.9) and the SV and I172N subgroups. Age at becoming a father, marriage, region of residence, and education were similar, but fewer patients had high incomes. NC and I172N groups had, however, higher academic degrees and NC patients were more often married, whereas SW and I2 splice patients were more often divorced. Conclusions 21OHD was associated with a reduced frequency of biological children and an increased frequency of adopted children, suggesting impaired fertility, although some subgroups had normal fertility.

scholarly journals Increased Risk of Autoimmune Disorders in 21-Hydroxylase Deficiency: A Swedish Population-Based National Cohort Study

2019 ◽  
Author(s):  
Henrik Falhammar ◽  
Louise Frisén ◽  
Angelica Linden Hirschberg ◽  
Agneta Nordenskjöld ◽  
Catarina Almqvist ◽  
...  
Keyword(s):  
Cohort Study ◽  
Population Based ◽  
Autoimmune Disorders ◽  
Hydroxylase Deficiency ◽  
Swedish Population ◽  
Increased Risk ◽  
National Cohort ◽  
21 Hydroxylase Deficiency

scholarly journals Increased Cardiovascular and Metabolic Morbidity in Patients With 21-Hydroxylase Deficiency: A Swedish Population-Based National Cohort Study

2015 ◽  
Vol 100 (9) ◽  
pp. 3520-3528 ◽  
Author(s):  
Henrik Falhammar ◽  
Louise Frisén ◽  
Angelica Linden Hirschberg ◽  
Christina Norrby ◽  
Catarina Almqvist ◽  
...  
Keyword(s):  
Cohort Study ◽  
Population Based ◽  
Hydroxylase Deficiency ◽  
Swedish Population ◽  
National Cohort ◽  
21 Hydroxylase Deficiency

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.

scholarly journals Increased Prevalence of Fractures in Congenital Adrenal Hyperplasia: A Swedish Population-Based National Cohort Study

2021 ◽  
Author(s):  
Henrik Falhammar ◽  
Louise Frisén ◽  
Angelica Lindén Hirschberg ◽  
Agneta Nordenskjöld ◽  
Catarina Almqvist ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Population Based ◽  
Place Of Birth ◽  
Adrenal Hyperplasia ◽  
Mineral Density ◽  
Hydroxylase Deficiency ◽  
Swedish Population ◽  
Classic Phenotype ◽  
National Cohort ◽  
21 Hydroxylase Deficiency

Abstract Context Low bone mineral density has been reported in individuals with congenital adrenal hyperplasia (CAH), but the prevalence of fractures is unclear. Objective To study the prevalence of fractures in CAH. Design, Setting, and Participants: Patients with CAH (n=714, all 21-hydroxylase deficiency) were compared with controls matched for sex and year and place of birth (n=71,400). Data were derived by linking National Population-Based Registers. . Main Outcome Measures Number and type of fractures. Results Mean age was 29.8±18.4 years. Individuals with CAH had more fractures compared to controls (23.5% vs. 16.1%, OR 1.61, 95%CI 1.35-1.91), and this was found in both sexes (females: 19.6% vs. 13.3%, OR 1.57, 95%CI 1.23-2.02; males: 28.7% vs. 19.6%, OR 1.65, 95%CI 1.29-2.12). Fractures were significantly increased in patients born before the introduction of neonatal screening but not in those born afterwards. Any major fracture associated with osteoporosis (spine, forearm, hip or shoulder) was increased in all individuals with CAH (9.8% vs. 7.5%, OR 1.34, 95%CI 1.05-1.72). The highest prevalence of fractures was seen in SV phenotype and I172N genotype while non-classic phenotype and I2 splice genotype did not show increased prevalence. A transport accident as a car occupant and fall on the same level were more common in patients with CAH, both sexes, than in controls. Conclusions Patients with CAH had an increased prevalence of both any fracture and fractures associated with osteoporosis (both sexes) but not for patient neonatally screened. We conclude that fracture risk assessment and glucocorticoid optimization should be performed regularly.

scholarly journals SUN-LB11 What Is the Value of Clinical Suspicion in Neonatal Screening for Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency (CAH 21OHD)?

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
María Sanz Fernández ◽  
Marina Mora Sitja ◽  
Lucía L Carrascón González-Pinto ◽  
Esther González Ruiz de León ◽  
Dolores Rodríguez Arnao ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Neonatal Screening ◽  
Positive Family History ◽  
Ambiguous Genitalia ◽  
Clinical Suspicion ◽  
Hydroxylase Deficiency ◽  
Salt Wasting ◽  
Men 2 ◽  
21 Hydroxylase Deficiency ◽  
At Home

Abstract Aim: The aim of the study was to analyze the clinical suspicion and where patients were when they received the positive result of the neonatal screening for CAH 21OHD.Patients, material and methods: The present data derived from a retrospective analysis of a relatively large group of patients with classical CAH 21OHD patients nosed by newborn screening in Madrid, Spain. Results: During the period from 1990 to 2015 of this study 46 children were diagnosed with classical 21OHD [36 with the salt-wasting (SW) form and 10 with simple virilizing (SV)]. The median age at diagnosis for the patients with SW and SV form were 8,0 (6,0 - 9,0) and 18,0 (14,5 - 37,5) days respectively (P= 0,001). The disease had been suspected before the result of the newborn screening in only 11 (23,9%) patients but had not been suspected before the screening in 35 (76,1%) patients. In 11 of the patients with clinical suspicion of the disease, 8 of them were affected by SW form (1 male with a previous brother affection and 7 females, 2 of them by previous brother affected and 5 of them with ambiguous genitalia). In only 3 patients affected by SV the disease there was clinical suspicion before the result of the screening. One of them was a boy with a previous brother affected and 2 of them were females born with ambiguous genitalia. In 35 patients the disease had not been suspected before the result of the newborn screening. Twenty-eight of them were affected by SW form and 7 by SV form. Twenty five of the 28 patients with SW form were males and 4 were females (in 3 of them had been an incorrect sex assignment at born). Six of the 7 patients affected by SV form without clinical suspicion of the disease were males and 1 was female (with genitalia classificated by degree 2 according to Prader scale). The disease was suspected in 64.3% of women (9/14) and only 6.3% of men (2/32) (p<0.001).The most frequent cause of clinical suspicion of CAH 21OHD were the presence of ambiguous genitalia in women [n = 7 (63.6%), of which 5 were SW and 2 SV form) followed by positive family history [n = 4 (36, 4%), of which 3 were SW form and 1 SV form)]. When the result of Neonatal Screening was obtained 30 positive patients (65.2%) were at home without suspicion of illness, 11 (24.0%) newborns were admitted to the hospital for different reasons before the screening results were available and 5 (10.8%) patients were at home but with hospital follow-up due to clinical suspicion of illness (2 of them due to prenatal diagnosis by a previous relative, 2 women with SW form with incorrect assignment of sex at birth, labels such as men with cryptorchidism at birth and 1 woman with SV form in study by ambiguous genitalia). Conclusions: Clinical suspicion of CAH 21OHD was clearly insufficient to diagnose this severe disorder. In the majority of patients with 21OHD detected by newborn screening, the diagnosis by screening was anticipated to the clinical suspicion of the disease even in female patients with ambiguous genitalia.

scholarly journals POR polymorphisms are associated with 21 hydroxylase deficiency

2021 ◽  
Author(s):  
F. Pecori Giraldi ◽  
S. Einaudi ◽  
A. Sesta ◽  
F. Verna ◽  
M. Messina ◽  
...  
Keyword(s):  
Clinical Features ◽  
Modifier Genes ◽  
Age At Diagnosis ◽  
Adrenal Hyperplasia ◽  
Phenotype Correlation ◽  
Hydroxylase Deficiency ◽  
Salt Wasting ◽  
Control Subjects ◽  
Younger Age ◽  
21 Hydroxylase Deficiency

Abstract Purpose Genotype–phenotype correlation in congenital 21 hydroxylase deficiency is strong but by no means absolute. Indeed, clinical and hormonal features may vary among patients carrying similar CYP21A2 mutations, suggesting that modifier genes may contribute to the phenotype. Aim of the present study was to evaluate whether polymorphisms in the p450  oxidoreductase (POR) gene may affect clinical features in patients with 21 hydroxylase deficiency Methods Sequencing of the POR gene was performed in 96 patients with 21 hydroxylase deficiency (49 classic, 47 non-classic) and 43 control subjects. Results Prevalence of POR polymorphisms in patients with 21 hydroxylase was comparable to controls and known databases. The rs2228104 polymorphism was more frequently associated with non-classic vs classic 21 hydroxylase deficiency (allelic risk 7.09; 95% C.I. 1.4–29.5, p < 0.05). Classic 21 hydroxylase-deficient carriers of the minor allele in the rs2286822/rs2286823 haplotype presented more frequently the salt-wasting form (allelic risk 1.375; 95% C.I. 1.138–1.137), more severe Prader stage at birth (allelic risk 3.85; 95% C.I. 3.78–3.92), higher ACTH levels, and younger age at diagnosis. Conclusions Polymorphisms in the POR gene are associated with clinical features of 21 hydroxylase deficiency both as regards predisposition to classic vs non-classic forms and severity of classic adrenal hyperplasia.

scholarly journals Concurrence of Meningomyelocele and Salt-Wasting Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

2015 ◽  
Vol 2015 ◽  
pp. 1-4
Author(s):  
Heves Kırmızıbekmez ◽  
Rahime Gül Yesiltepe Mutlu ◽  
Serdar Moralıoğlu ◽  
Ahmet Tellioğlu ◽  
Ayşenur Cerrah Celayir
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Growth Retardation ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Salt Wasting ◽  
Significant Regression ◽  
One Year ◽  
The One ◽  
21 Hydroxylase Deficiency

Congenital adrenal hyperplasia (CAH) is a group of inherited defects of cortisol biosynthesis. A case of classical CAH due to 21-hydroxylase deficiency (21-OHD) with early onset of salt waste and concurrence of meningomyelocele (MMC) was presented here. The management of salt-wasting crisis which is complicated by a postrenal dysfunction due to neurogenic bladder was described. Possible reasons of growth retardation in the one-year follow-up period were discussed. A significant regression of the phallus with proper medical treatment was also mentioned.

scholarly journals A Case of Salt-Wasting Congenital Adrenal Hyperplasia with Triple Homozygous Mutation: Review of Literature

2020 ◽  
Author(s):  
Maria Laura Iezzi ◽  
Gaia Varriale ◽  
Luca Zagaroli ◽  
Stefania Lasorella ◽  
Marco Greco ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Autosomal Recessive ◽  
Homozygous Mutation ◽  
Adrenal Hyperplasia ◽  
Phenotype Correlation ◽  
Hydroxylase Deficiency ◽  
Autosomal Recessive Disorders ◽  
Salt Wasting ◽  
21 Hydroxylase Deficiency ◽  
Recessive Disorders

AbstractCongenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency represents a group of autosomal recessive disorders characterized by impaired cortisol production due to altered upstream steroid conversions, subclassified as classic and nonclassic forms. The genotype–phenotype correlation is possible in the most frequent case but not in all. Despite in literature many mutations are known, there is the possibility of finding a new genetic pattern in patients with CAH.

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