scholarly journals A Case Report on Congenital Adrenal Hyperplasia, Varicella Zoster Infection, Varicella Encephalopathy & Cerebellitis

2021 ◽  
Vol 6 (2) ◽  
pp. 308-311
Author(s):  
Aswathy M Shaji ◽  
A. Priya ◽  
S Suwitha
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Neuronal Damage ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Cyp21a2 Gene ◽  
Varicella Zoster ◽  
Adrenal Steroidogenesis ◽  
Increased Risk ◽  
21 Hydroxylase Deficiency ◽  
Varicella Zoster Infection

Congenital adrenal hyperplasia (CAH) comprises a family of autosomal recessive disorder and it will disrupt adrenal steroidogenesis. The most common form of CAH is due to 21-hydroxylase deficiency associated with mutations in the cyp21a2 gene which is located at chromosome 6p21. The clinical features associated with this adrenal steroidogenesis represent a clinical spectrum reflecting to the consequences of the specific mutations. Treatment goals include normal linear growth velocity and “on-time” puberty in affected children. [1] Infection with Varicella zoster virus (vzv) causes chickenpox means Varicella that can be severe in immunocompromised individuals, infants and adults. The primary infection is followed by latency in ganglionic neurons. During this time, no virus particles will produce and no obvious neuronal damage occurs. Reactivation of virus leads to virus replication, which will causes zoster (shingles) in tissues innervated by the involved neurons, inflammation and cell death [2]. Potential complications of this infection are involved in the central nervous system causing encephalitis. An increased risk of this complication is associated with the immunocompromised patient. [3] Keywords: congenital adrenal hyperplasia, varicella zoster infection, varicella encephalopathy, cerebellitis.

Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency: An Update on Genetic Analysis of CYP21A2 Gene

2020 ◽  
Author(s):  
Berta Carvalho ◽  
C.Joana Marques ◽  
Rita Santos-Silva ◽  
Manuel Fontoura ◽  
Davide Carvalho ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Congenital Adrenal Hyperplasia ◽  
Late Onset ◽  
Molecular Genetic Analysis ◽  
Clinical Severity ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Cyp21a2 Gene ◽  
Pathogenic Variants ◽  
21 Hydroxylase Deficiency

AbstractCongenital Adrenal Hyperplasia is a group of genetic autosomal recessive disorders that affects adrenal steroidogenesis in the adrenal cortex. One of the most common defects associated with Congenital Adrenal Hyperplasia is the deficiency of 21-hydroxylase enzyme, responsible for the conversion of 17-hydroxyprogesterone to 11-deoxycortisol and progesterone to deoxycorticosterone. The impairment of cortisol and aldosterone production is directly related to the clinical form of the disease that ranges from classic or severe to non-classic or mild late onset. The deficiency of 21-hydroxylase enzyme results from pathogenic variants on CYP21A2 gene that, in the majority of the cases, compromise enzymatic activity and are strongly correlated with the clinical severity of the disease. Due to the exceptionally high homology and proximity between the gene and the pseudogene, more than 90% of pathogenic variants result from intergenic recombination. Around 75% are deleterious variants transferred from the pseudogene by gene conversion, during mitosis. About 20% are due to unequal crossing over during meiosis and lead to duplications or deletions on CYP21A2 gene. Molecular genetic analysis of CYP21A2 variants is of major importance for confirmation of clinical diagnosis, predicting prognosis and for an appropriate genetic counselling. In this review we will present an update on the genetic analysis of CYP21A2 gene variants in CAH patients performed in our department.

Low Adrenomedullary Function Predicts Acute Illness in Infants with Classical Congenital Adrenal Hyperplasia

2021 ◽  
Author(s):  
Jonathan Weber ◽  
Veeraya K Tanawattanacharoen ◽  
Amy Seagroves ◽  
Mark C Liang ◽  
Christina M Koppin ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Acute Illness ◽  
First Year ◽  
Plasma Epinephrine ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Young Infants ◽  
Increased Risk ◽  
21 Hydroxylase Deficiency ◽  
First Year Of Life

Abstract Context Youth with classical congenital adrenal hyperplasia (CAH) exhibit abnormal adrenomedullary function with decreased epinephrine levels noted in newborns and young infants. Little is known about how this relates to morbidity during the first year of life. Objective To study plasma epinephrine levels in infants with classical CAH and examine the clinical significance of epinephrine deficiency in the first year of life. Design Prospective cohort study. Setting Study participants were recruited from a pediatric tertiary care center. Patients or Other Participants 36 infants with classical CAH due to 21-hydroxylase deficiency and 27 age-matched unaffected controls with congenital hypothyroidism. Main Outcome Measures Plasma epinephrine levels (N=27), CYP21A2 genotype (N=15), and incidence of acute illnesses from birth to 1 year of age (N=28). Results Epinephrine levels in CAH infants independently predicted illness incidence in the first year of life (β=-0.018, R=-0.45, P=0.02) and were negatively correlated with 17-hydroxyprogesterone at diagnosis (R=-0.51, P=0.007). Infants with salt-wasting CAH exhibited lower epinephrine levels as newborns than simple-virilizing infants (P=0.02). CAH patients had lower epinephrine as newborns than controls (P=0.007) and showed decreases in epinephrine from birth to 1 year of age (P=0.04). Null genotype was associated with lower newborn epinephrine and more illness in the first year of life, compared to less severe mutation categories. Conclusions Lower epinephrine levels are associated with increased risk of illness among CAH infants. While not currently part of clinical standard of care, measuring epinephrine levels and assessing genotype may help predict acute illness in the first year of life.

scholarly journals Molecular Analysis of CYP21A2 Gene Mutations among Iraqi Patients with Congenital Adrenal Hyperplasia

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Ruqayah G. Y. Al-Obaidi ◽  
Bassam M. S. Al-Musawi ◽  
Munib Ahmed K. Al-Zubaidi ◽  
Christian Oberkanins ◽  
Stefan Németh ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Molecular Analysis ◽  
Point Mutations ◽  
Gene Mutations ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Cyp21a2 Gene ◽  
Gene Deletions ◽  
Large Gene ◽  
21 Hydroxylase Deficiency

Congenital adrenal hyperplasia is a group of autosomal recessive disorders. The most frequent one is 21-hydroxylase deficiency. Analyzing CYP21A2 gene mutations was so far not reported in Iraq. This work aims to analyze the spectrum and frequency of CYP21A2 mutations among Iraqi CAH patients. Sixty-two children were recruited from the Pediatric Endocrine Consultation Clinic, Children Welfare Teaching Hospital, Baghdad, Iraq, from September 2014 till June 2015. Their ages ranged between one day and 15 years. They presented with salt wasting, simple virilization, or pseudoprecocious puberty. Cytogenetic study was performed for cases with ambiguous genitalia. Molecular analysis of CYP21A2 gene was done using the CAH StripAssay (ViennaLab Diagnostics) for detection of 11 point mutations and >50% of large gene deletions/conversions. Mutations were found in 42 (67.7%) patients; 31 (50%) patients were homozygotes, 9 (14.5%) were heterozygotes, and 2 (3.2%) were compound heterozygotes with 3 mutations, while 20 (32.3%) patients had none of the tested mutations. The most frequently detected mutations were large gene deletions/conversions found in 12 (19.4%) patients, followed by I2Splice and Q318X in 8 (12.9%) patients each, I172N in 5 (8.1%) patients, and V281L in 4 (6.5%) patients. Del 8 bp, P453S, and R483P were each found in one (1.6%) and complex alleles were found in 2 (3.2%). Four point mutations (P30L, Cluster E6, L307 frameshift, and R356W) were not identified in any patient. In conclusion, gene deletions/conversions and 7 point mutations were recorded in varying proportions, the former being the commonest, generally similar to what was reported in regional countries.

scholarly journals Cardiovascular risk, metabolic profile, and body composition in adult males with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

2011 ◽  
Vol 164 (2) ◽  
pp. 285-293 ◽  
Author(s):  
Henrik Falhammar ◽  
Helena Filipsson Nyström ◽  
Anna Wedell ◽  
Marja Thorén
Keyword(s):  
Cardiovascular Risk ◽  
Congenital Adrenal Hyperplasia ◽  
Older Patients ◽  
Liver Function Tests ◽  
Oral Glucose ◽  
Adult Males ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Increased Risk ◽  
21 Hydroxylase Deficiency

ObjectiveLifelong glucocorticoid therapy in patients with congenital adrenal hyperplasia (CAH) or the disease per se may result in increased cardiovascular risk. We therefore investigated cardiovascular and metabolic risk profiles in adult CAH males.Subjects and methodsWe compared CAH males (n=30), 19–67 years old, with age- and sex-matched controls (n=32). Subgroups of different ages (<30 years or older) and CYP21A2 genotypes (null, I2splice, and I172N as the mildest mutation) were studied. Anthropometry, fat and lean mass measured by dual-energy X-ray absorptiometry, lipids, liver function tests, homocysteine, lipoprotein-(a), glucose and insulin during an oral glucose tolerance test (OGTT), urine albumin, adrenal hormones, and 24 h ambulatory blood pressure measurements were studied.ResultsCAH males were shorter. Waist/hip ratio and fat mass were higher in older patients and the I172N group. Heart rate was faster in older patients, the I2splice, and I172N groups. Insulin levels were increased during OGTT in all patients and in the I172N group. γ-glutamyl transpeptidase was increased in older patients and in the I172N group. Testosterone was lower in older patients. Homocysteine was lower in younger patients, which may be cardioprotective. The cardiovascular risk seemed higher with hydrocortisone/cortisone acetate than prednisolone. Urinary epinephrine was lower in all groups of patients except in I172N.ConclusionsIndications of increased risk were found in CAH males ≥30 years old and in the I172N group. In contrast, younger CAH males did not differ from age-matched controls. This is likely to reflect a better management in recent years.

scholarly journals Fertility recovery in patients with non-classical congenital adrenal hyperplasia caused by 21-hydroxylase deficiency

2018 ◽  
Vol 64 (2) ◽  
pp. 79-84
Author(s):  
Elena L. Soboleva ◽  
Natalia S. Osinovskaya ◽  
Natalia N. Tkachenko ◽  
Vladislav S. Baranov ◽  
Marina A. Tarasova
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Fertility Restoration ◽  
Glucocorticoid Therapy ◽  
Total Testosterone ◽  
Adrenal Hyperplasia ◽  
Miscarriage Rate ◽  
Hydroxylase Deficiency ◽  
Cyp21a2 Gene ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency

Background. Very little research has been devoted to the studying fertility problem in nonclassical congenital adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency. It is difficult to draw definitive conclusions regarding the need for glucocorticoid therapy in NCAH women based on limited data. Therefore, evaluating fertility in patients with NCAH and exploring the possibility of correcting its disturbances seemed to us to be a matter of importance. Aims — to evaluate the reproductive function of patients with NCAH and explore potential treatments for this disorder. Materials and methods. The study group included 60 patients with NCAH aged between 18 and 33 years old. NCAH was diagnosed based on early-morning serum 17-hydroxyprogesterone (17-OHP) levels above 30 nmol/l or 17-hydroxyprogesterone levels after ACTH stimulation above 26 nmol/l and/or characterized by molecular analysis of the CYP21A2 gene. Ultrasonography of the uterus and ovaries were performed in the cycle’s follicular phase. Total testosterone, dehydroepiandrosterone sulfate (DHEAS), Androstenedione, 17-OHP and Progesterone was measured. Results. Overall, the patients complained of menstrual cycle disorders (60%), infertility — (28%), hirsutism — (63%). Prior to being diagnosed with NCAH, Thirty-four women sought care because of infertility or recurrent miscarriages. Seventeen women (50%) had miscarriages; later on, five of them developed secondary infertility. Two patients became pregnant without treatment being already diagnosed and progressed to delivery. Once the diagnosis of NCAH was made, 58 women started receiving glucocorticoid therapy, Thirty nine (67%) women became pregnant while on glucocorticoid therapy. Thus glucocorticoid therapy reduced the miscarriage rate from 50 to 10.3%; р<0.001. There was no difference in the miscarriage rate between patients who received or quit glucocorticoid therapy during pregnancy. Conclusions. Glucocorticoid therapy is a highly efficacious method of fertility restoration in NCAH patients. Use of glucocorticoids during pregnancy planning significantly reduced the miscarriage rate. No difference in pregnancy outcome between the patients who received glucocorticoid therapy during pregnancy as opposed to those who did not indicates the advisability of treatment discontinuation once pregnancy is determined.

scholarly journals Genotype-Phenotype Correlation in Patients with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency in Cuba

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Tania Mayvel Espinosa Reyes ◽  
Teresa Collazo Mesa ◽  
Paulina Arasely Lantigua Cruz ◽  
Adriana Agramonte Machado ◽  
Emma Domínguez Alonso ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Point Mutations ◽  
Clinical Manifestations ◽  
Adrenal Hyperplasia ◽  
Phenotype Correlation ◽  
Hydroxylase Deficiency ◽  
Cyp21a2 Gene ◽  
Genotype Phenotype Correlation ◽  
21 Hydroxylase Deficiency ◽  
Cuban Population

Background. There are several studies that show a good genotype-phenotype correlation in congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD). However, there is well-documented evidence of inconsistency in some cases. Objectives. To determine if there is a correlation between the identified mutations and the clinical manifestations of 21OHD in the Cuban population. Methods. A cross-sectional descriptive study of all patients referred for a molecular diagnosis of 21OHD in Cuba from January 2000 to December 2018. The clinical manifestations of each patient were identified and classified according to the phenotype. The CYP21A2 gene was analyzed for the presence of 5 point mutations involved in the pathogenesis of 21OHD (intron 2, deletion of 8bp, I172N, P30L, and Q318X); correlation was sought between the phenotypic characteristics and the frequencies of point mutations in the patients using the Spearman test. Results. A total of 55 patients underwent direct analysis of the CYP21A2 gene in order to determine the presence of the 5 point mutations. Point mutations were identified in 31 patients, which corresponded to 56%. A statistically significant genotype-phenotype correlation was found. Conclusions. The correlation between the detected molecular defect and the clinical expression of 21OHD was reasonable in the Cuban population, which could allow phenotypic predictions to be made from the genotype.

The Spectrum of Genetic Defects in Congenital Adrenal Hyperplasia in the Population of Cyprus: A Retrospective Analysis

2019 ◽  
Vol 51 (09) ◽  
pp. 586-594 ◽  
Author(s):  
Vassos Neocleous ◽  
Pavlos Fanis ◽  
Meropi Toumba ◽  
Charilaos Stylianou ◽  
Michalis Picolos ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Cyp21a2 Gene ◽  
Salt Wasting ◽  
Greek Cypriot ◽  
Frequent Mutations ◽  
Simple Virilizing ◽  
21 Hydroxylase Deficiency ◽  
Greek Cypriots

AbstractCongenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is caused by mutations in the CYP21A2 gene. The study refers to CAH patients of Greek-Cypriot ancestry between years 2007 and 2018. One hundred and twenty patients with various degrees of CAH were categorized and genotyped. The patients were categorized in 4 mutation groups based on their clinical and biochemical findings. The majority of patients (85.0%) belonged to the non-classic (NC)-CAH form and the disorder was more often diagnosed in females (71.7%). The most severe classic salt-wasting (SW) form was identified in 11 neonates (9.2%). Seven (5.8%) children were also identified with the simple virilizing (SV) form and a median presentation age of 5 years [interquartile range (IQR) 3.2–6.5]. In the 240 nonrelated alleles, the most frequent mutation was p.Val281Leu (60.0%) followed by c.655 A/C>G (IVS2–13A/C>G) (8.8%), p.Pro453Ser (5.8%), DelEx1–3 (4.6%), p.Val304Met (4.6%), and p.Gln318stop (4.2%). Other less frequent mutations including rare deletions were also identified. Following our recent report that the true carrier frequency of CYP21A2 in Greek-Cypriots is 1:10, this study reports that the CAH prevalence is predicted around 1.7 cases per 10 000 people. Therefore, the up-to-date 120 CAH patients identified by our group make only the 6.9% of the ones estimated (approximately 1750) to exist in the Greek Cypriot population. The compiled data from a coherent population such as the Greek-Cypriot could be valuable for the antenatal diagnosis, management and genetic counselling of the existing and prospect families with CAH.

Congenital adrenal hyperplasia

2010 ◽  
pp. 1891-1900
Author(s):  
I.A. Hughes
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Ambiguous Genitalia ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Salt Wasting ◽  
Recessive Mutations ◽  
Adrenal Steroidogenesis ◽  
Life Threatening ◽  
Adrenal Rest ◽  
21 Hydroxylase Deficiency

Congenital adrenal hyperplasia (CAH) results from enzymatic defects in the pathways of adrenal steroidogenesis, with over 90% of cases being due to 21-hydroxylase deficiency caused by autosomal recessive mutations in the CYP21 gene. Classical presentation—this is in the neonatal period with ambiguous genitalia/virilization of a female infant, with phenotype traditionally subdivided according to the presence (75%) or absence of salt wasting, which in affected males is the sole manifestation (and can, if unrecognized, be life-threatening). Delayed presentations can occur, manifest in women as hirsutism, oligomenorrhoea, and infertility and in men as infertility or testicular adrenal rest tumours....

scholarly journals Four Novel Missense Mutations in the CYP21A2 Gene Detected in Russian Patients Suffering from the Classical Form of Congenital Adrenal Hyperplasia: Identification, Functional Characterization, and Structural Analysis

2006 ◽  
Vol 91 (12) ◽  
pp. 4976-4980 ◽  
Author(s):  
Yulia Grischuk ◽  
Petr Rubtsov ◽  
Felix G. Riepe ◽  
Joachim Grötzinger ◽  
Svetlana Beljelarskaia ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Enzyme Analysis ◽  
Missense Mutations ◽  
Adrenal Hyperplasia ◽  
Inherited Disorders ◽  
Hydroxylase Deficiency ◽  
Cyp21a2 Gene ◽  
Functional Relationships ◽  
21 Hydroxylase Deficiency

Abstract Context: Congenital adrenal hyperplasia is a group of autosomal recessive inherited disorders of steroidogenesis. The most frequent cause is the deficiency of steroid 21-hydroxylase (CYP21) due to mutations in the CYP21A2 gene. Objective: We analyzed the functional and structural consequences of the four CYP21A2 missense mutations (C169R, G178R, W302R, and R426C) to prove their clinical relevance and study their impact on CYP21 function. Results: Analyzing the mutations in vitro revealed an almost absent or negligible CYP21 activity for the conversion of 17-hydroxyprogesterone to 11-deoxycortisol and progesterone to deoxycorticosterone. Protein translation and intracellular localization were not affected by the mutants, as could be demonstrated by Western blotting and immunofluorescence studies. Analysis of these mutants in a three-dimensional model structure of the CYP21 protein explained the observed in vitro effects because all the mutations severely interfere either directly or indirectly with important structures of the 21-hydroxylase protein. Conclusion: The in vitro expression analysis of residual enzyme function is a complementary method to genotyping and an important tool for improving the understanding of the clinical phenotype of 21-hydroxylase deficiency. This forms the foundation for accurate clinical and genetic counseling and for prenatal diagnosis and treatment. Moreover, this report demonstrates that the combination of in vitro enzyme analysis and molecular modeling can yield novel insights into CYP450 structure-functional relationships.

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