scholarly journals Aldosterone signaling defect in young infants: single-center report and review

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Melati Wijaya ◽  
Huamei Ma ◽  
Jun Zhang ◽  
Minlian Du ◽  
Yanhong Li ◽  
...  
Keyword(s):  
Clinical Picture ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Homozygous Mutation ◽  
Hydroxylase Deficiency ◽  
Salt Wasting ◽  
Young Infants ◽  
Adrenal Imaging ◽  
Compound Heterozygous Mutations ◽  
21 Hydroxylase Deficiency

Abstract Background Aldosterone (Ald) is a crucial factor in maintaining electrolyte and water homeostasis. Defect in either its synthesis or function causes salt wasting (SW) manifestation. This disease group is rare, while most reported cases are sporadic. This study aimed to obtain an overview of the etiology and clinical picture of patients with the above condition and report our rare cases. Methods A combination of retrospective review and case studies was conducted at the Pediatric Endocrine unit of The First Affiliated Hospital Sun Yat Sen University from September 1989 to June 2020. Results A total of 187 patients with SW were enrolled, of which 90.4% (n = 169) were diagnosed with congenital adrenal hyperplasia (CAH). SW type 21-hydroxylase deficiency accounted for 98.8% (n = 167) of CAH diagnosis, while 1.2% (n = 2) was of lipoid CAH. Non-CAH comprised 9.6% (n = 18) of the total patients whose etiologies included SF-1 gene mutation (n = 1), X-linked adrenal hypoplasia congenita (n = 9), aldosterone synthase deficiency (ASD, n = 4), and pseudo-hypoaldosteronism type 1 (PHA1, n = 1). Etiologies were not identified in three patients. All of patients with ASD and PHA1 exhibited SW syndrome in their early neonatal period. DNA sequencing showed mutations of CYP11B2 for P1-P4 and NR3C2 for P5. P1 and P2 were sibling brothers affected by compound heterozygous mutations of c.1121G > A (p.R374Q) and c.1486delC p.(L496fs); likewise, P4 was identified with compound heterozygous mutations of c.1200 + 1G > A and c.240–1 G > T; meanwhile P3 demonstrated c.1303G > A p.(G435S) homozygous mutation in CYP11B2 gene. Lastly, P5 showed c.1768 C > T p.(R590*) heterozygous mutation in the NR3C2 gene. Conclusion Etiology of infant with aldosterone defect was mostly congenital. Renal and adrenal imaging are recommended to exclude renal causes. If clinical picture is suggestive, normal plasma Ald in early infancy cannot rule out aldosterone insufficiency.

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.

scholarly journals Predicting Phenotype in Steroid 21-Hydroxylase Deficiency? Comprehensive Genotyping in 155 Unrelated, Well Defined Patients from Southern Germany

2000 ◽  
Vol 85 (3) ◽  
pp. 1059-1065 ◽  
Author(s):  
Nils Krone ◽  
Andreas Braun ◽  
Adelbert Anton Roscher ◽  
Dietrich Knorr ◽  
Hans Peter Schwarz
Keyword(s):  
Splice Site ◽  
Splice Site Mutation ◽  
Compound Heterozygous ◽  
Site Mutation ◽  
Hydroxylase Deficiency ◽  
Salt Wasting ◽  
Severe Mutation ◽  
Heterozygous Form ◽  
21 Hydroxylase Deficiency ◽  
Intron 2

Abstract Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders. CAH is most often caused by deficiency of steroid 21-hydroxylase. The frequency of CYP21-inactivating mutations and the genotype-phenotype relationship were characterized in 155 well defined unrelated CAH patients. We were able to elucidate 306 of 310 disease-causing alleles (diagnostic sensitivity, 98.7%). The most frequent mutation was the intron 2 splice site mutation (30.3%), followed by gene deletions (20.3%), the I172N mutation (19.7%) and large gene conversions (7.1%). Five point mutations were detected that have not been described in other CAH cohorts. Genotypes were categorized in 4 mutation groups (null, A, B, and C) according to their predicted functional consequences and compared to the clinical phenotype. The positive predictive value for null mutations (ppvnull) was 100%, as all patients with these mutations had a salt-wasting phenotype. In mutation group A (intron 2 splice site mutation in homozygous or heterozygous form with a null mutation), the ppvA to manifest with salt-wasting CAH was 90%. In group B predicted to result in simple virilizing CAH (I172N in homozygous or compound heterozygous form with a more severe mutation), ppvB was 74%. In group C (P30L, V281L, P453S in homozygous or compound heterozygous form with a more severe mutation), ppvC was 64.7% to exhibit the nonclassical form of CAH, but 90% when excluding the P30L mutation. Thus, in general, a good genotype-phenotype relationship is shown in patients with either the severest or the mildest mutations. A considerable degree of divergence is observed within mutation groups of intermediate severity. As yet undefined factors modifying 21-hydroxylase gene expression and steroid hormone action are likely to account for these differences in phenotypic expression.

Vaginal bleeding and a giant ovarian cyst in an infant with 21-hydroxylase deficiency

2018 ◽  
Vol 31 (2) ◽  
pp. 229-233 ◽  
Author(s):  
Nursel Muratoğlu Şahin ◽  
Elvan Bayramoğlu ◽  
Semra Çetinkaya ◽  
Şenay Şavaş Erdeve ◽  
Ayşe Karaman ◽  
...  
Keyword(s):  
Vaginal Bleeding ◽  
Ambiguous Genitalia ◽  
Ovarian Cysts ◽  
Homozygous Mutation ◽  
Adrenal Androgen ◽  
Hydroxylase Deficiency ◽  
Glucocorticoid Treatment ◽  
Salt Wasting ◽  
Laboratory Test Results ◽  
21 Hydroxylase Deficiency

Abstract Background: Increased adrenal androgen hormones in congenital adrenal hyperplasia (CAH) can rarely cause giant ovarian cysts in the neonatal period. Although the exact mechanism of the development of ovarian cysts is unknown, it is thought that increased androgen levels stimulate folicle development by increasing follicle stimulating hormone (FSH) levels. Case presentation: A 16-day-old newborn with ambiguous genitalia was presented to our clinic. Laboratory test results were as follows: sodium: 126 mEq/L, potassium: 5.4 mEq/L, renin: 132 pg/mL, adrenocorticotropic hormone (ACTH): 207 pg/mL, cortisole: 7.8 μg/dL, basal 17OH progesterone: 21 ng/mL, androstenedione: 5.1 ng/mL, testosterone: 1188 ng/dL and dehydroepiandrosterone sulfate (DHEAS)>1500 μg/dL. Karyotype analysis resulted in 46,XX. A homozygous mutation of R356W was detected in the CYP21A2 gene. The classical severe form of salt wasting 21 hydroxylase deficiency was diagnosed and treatment was started with hydrocortisone and fludrocortisone. Good metabolic control was ensured by monthly visits but the baby presented with vaginal bleeding as soiling at 4 months. The cystic lesion which extended to the epigastric area from the pelvis in the midline abdomen, had a size of 90×80×60 mm and medially, thin ovarian parenchyma was detected in ultrasonography. Conclusions: The findings in our patient suggest that a decline in adrenal androgens after glucocorticoid treatment resulted in an increase in gonadotropin levels and the giant cyst is developed by activation of gonadotropin cascade and increased gonadotropin receptors, instead of androgens.

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.

Congenital adrenal hyperplasia in children

2011 ◽  
pp. 1137-1147
Author(s):  
Felix G. Riepe
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Clinical Picture ◽  
Point Of View ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Comprehensive Overview ◽  
21 Hydroxylase Deficiency ◽  
Paediatric Endocrinologist

Congenital adrenal hyperplasia (CAH) is caused by the genetic impairment of one of the five enzymes required for the biosynthesis of cortisol from cholesterol. In 95% of cases 21-hydroxylase deficiency (21-OHD) is responsible for the disease (1). Classic 21-OHD has an incidence varying from 1:11 800 to 1:21 800, depending on the population background. The pathophysiology, clinical picture, genetics, and the unique aspects of management from the point of view of the paediatric endocrinologist are addressed, and the problems encountered from birth to puberty are described. The child specific issues of rare forms of CAH are summarized thereafter. The reader is referred to Chapter 5.11 for a comprehensive overview of 21-OHD and for more details on all other forms of CAH.

Sign in / Sign up

Export Citation Format

Share Document