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Colegio de Medicina Interna de México.

2024, Number 2

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Med Int Mex 2024; 40 (2)

Congenital adrenal hyperplasia caused by a mutation (Val-281-Leu) of the enzyme 21-hydroxylase

Hijuelos ERG, Manzano PM, Silva GJ, Sotelo LMT, Galván GA, Pérez GF, Ahumada AM

Language: Spanish
References: 20
Page: 145-151
PDF size: 220.91 Kb.


ABSTRACT

Background: Congenital adrenal hyperplasia is an autosomal recessive disorder caused by a defect in adrenal steroidogenesis. The non-classical variant begins at puberty and is manifested by menstrual irregularities, hirsutism, genital hyperpigmentation, clitoral hypertrophy, accelerated growth, and elevated levels of testosterone and other androgens. Individuals with these non-classical forms of the disease are born with normal-appearing genitalia and begin clinical manifestations with the steroidogenic stimulus characteristic of adolescence.
Clinical case: A 16-year-old female patient seen at the endocrinology clinic for menstrual irregularities and hirsutism, menarche at 13 years of age with menstrual irregularities (oligomenorrhea) and recession of the frontal hairline, breast and pubic hair development grade 4 on the Tanner scale for both features. The diagnosis of lateonset 21-hydroxylase blockade (non-classical form) was established. Initial treatment consisted of metformin and cyproterone, with marked relieve of hyperandrogenism and correction of menstrual irregularities.
Conclusions: Late-onset non-classical congenital adrenal hyperplasia is due to a homozygous point mutation of the CYP21A2 gene, which in turn is due to a coding error at position 281 of the 21-hydroxylase protein, consisting of a substitution of the amino acid valine for leucine and resulting in complete inactivation of both alleles of the enzyme.


REFERENCES

  1. Latorre S, Garzón C, Manosalva G, Merchón S, JacomussiL, Maldonado S. Hiperplasia adrenal congénita por déficitde 21 hidroxilasa: un reto diagnóstico y terapéutico. Repde Medicina y Cirugía 2016; 25 (2):79-88. http://dx.doi.org/10.1016/j.reper.2016.05.001.

  2. Jha S, Turcu AF. Nonclassic Congenital adrenal hyperplasia:what do endocrinologists need to know? Endocrin MetabClin 2021; 50 (1): 151-65. https://doi.org/10.1016/j.ecl.2020.10.008.

  3. Martín M, Nájera N, Garibay N, Malanco LM, Martinez T,et al. New genetic abnormalities in non-21α-hydroxylasedeficiencycongenital adrenal hyperplasia. Sex Dev 2013;7: 289-94. https://doi.org/10.1159/000356948.

  4. Merke MD, Deborah P, Richard JA. Congenital adrenal hyperplasiadue to 21-hydroxylase deficiency. New Engl J Med2020; 383 (13): 1248-61. doi: 10.1056/NEJMra1909786.

  5. Feldman WS. Congenital adrenal hyperplasia. J PediatrAdolesc Gynecol 2017; 30 (5): 520-34. doi:10.1016/j.jpag.2017.04.001.

  6. Iñiguez ED, Ezquieta-Zubicaray B. Cribado neonatal dehiperplasia suprarrenal congénita. Endocrinol DiabetesNutr 2018; 65 (1): 1-4. http://dx.doi.org/10.1016/j.endinu.2017.11.001.

  7. Hicks JJ. Bioquímica. México: McGraw Hill, 2017; 592-93.

  8. Herrera-Gómez A. Hiperplasia suprarrenal congénita:origen de trastornos del desarrollo y diferenciación sexual.Médicas UIS 2015; 28 (1): 125-32.

  9. El-Maouche D, Arlt W, Merke DP. Congenital adrenal hyperplasia.Lancet. 2017; 390 (10108): 2194-10. http://dx.doi.org/10.1016/s0140-6736(17)31431-9.

  10. González EC, Carvajal F, Frómeta A, Arteaga AL, Castells EM,et al. Newborn screening for congenital adrenal hyperplasiain Cuba: six years of experience. Clin Chim Acta 2013; 421:73-8. https://www.sciencedirect.com/science/article/pii/S0009898113000752

  11. Speiser PW, White PC. Congenital adrenal hyperplasia. NEngl J Med 2003; 349 (8): 776-88.

  12. White PC, Speiser PW. Congenital adrenal hyperplasia dueto 21-hydroxylase deficiency. Endocr Rev 2000; 21 (5): 245-91. https://doi.org/10.1210/edrv.21.3.0398.

  13. Liu SY, Lee CT, Tung YC, Chien YH, Hwu WL, Tsai WY. Clinicalcharacteristics of Taiwanese children with congenital adrenalhyperplasia due to 21-hydroxylase deficiency detectedby neonatal screening. J Formos Med Assoc 2018; 117(2): 126-31. https://doi.org/10.1016/j.jfma.2017.03.008.

  14. Castelo-Branco C, Peralta S. Hiperandrogenismo ovárico.Valoración clínica y terapéutica. Clin Invest Gin Obstet2005; 32 (6): 244-56.

  15. Keen-Kim D, Redman JB, Alanes RU, Eachus MM, Wilson RC,New MI, et al. Validation and clinical application of a locusspecificpolymerase chain reaction- and minisequencingbasedassay for congenital adrenal hyperplasia (21-hydroxylasedeficiency). J Mol Diagn 2005; 7 (2): 236-46. https://doi.org/10.1016/S1525-1578(10)60550-8.

  16. Hinojosa-Trejo M, Arguinzoniz-Valenzuela SL, Del AlbaHerrera-Pérez L, Caamal-Parra G, Ibarra-González I, et al.Aspectos relevantes del tamiz neonatal para hiperplasiasuprarrenal congénita. Acta Pediatr Mex 2018; (39): 14-24.

  17. White PC. Analysis of mutations causing steroid 21-hydroxylasedeficiency. NYP WCM 1989;15 (1-2): 239-56. https://doi.org/10.1080/07435808909039099.

  18. Luz GCM. Prevalencia de hiperplasia suprarrenal congénitadetectada por tamiz neonatal metabólico en la UMF N°73.Universidad Veracruzana, 2020.

  19. McCartney CR, Marshall JC. Polycystic ovary syndrome. NEngl J Med 2016; 375 (1): 54-64. http://dx.doi.org/10.1056/nejmcp1514916.

  20. Nieman LK, Merke DP. Diagnosis and treatment of nonclassic(late-onset) congenital adrenal hyperplasia due to 21-hydroxylase deficiency. UpToDate 2019.




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