DOI: http://dx.doi.org/10.18203/2349-3291.ijcp20212892

Impact of estrogen replacement on growth, skeletal maturation, bone density and body composition in a girl with novel aromatase gene mutation

Neha Agarwal, Rishi Shukla, Anurag Bajpai

Abstract


Aromatase deficiency is a rare autosomal recessive disorder characterized by impaired androgen to estrogen conversion. We report a 13.5-year-old girl initially misdiagnosed as simple virilising 21 hydroxylase deficiency who presented with delayed puberty. Work-up showed aromatase deficiency due to novel mutation in the aromatase gene. Estradiol replacement was associated with increased growth, skeletal maturation, bone density and adiposity. Early estrogen treatment in our case may have prevented metabolic complications and ovarian cysts.  


Keywords


Aromatase deficiency, Estrogen, Disorder of sexual development

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References


Saraco N, Nesi-Franca S, Sainz R, Marino R, Marques-Pereira R, La Pastina J, et al. An Intron 9 CYP19 Gene Variant (IVS9+5G>A), Present in an Aromatase-Deficient Girl, Affects Normal Splicing and Is Also Present in Normal Human Steroidogenic Tissues. Horm Res Paediatr. 2015;84:275-82.

Ludwikowski B, Heger S, Datz N, Richter-Unruh A, González R. Aromatase deficiency: rare cause of virilisation. Eur J Pediatr Surg. 2013;23:418-22.

Marino R, Garrido N, Costanzo M, Guercio G, Juanes M, Rocco C, et al. Five new cases of 46, XX aromatase deficiency: clinical follow-up from birth to puberty, a novel mutation, and a founder effect. J Clin Endocrinol Metab. 2015;100:E301-7.

Belgorosky A, Guercio G, Pepe C, Saraco N, Rivarola MA. Genetic and clinical spectrum of aromatase deficiency in infancy, childhood and adolescence. Horm Res Paediatr. 2009;72:321-30.

Alsaleem M, Miller DE, Saadeh L, Majumdar I. Aromatase deficiency: a rare cause of maternal virilisation and ambiguous genitalia in neonates. BMJ Case Rep. 2019;12pii:e231267.

Janner M, Flück CE, Mullis PE. Impact of estrogen replacement throughout childhood on growth, pituitary-gonadal axis and bone in a 46,XX patient with CYP19A1 deficiency. Horm Res Paediatr. 2012;78:261-8.

Groome NP, Illingworth PJ, O'Brien M, Pai R, Rodger FE, Mather JP, et al. Measurement of dimeric inhibin B throughout the human menstrual cycle. J Clin Endocrinol Metab. 1996;81:1401-5.

Fiçicioglu C, Kutlu T, Baglam E, Bakacak Z. Early follicular antimüllerian hormone as an indicator of ovarian reserve. Fertil Steril. 2006;85:592-6.

Maffei L, Murata Y, Rochira V, Tubert G, Aranda C, Vazquez M, et al. Dysmetabolic syndrome in a man with a novel mutation of the aromatase gene: effects of testosterone, alendronate, and estradiol treatment. J Clin Endocrinol Metab. 2004;89:61-70.

Guercio G, Di Palma MI, Pepe C, Saraco NI, Prieto M, Saure C, et al. Metformin, estrogen replacement therapy and gonadotropin inhibition fail to improve insulin sensitivity in a girl with aromatase deficiency. Horm Res Paediatr. 2009;72:370-6.