scholarly journals Simple Virilizing 21-Hydroxylase Deficiency

2020 ◽  
Author(s):  
Keyword(s):  
Hydroxylase Deficiency ◽  
Simple Virilizing ◽  
21 Hydroxylase Deficiency

Therapeutic challenges in a patient with the simple virilizing (SV) form of congenital adrenal hyperplasia (CAH) due to the P30L/I172N genotype

2019 ◽  
Vol 32 (5) ◽  
pp. 543-547 ◽  
Author(s):  
Maja Tankoska ◽  
Violeta Anastasovska ◽  
Marina Krstevska-Konstantinova ◽  
Michel Naydenov ◽  
Mirjana Kocova
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Polymerase Chain Reaction Amplification ◽  
Point Mutations ◽  
External Genitalia ◽  
High Serum ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Her Family ◽  
Simple Virilizing ◽  
21 Hydroxylase Deficiency

Abstract Background Steroid 21-hydroxylase deficiency is an autosomal recessive disorder, present in 90–95% of all cases with congenital adrenal hyperplasia (CAH). The classical simple virilizing (SV) form of the disease causes virilization of the external genitalia in newborn females and pseudo-precocious puberty in both sexes, due to reactive androgen overproduction. Case presentation We describe a 3.5-year-old girl presenting with pubarche, P2 according to Tanner, advanced bone age of 6 years and 10 months, and high serum levels of 17-hydroxyprogesterone (17-OHP). Molecular analysis of the nine most common pseudogene-derived CYP21A2 point mutations was performed in the patient and her family members using the polymerase chain reaction/amplification-created restriction site (PCR/ACRS) method. We detected the P30L/I172N genotype in the patient. She had inherited a mild P30L mutation from her mother and a severe I172N mutation from her father. Conclusions Although the CAH phenotype is determined by the allele that produces most of the enzyme activity and the mild non-classical (NC) phenotype should be expected, the mild P30L known to be more virilizing probably induced the classical SV phenotype in our patient. A continuous regimen of hydrocortisone at a recommended dose failed to decrease the 17-OHP sufficiently. Careful tapering of the dose did not help, and her pubic hair advanced to P3 according to Tanner. Individually tailored treatment is warranted in this patient.

Substitutions in the CYP21A2 promoter explain the simple-virilizing form of 21-hydroxylase deficiency in patients harbouring a P30L mutation

2005 ◽  
Vol 62 (2) ◽  
pp. 132-136 ◽  
Author(s):  
Rogerio S. Araujo ◽  
Ana Elisa C. Billerbeck ◽  
Guiomar Madureira ◽  
Berenice B. Mendonca ◽  
Tania A. S. S. Bachega
Keyword(s):  
Hydroxylase Deficiency ◽  
Simple Virilizing ◽  
21 Hydroxylase Deficiency

scholarly journals Two Adults with Adrenal Myelolipoma and 21-Hydroxylase Deficiency

2009 ◽  
Vol 2009 ◽  
pp. 1-4 ◽  
Author(s):  
Ingrid Nermoen ◽  
Ivar Følling ◽  
Kjetil Vegge ◽  
Arne Larmo ◽  
Bjørn Gunnar Nedrebø ◽  
...  
Keyword(s):  
Benign Tumors ◽  
Compound Heterozygous ◽  
Adult Males ◽  
Acth Stimulation ◽  
Hydroxylase Deficiency ◽  
Adrenal Myelolipoma ◽  
Adrenal Masses ◽  
Simple Virilizing ◽  
The Masses ◽  
21 Hydroxylase Deficiency

We present incidentally discovered adrenal myelolipomas in two adult males with untreated congenital adrenal hyperplasia (CAH). The patients had simple virilizing form of CAH due to mutations in theCYP21gene coding for 21-hydroxylase; one was heterozygous for the I172N mutation and the other compound heterozygous for the I172N and I2splice mutations. The masses were not removed since myelolipomas are considered benign tumors, and the tumor size did not increase during four- and nine-year observation periods. An adrenal myelolipoma is an important exception to the rule that large tumours should be removed. Untreated CAH with prolonged excessive ACTH stimulation might contribute to the growth of adrenal masses. CAH should be considered as a differential diagnosis of patients with adrenal masses or adrenal myelolipomas.

The distribution of intrafamilial CYP21A2 mutant alleles and investigation of clinical features in Turkish children and their siblings in Southeastern Anatolia

2019 ◽  
Vol 32 (12) ◽  
pp. 1311-1320
Author(s):  
Murat Karaoglan
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Consanguineous Marriage ◽  
Adrenal Hyperplasia ◽  
Regional Variability ◽  
Hydroxylase Deficiency ◽  
Turkish Children ◽  
Salt Wasting ◽  
Allele Number ◽  
Simple Virilizing ◽  
21 Hydroxylase Deficiency

Abstract Background The genotype-phenotype relationship shows regional variability in 21-hydroxylase deficiency (21-OHD) caused by mutations in the CYP21A2 gene. This study focuses on the genotype-phenotype compatibility between patients and their siblings in a region where consanguineous marriage is common. Methods The most common mutations (I2G-P30L-I172N-V237E-M239K-V281L-Q318X-R356W-F306 + nt) were studied in 60 children with 21-OHD and 40 siblings (12 symptomatic and 28 asymptomatic; mean age 5.89 ± 4.63 and 8.34 ± 2.22 years, respectively). The allele number (patients; 93 siblings; 70 alleles) was counted for each case. Salt wasting (SW; n = 38), simple virilizing (SV; n = 11) and non-classical congenital adrenal hyperplasia (NCCAH; n = 11) types were compared with their genotypes classified into groups Null-AB-C-D-E based on enzyme impairment. Results Disease-causing mutations were identified in unrelated alleles: 80 out of 93 alleles (86%) in the patients: SW, 51/56 (91%); SV, 14/16 (87.4%) and NCCAH, 15/21 (71.4%). There were 43 out of 70 alleles (61.4%) in the siblings (asymptomatic, 25/50 [50%]; symptomatic, 18/20 [90%]). The most frequently detected mutations in the patients were: I2G (22%), Q318X-P30L-V281L (13% each). The distribution of the most common mutations by clinical types was: SW: I2G-Q318X (30.2%-19.6%), SV: I172NI2G (37.5%-18.7%), NCCAH: V281L-P30L (33.3%-28.5%). In patients and symptomatic siblings, the concordance percentages by genotype groups were: Null (100%-100%), A (85%-60%), B (100%-Not applicable), C (41.6%-50%). Eleven out of 28 asymptomatic siblings had disease-causing mutations (four, severe; one, moderate; six, mild). The distribution of genotypes by phenotypes were: SW: Null-A (88%), SV: B-A (50%-41.6%), NCCAH: C (100%). Conclusions This study showed that the most common alleles were IN2G-Q381X-R356W-P30L-V281L in the children with 21-OHD and asymptomatic siblings, and that the phenotype can be predicted from the genotype except for the P30L-V281L. This result suggests that the most common mutations in 21-OHD are similar to previous reports, but that the genotype-phenotype compatibility is good except for group C showing regional variability, and that genotyping of siblings discovered new patients.

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