1/5. Reversible cardiomyopathy caused by an uncommon form of congenital adrenal hyperplasia.A child with 11, beta-hydroxylase deficiency, an unusual variant of congenital adrenal hyperplasia, presented with dilated cardiomyopathy. Congestive heart failure and dilatation of ventricles resolved with hydrocortisone replacement therapy. This case highlights the importance of complete history and physical examination of children with dilated cardiomyopathy.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
2/5. Molecular basis of apparent isolated 17,20-lyase deficiency: compound heterozygous mutations in the C-terminal region (Arg(496)Cys, Gln(461) Stop) actually cause combined 17 alpha-hydroxylase/17,20-lyase deficiency. The molecular defect in a reported case of isolated 17,20-lyase deficiency in a 46XY individual has been elucidated. The patient was found to be a compound heterozygote, carrying two different mutant alleles in the CYP17 gene. One allele contains a point mutation of arginine (CGC) to cysteine (TGC) at amino acid 496 in exon 8. The second allele contains a stop codon (TAG) in place of glutamine (CAG) at position 461 in exon 8 which is located 19 amino acids to the carboxy-terminal side of the P-450(17) alpha heme binding cysteine. COS-1 cells transfected with cDNAs containing one or the other of these mutations showed dramatically reduced 17 alpha-hydroxylase and 17,20-lyase activities relative to cells transfected with the wild type P-450(17) alpha cDNA. While the in vitro data in COS 1 cells can explain the patient's physical phenotype, with female external genitalia, it was somewhat discordant with the clinical expression of isolated 17,20-lyase deficiency with relative preservation of 17 alpha-hydroxylase activity in vivo. In addition to the expression studies of these two examples of mutants in the C-terminal region of cytochrome P-450(17) alpha, a third mutant cDNA construct containing a 4-base duplication at codon 480 previously found in patients with combined 17 alpha-hydroxylase/17,20-lyase deficiency was also expressed in COS-1 cells. This expressed protein was completely inactive with respect to both activities, supporting the biochemical findings in serum and in vitro biochemical data obtained using a testis from the patient. The results from these patients clearly indicate the importance of the C-terminal region of human P-450(17) alpha in its enzymatic activities.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
3/5. Triple-x syndrome accompanied by congenital adrenal hyperplasia: case report.The 47,XXX karyotype is a rare sex chromosome anomaly. This karyotype is usually not associated with a characteristic physical phenotype. In the presented case, a triple-X girl patient associated with 11beta-hydroxylase deficiency is identified. The case was referred to the endocrinology Unit at six days of age because of ambiguous genitalia. The karyotype in this case was 47,XXX, an unexpected finding. Diagnosis of 47,XXX individuals remains difficult because specific clinical criteria used to identify this condition are not available. Congenital adrenal hyperplasia has not been previously reported in patients with triple-X syndrome.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
4/5. Mutation in the human gene for 3 beta-hydroxysteroid dehydrogenase type II leading to male pseudohermaphroditism without salt loss.A 5-year-old XY pseudohermaphrodite was found to have a defect of steroid biosynthesis consistent with a partial deficiency of the enzyme 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD). Circulating concentrations of delta 5 steroids and delta 5 urinary steroid metabolites were elevated and remained elevated after orchidectomy. There was no evidence of salt loss, plasma renin being within normal limits, and no detectable glucocorticoid abnormality. The coding sequences of the genes for 3 beta-HSD types I and II were amplified by PCR and screened for mutations by denaturing gradient gel electrophoresis (DGGE) and manual and automatic dna sequencing. A mutation in the gene for 3 beta-HSD type II was observed at codon 173 (CTA-->CGA), leading in the affected patient to a homozygous substitution in which the leucine at residue 173 was altered to an arginine (L173R). The propositus's 2-year-old XX sister was also homozygous for L173R and showed the biochemical characteristics of partial 3 beta-HSD deficiency without clinical symptoms or signs. The mutation segregated as an autosomal recessive. Three related heterozygous adult females showed evidence of a small over-production of delta 5 steroids and steroid metabolites and a variable reduction in ovarian function. Concentrations of delta 5 steroids and steroid metabolites in the heterozygous father of the propositus were within the normal range. These data are discussed in relation to the endocrine causes of pseudohermaphroditism and hirsutism. Evidence for tight linkage between the genes for 3 beta-HSD types I and II was obtained using a microsatellite polymorphism in the third intron of the gene for 3 beta-HSD type II and synonymous and non-synonymous mutations and polymorphisms in the gene for 3 beta-HSD type I. The latter polymorphisms were located 88 bp apart at the 3' end of the type I coding sequence and could be physically resolved as haplotypes using DGGE. The application of DGGE to the analysis of mutations in members of a multigene family is discussed.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
5/5. prenatal diagnosis of congenital lipoid adrenal hyperplasia.BACKGROUND: There are no published reports of prenatal diagnosis of congenital lipoid adrenal hyperplasia, which is the rarest form of congenital adrenal hyperplasia. CASE: Congenital lipoid adrenal hyperplasia was diagnosed prenatally based on the existence of one affected sibling in the family, the presence of an amniotic fluid cell karyotype of 46,XY, the appearance of normal female genitalia on ultrasonography, relatively low amniotic fluid concentration of 17 alpha-hydroxyprogesterone, low maternal plasma and urinary concentrations of estriol, and a positive response to the dehydroepiandrosterone sulfate loading test. CONCLUSION: Congenital lipoid adrenal hyperplasia can be diagnosed prenatally. Treatment in early infancy can lead to normal mental and physical development.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |