Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A rare form of congenital adrenal hyperplasia (CAH), 11 beta-hydroxylase deficiency, may be misdiagnosed as 21-hydroxylase deficiency, the most common form of CAH, because of similar clinical presentations at times and elevated level of 17-hydroxyprogesterone in both conditions. We report a case of 11 beta-hydroxylase deficiency that was originally misdiagnosed as 21-hydroxylase deficiency. Hypertension and hypokalemia complicated with seizures and arrhythmia developed in this 9-year-old girl after abrupt withdrawal of oral dexamethasone but maintenance of fludrocortisone. Suspicion of 11 beta-hydroxylase deficiency led to DNA mutation analysis, which revealed a novel point mutation (CTG 461 CCG) in the CYP11B1 gene converting leucine to proline. Her condition stabilized rapidly after withdrawal of fludrocortisone and administration of hydrocortisone. Regular measurement of blood pressure should be performed in all patients with CAH and test of serum 11-deoxycortisol or deoxycorticosterone level should be performed in those patients with elevated blood pressure to avoid misdiagnosis of 11 beta-hydroxylase deficiency.
 ...
PMID:Congenital adrenal hyperplasia with 11 beta-hydroxylase deficiency. 1554 55

11beta-Hydroxylase deficiency is a common form of congenital adrenal hyperplasia causing virilization of the female fetus and hypertension. DNA analysis of the gene (CYP11B1) encoding 11beta-hydroxylase has been reported previously to be effective in the prenatal diagnosis of one affected female fetus. In that case, prenatal treatment with dexamethasone resulted in normal female genitalia. We now report five new pregnancies that underwent prenatal diagnosis for 11beta-hydroxylase deficiency. In the first family, the proband is homozygous for a T318M mutation and all fetuses from four subsequent pregnancies are carriers. In a second family, the mother is homozygous for a A331V mutation and was started on dexamethasone, but identification of a homozygous normal fetus led to the discontinuation of treatment. In another family, the fetus was a male homozygous for R384Q and treatment was discontinued. Lastly, a novel G444D mutation in exon 8 was identified and proven to reduce 11beta-hydroxylase activity.
 ...
PMID:Update on the prenatal diagnosis and treatment of congenital adrenal hyperplasia due to 11beta-hydroxylase deficiency. 1575 2

Congenital adrenal hyperplasia due to 11beta-hydroxylase enzyme deficiency is a result of the impairment of 11-deoxycortisol to cortisol conversion. In general, it is responsible for less than 5% of the congenital adrenal hyperplasia cases. The clinical expression of androgen excess in females includes several degrees of genital ambiguity, varying from clitoromegaly to complete virilization. Due to the accumulation of mineralocorticoids, approximately 50% of the patients develop blood hypertension. Mutations in the CYP11B1 gene are responsible for the disease. Biochemical and molecular characteristics of the enzyme and their implications in the clinical presentation of 11beta-hydroxylase deficiency are reviewed here.
 ...
PMID:[11beta-hydroxylase deficiency]. 1576 43

The CYP17 gene, located on chromosome 10q24-q25, encodes the cytochrome P450c17 enzyme. Mutations of this gene cause the 17alpha-hydroxylase/17,20-lyase deficiency, which is a rare, autosomal recessive form of congenital adrenal hyperplasia. Approximately 50 different mutations of the CYP17 gene have been described, of which some mutations have been identified in certain ethnic groups. In this study, we present the clinical history, hormonal findings and mutational analysis of two patients from unrelated families, who were evaluated for hypertension, hypokalemia and sexual infantilism. In the first patient, who was a 37-year-old female, additional studies showed a large myelolipoma in the left adrenal gland, and a smaller tumor in the right adrenal gland. In the second patient, who was a 31-year-old phenotypic female, clinical work-up revealed a 46,XY kariotype, absence of ovaries and presence of testes located in the inner opening of both inguinal canals. Analysis of the CYP17 gene by polymerase chain reaction amplification and direct sequencing demonstrated a novel homozygous mutation of codon 440 from CGC (Arg) to TGC (Cys) in both patients. The effect of this novel mutation on 17alpha-hydroxylase/17,20-lyase activity was assessed by in vitro studies on the mutant and wild-type P450c17 generated by site-directed mutagenesis and transfected in nonsteroidogenic COS-1 cells. These studies showed that the mutant P450c17 protein was produced in transfected COS-1 cells, but it had negligible 17alpha-hydroxylase and 17,20-lyase activities. In addition, three-dimensional computerized modeling of the heme-binding site of the P450c17 enzyme indicated that replacement of Arg by Cys at amino acid position 440 predicts a loss of the catalytic activity of the enzyme, as the mutant enzyme containing Cys440 fails to form a hydrogen bond with the propionate group of heme, which renders the mutant enzyme unable to stabilize the proper position of heme. Based on these findings we conclude that expressing the CYP17 gene with functional analysis, combined with three-dimensional computerized modeling of the heme-binding site of the protein provide feasible tools for molecular characterizing of functional consequences of the novel CYP17 mutation on enzyme function.
 ...
PMID:Novel mutation of the CYP17 gene in two unrelated patients with combined 17alpha-hydroxylase/17,20-lyase deficiency: demonstration of absent enzyme activity by expressing the mutant CYP17 gene and by three-dimensional modeling. 1617 74

Seventeen alpha-hydroxylase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia in which defects in the biosynthesis of cortisol and sex steroid result in mineralocorticoid excess, hypokalemic hypertension and sexual abnormalities such as pseudohermaphroditism in males, and sexual infantilism in females. The disease is inherited in an autosomal recessive pattern, and is caused by mutations in the gene encoding cytochrome P450c17 (CYP17), which is the single polypeptide that mediates both 17alpha-hydroxylase and 17,20-lyase activities. We report the case of a 15-year-old patient with 17OHD who had a female phenotype but male karyotype (46,XY). The diagnosis was made based on classical clinical features, biochemical data and molecular genetic study. Two mutations were identified by polymerase chain reaction amplification and sequencing, including a S106P point mutation in exon 2 and a 9-bp (GACTCTTTC) deletion from nucleotide position 1519 in exon 8 of CYP17. The first of these mutations was found in the father and the second in the mother, and both have been previously reported in Asia. The patient's hypertension and hypokalemia resolved after glucocorticoid replacement and treatment with potassium-sparing diuretics. Sex hormone replacement was prescribed for induction of sexual development and reduction of the final height. Prophylactic gonadectomy was scheduled. In summary, 17OHD should be suspected in patients with hypokalemic hypertension and lack of secondary sexual development so that appropriate therapy can be implemented.
 ...
PMID:Seventeen alpha-hydroxylase deficiency. 1647 41

Primary aldosteronism, congenital adrenal hyperplasia, Cushing's syndrome, glucocorticoid-remediable aldosteronism, and corticotropin-dependent forms of adrenal pathology can cause hypertension by excessive production of adrenocortical hormones. Although traditional biochemical assays continue to be used, genetic testing has simplified the diagnosis of glucocorticoid-remediable aldosteronism. Also new interventional radiologic approaches for the diagnosis and treatment of corticotropin-dependent forms of Cushing's syndrome are available. Medical and surgical approaches, however, still remain viable options for treatment.
 ...
PMID:Adrenocortical hypertension. 1512 76

Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a common autosomal recessive disorder characterized by impaired adrenocortical and adrenomedullary function, and adrenal hyperandrogenism. Compared to normal subjects, patients with classic CAH have increased incidence of obesity and visceral adiposity, hyperinsulinism and insulin resistance, hyperleptinemia, hypertension, and hyperandrogenism. It is likely that the impaired adrenomedullary function and intermittent treatment-related hypercortisolism may account for the above abnormalities, and may predispose these subjects to the development of metabolic syndrome-related endothelial dysfunction and atherosclerotic cardiovascular disease in adulthood. Nonpharmacologic and pharmacologic interventions targeting obesity and/or insulin resistance may offer an improved outcome in terms of cardiovascular morbidity.
 ...
PMID:Metabolic syndrome manifestations in classic congenital adrenal hyperplasia: do they predispose to atherosclerotic cardiovascular disease and secondary polycystic ovary syndrome? 1714 32

Mutations in the CYP17 gene impair steroid biosynthesis in the adrenals and gonads, resulting in 17alpha-hydroxylase/17,20-lyase (P450c17) deficiency, leading to amenorrhea, sexual infantilism, hypokalemia, and hypertension. To date, more than 50 mutations in the CYP17 gene associated with congenital adrenal hyperplasia have been described. In this study, we analyzed a 36-year-old phenotypic female, genotypic male, with P450c17 deficiency to compare with an additional group of 50 Chinese subjects without P450c17 deficiency in Taiwan. DNA sequence analysis of the CYP17 gene was performed. The result showed that the proband had a compound heterozygous mutations in exon 6 (CGC-->TGC) that resulted in the substitution of arginine by cysteine at codon 362, and in exon 7 (CCG-->CGG) that resulted in the substitution of proline by arginine at codon 409. In conclusion, we have identified a compound heterozygous mutation in the CYP17 gene in one patient with congenital adrenal hyperplasia in Taiwan.
 ...
PMID:A compound heterozygous mutation in the CYP17 (17alpha-hydroxylase/17,20-lyase) gene in a Chinese subject with congenital adrenal hyperplasia. 1737 8

The differential diagnosis of hypertension associated with hypokalemia in infancy and adolescence should necessarily include deficiency of the 17alpha-hydroxylase enzyme, a rare form of congenital adrenal hyperplasia (CAH). In addition to hypertension, the classic syndrome caused by this deficiency is characterized by suppressed production of sex hormones and consequently sexual infantilism. Although rare (1% of all forms of CAH), there appears to be a higher incidence of this syndrome in some population groups. This is a case report on two sisters followed up at the Department of Obstetrics and Gynecology, School of Medicine, Universidade Estadual de Campinas (UNICAMP), who were both found to have the 46,XY genotype with homozygosis for W406R, exon 7 of the CYP17 gene (OMIM 202110). The condition was diagnosed only at puberty when hypergonadotropic hypogonadism resulted in sexual infantilism; however, arterial hypertension had been present since infancy and late diagnosis and lack of timely adequate treatment resulted in complications.
 ...
PMID:17-Hydroxyprogesterone deficiency as a cause of sexual infantilism and arterial hypertension: laboratory and molecular diagnosis--a case report. 1745 59

The most common cause of congenital adrenal hyperplasia is 21-hydroxylase deficiency (21OHD). The prevalence of hypertension (HTN) in children with 21OHD is unknown, and HTN has not been reported to be a component of this disorder. As children with 21OHD are at risk of developing obesity, we hypothesized that an elevated body mass index (BMI) would be a predictive factor in the development of HTN. A retrospective chart review of children with 21OHD seen in our pediatric endocrine clinics for the past 21 yr was performed. Ninety-one children with 21OHD were identified (54% female). Of these children, six (6.6%) had HTN, and five (5.6%) had essential HTN, which was defined as HTN of unknown etiology. Elevated body mass index was not a determining factor in the development of HTN. Children with 21OHD do appear to have a higher prevalence of HTN when compared to historical reports of pediatric populations. The coexistence of HTN with a salt-wasting state and mineralocorticoid deficiency in some children with 21OHD is paradoxical and of unclear etiology.
 ...
PMID:Observation of hypertension in children with 21-hydroxylase deficiency: a preliminary report. 1752 39


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>