Genotype-phenotype correlation in patients with congenital adrenal hyperplasia diagnosed by neonatal screening
Keywords:
Congenital adrenal hyperplasia, Mixed function oxygenases.Abstract
Introduction: congenital adrenal hyperplasia encompasses all inherited disorders of adrenal steroidogenesis cortisol, transmitted by autosomal recessive mutations. The enzyme 21-hydroxylase deficiency is the most frequent form of this disease, constituting 90 to 95% of cases.Objective: To correlate the phenotypic characteristics with genotype in patients suffering from congenital adrenal hyperplasia diagnosed by neonatal screening in Holguin province, Cuba.
Material and method: a retrospective descriptive study was performed in 8 neonates with congenital adrenal hyperplasia per 21-hydroxylase deficiency, diagnosed by screening. They were asked for informed consent to perform physical examination and blood collection for the quantification of 17-hydroxyprogesterone and a molecular study that was performed at the Genetic National Center; mutations (P30L, Intron 2, 8 bp deletion and G318X) were sought.
Results: 62.5% of the patients presented clinical symptoms, the two patients who presented the classic salt loss form, which is the severe neonatal disorder, exhibit various mutations in the pseudogene and the active gene mutation Intron 2, where 50% of mothers were homozygous or heterozygous for these mutations.
Conclusions: the most frequent mutation found was Intron 2. Among the clinical features, macrogenitosomia prevailed and simple virilization. The correlation of phenotype-genotype was accomplished to the most affected.
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1. Kukreti P, Kandpal M, Jiloha RC. Mistaken gender identity in non-classical congenital adrenal hyperplasia. Indian J Psychiatry[Internet]. 2014 Apr; [cited 10 May 2014]; 56(2):182-4. Available from: http://www.indianjpsychiatry.org/article.asp?issn=0019-5545;year=2014;volume=56;issue=2;spage=182;epage=184;aulast=Kukreti
2. Kawano A, Kohno H, Miyako K. A Retrospective Analysis of the Growth Pattern in Patients with Salt-wasting 21-Hydroxylase Deficiency. Clin Pediatr Endocrinol[Internet]. 2014 Apr[cited 11 Jun 2014]; 23(2): 27-34. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4004995/
3. Morikawa S, Nakamura A, Fujikura K, Fukushi M, Hotsubo T, Miyata J, Ishizu K, Tajima T. Results from 28 years of newborn screening for congenital adrenal hyperplasia in sapporo. Clin Pediatr Endocrinol[Internet]. 2014 Apr[cited 10 Jun 2014]; 23(2): 35-43. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4004996/
4. Delvecchio M, Soldano L, Lonero A, Ventura A, Giordano P, Cavallo L et al. Evaluation of impact of steroid replacement treatment on bone health in children with 21-hydroxylase deficiency. Endocrine[Internet]. 2014 Jul 1[cited 3 Jul 2014]; 48(3). Available from: http://link.springer.com/article/10.1007/s12020-014-0332-9/fulltext.html
5. Joshi R, Das D, Tamhankar P, Shaikh S. Phenotypic variability in congenital lipoid adrenal hyperplasia. Indian Pediatr[Internet]. 2014 May[cited 3 Jul 2014]; 51(5): 399-400. Available from: http://www.indianpediatrics.net/may2014/399.pdf
6. Al Hosani H, Salah M, Osman HM, Farag HM, El-Assiouty L, Saade D, et al. Expanding the comprehensive national neonatal screening programme in the United arab emirates from 1995 to 2011. East Mediterr Health J[Internet]. 2014 Feb 11[cited 3 Jul 2014]; 20(1): 17-23. Available from: http://applications.emro.who.int/emhj/v20/01/EMHJ_2014_20_1_17_23.pdf
7. Almeida MQ, Kaupert LC, Brito LP, Lerario AM, Mariani BM, Ribeiro M et al. Increased expression of ACTH (MC2R) and androgen (AR) receptors in giant bilateral myelolipomas from patients with congenital adrenal hyperplasia. BMC Endocr Disord[Internet]. 2014 May 12[citado 3 Jul 2014]; 14: 42. Available from: http://www.biomedcentral.com/1472-6823/14/42#
8. Gidlöf S, Wedell A, Guthenberg C, von Döbeln U, Nordenström A. Nationwide neonatal screening for congenital adrenal hyperplasia in sweden: a 26-year longitudinal prospective population-based study. JAMA Pediatr[Internet]. 2014 Jun 1[cited 3 Jul 2014]; 168(6): 567-74. Available from: http://archpedi.jamanetwork.com/article.aspx?articleid=1854340
9. Yang Y, Zhou XY, Zhou XG. Clinical analysis of 52 cases of 21-hydroxylase-deficient congenital adrenal hyperplasia. Zhongguo Dang Dai Er Ke Za Zhi[Internet]. 2015 Jun[cited 3 Jul 2014]; 17(6): 613-7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26108325
10. Odenwald B, Dörr HG, Bonfig W, Schmidt H, Fingerhut R, Wildner M, et al. Classic Congenital Adrenal Hyperplasia due to 21-Hydroxylase-Deficiency: 13 Years of Neonatal Screening and Follow-up in Bavaria. Klin Padiatr[Internet]. 2015 Jun 19[cited 3 Jul 2014]; 227(05): 278-283. Available from: https://www.thieme-connect.de/products/ejournals/abstract/10.1055/s-0035-1554639
11. Falhammar H, Nordenström A. Nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency: clinical presentation, diagnosis, treatment, and outcome. Endocrine[Internet]. 2015 Sep[cited 3 Jul 2014]; 50(1): 32-50. Available from: http://link.springer.com/article/10.1007%2Fs12020-015-0656-0
12. Turcu AF, Auchus RJ. Adrenal Steroidogenesis and Congenital Adrenal Hyperplasia. Endocrinol Metab Clin North Am[Internet]. 2015 Jun[cited 3 Jul 2014]; 44(2): 275-296. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26038201
13. Larrandaburu M, Matte U, Noble A, Olivera Z, Sanseverino MT, Nacul L, et al. Ethics, genetics and public policies in Uruguay: newborn and infant screening as a paradigm. J Community Genet[Internet]. 2015[cited 3 Jul 2015]; 6: 241. Available from: http://download.springer.com/static/pdf/395/art%253A10.1007%252Fs12687-015-0236-2.pdf?originUrl=http%3A%2F%2Flink.springer.com%2Farticle%2F10.1007%2Fs12687-015-0236-2&token2=exp=1443625247~acl=%2Fstatic%2Fpdf%2F395%2Fart%25253A10.1007%25252Fs12687-015-0236-2.pdf%3ForiginUrl%3Dhttp%253A%252F%252Flink.springer.com%252Farticle%252F10.1007%252Fs12687-015-0236-2*~hmac=3b2e44255b2e040b723497001c249405a4eafc80da8eea4d6226dd954407add1
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