Two different patterns of mini-puberty in two 46,XY newborns with 17β-hydroxysteroid dehydrogenase type 3 deficiency
-
Korcan Demir
,
Melek Yıldız
Abstract
We report two newborns with female external genitalia and bilateral inguinal swelling who were diagnosed with 17β-hydroxysteroid dehydrogenase type 3 deficiency, a rare cause of 46,XY disorder of sexual development. The first case had normal clitoral size and vaginal and urethral openings, palpable gonads in the inguinal region, low testosterone, and low levels of basal and GNRH-stimulated gonadotropin. The second case had similar external genitalia, low testosterone but borderline basal and normal stimulated gonadotropin levels. Low testosterone/androstenedione ratios (0.22 and 0.24, respectively; normal, >0.8) after human chorionic gonadotropin stimulation indicated 17β-hydroxysteroid dehydrogenase type 3 deficiency. HSD17B3 sequencing revealed a homozygous novel mutation (c.464A>C, p.H155P) in exon 6 in the first case and homozygous c.239G>A (p.R80Q) in exon 3 in the second.
Acknowledgments
We would like to thank Dr. S. Acar for referring his patient; Dr. F. Özkınay (Department of Medical Genetics, Ege University, Izmir, Turkey) and Dr. S. Ceylaner (İntergen Genetics Center, Ankara, Turkey) for the molecular analyses; and Dr. İ. Erdoğan and Dr. A. Kutlu (Division of Child Psychiatry, Dr. Behçet Uz Children’s Hospital, İzmir, Turkey) for the psychiatric assessment.
References
1. Minu MG, New MI, Ten S, Sultan C, Bhangoo A. The clinical and molecular heterogeneity of 17βHSD-3 enzyme deficiency. Horm Res Pediatr 2010;74:229–40.10.1159/000318004Search in Google Scholar
2. Ahmed SF, Achermann JC, Arlt W, Balen AH, Conway G, Edwards ZL, Elford S, Hughes IA, Izatt L, Krone N, Miles HL, O’Toole S, Perry L, Sanders C, Simmonds M, Wallace AM, Watt A, Willis D. UK guidance on the initial evaluation of an infant or an adolescent with a suspected disorder of sex development. Clin Endocrinol (Oxf) 2011;75:12–26.10.1111/j.1365-2265.2011.04076.xSearch in Google Scholar
3. Erdogan S, Kara C, Uçaktürk A, Aydin M. Etiological classification and clinical assessment of children and adolescents with disorders of sex development. J Clin Res Pediatr Endocrinol 2011;3:77–83.10.4274/jcrpe.v3i2.16Search in Google Scholar
4. Faisal AS, Iqbal A, Hughes IA. The testosterone: androstenedione ratio in male undermasculinization. Clin Endocrinol 2000;53:697–702.10.1046/j.1365-2265.2000.01166.xSearch in Google Scholar
5. Brook CD, Brown RS. Appendix 2: Normal Values. In: Brook CD, Brown RS, editors. Handbook of Clinical Pediatric Endocrinology, 1st ed. Massachusetts: Blackwell Publishing, 2008:250–5.Search in Google Scholar
6. Neely EK, Hintz RL, Wilson DM, Lee PA, Gautier T, Argente J, Stene M. Normal ranges for immunochemiluminometric gonadotropin assays. J Pediatr 1995;127:40–6.10.1016/S0022-3476(95)70254-7Search in Google Scholar
7. Kulle AE, Riepe FG, Melchior D, Hiort O, Holterhus PM. A novel ultrapressure liquid chromatography tandem mass spectrometry method for the simultaneous determination of androstenedione, testosterone, and dihydrotestosterone in pediatric blood samples: age- and sex-specific reference data. J Clin Endocrinol Metab 2010;95:2399–409.10.1210/jc.2009-1670Search in Google Scholar PubMed
8. Aksglaede L, Sørensen K, Boas M, Mouritsen A, Hagen CP, Jensen RB, Petersen JH, Linneberg A, Andersson AM, Main KM, Skakkebæk NE, Juul A. Changes in anti-Müllerian hormone (AMH) throughout the life span: a population-based study of 1027 healthy males from birth (cord blood) to the age of 69 years. J Clin Endocrinol Metab 2010;95:5357–64.10.1210/jc.2010-1207Search in Google Scholar PubMed
9. Bouvattier C, Carel JC, Lecointre C, David A, Sultan C, Bertrand AM, Morel Y, Chaussain JL. Postnatal changes of T, LH, and FSH in 46, XY infants with mutations in the AR gene. J Clin Endocrinol Metab 2002;87:29–32.10.1210/jcem.87.1.7923Search in Google Scholar PubMed
10. Bilbao JR, Loridan L, Audi L, Gonzalo E, Castano L. A novel missense (R80W) mutation in 17-β-hydroxysteroid dehydrogenase type 3 gene associated with male pseudohermaphroditism. Eur J Endocrinol 1998;139:330–3.10.1530/eje.0.1390330Search in Google Scholar PubMed
11. Geissler WM, Davis DL, Wu L, Bradshaw KD, Patel S, Mendonca BB, Elliston KO, Wilson JD, Russell DW, Andersson S. Male pseudohermaphroditism caused by mutations of testicular 17 beta-hydroxysteroid dehydrogenase 3. Nat Genet 1994;7:34–9.10.1038/ng0594-34Search in Google Scholar PubMed
12. Bertelloni S, Balsamo A, Giordani L, Fischetto R, Russo G, Delvecchio M, Gennari M, Nicoletti A, Maggio MC, Concolino D, Cavallo L, Cicognani A, Chiumello G, Hiort O, Baroncelli GI, Faienza MF. 17beta-hydroxysteroid dehydrogenase-3 deficiency: From pregnancy to adolescence. J Endocrinol Invest 2009;32:666–70.10.1007/BF03345738Search in Google Scholar PubMed
13. Gross DJ, Landau H, Kohn G, Farkas A, Elrayyes E, el-Shawwa R, Lasch EE, Rösler A. Male pseudohermaphroditism due to 17β-hydroxysteroid dehydrogenase deficiency: gender reassignment in early infancy. Acta Endocrinol (Copenh) 1986;112:238–46.10.1530/acta.0.1120238Search in Google Scholar PubMed
14. Lee YS, Kirk JM, Stanhope RG, Johnston DI, Harland S, Auchus RJ, Andersson S, Hughes IA. Phenotypic variability in 17β-hydroxysteroid dehydrogenase-3 deficiency and diagnostic pitfalls. Clin Endocrinol (Oxf) 2007;67:20–8.10.1111/j.1365-2265.2007.02829.xSearch in Google Scholar PubMed
15. The Human Gene Mutation Database. Available at: http://www.hgmd.org, Accessed on April 23, 2014.Search in Google Scholar
16. Alikasifoglu A, Hiort O, Gonc N, Demirbilek H, Isik E, Kandemir N. 17beta-hydroxysteroid dehydrogenase type 3 deficiency as a result of a homozygous 7 base pair deletion in 17betaHSD3 gene. J Pediatr Endocrinol Metab 2012;25:561–3.10.1515/jpem-2012-0009Search in Google Scholar PubMed
17. Rosler A. 17 beta-hydroxysteroid dehydrogenase 3 deficiency in the Mediterranean population. Pediatr Endocrinol Rev 2006;3(Suppl 3):455–61.Search in Google Scholar
18. Chuang J, Vallerie A, Breech L, Saal HM, Alam S, Crawford P, Rutter MM. Complexities of gender assignment in 17β-hydroxysteroid dehydrogenase type 3 deficiency: is there a role for early orchiectomy? Int J Pediatr Endocrinol 2013;2013:15.10.1186/1687-9856-2013-15Search in Google Scholar PubMed PubMed Central
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Articles in the same Issue
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Articles in the same Issue
- Frontmatter
- Highlight: Thyroid
- Thyroid disorders revisited
- Genetic analysis of the paired box transcription factor (PAX8) gene in a cohort of Polish patients with primary congenital hypothyroidism and dysgenetic thyroid glands
- Prognostic factors in pediatric differentiated thyroid cancer patients with pulmonary metastases
- Reclassification of cytologically atypical thyroid nodules based on radiologic features in pediatric patients
- Evaluation of inflammatory and oxidative biomarkers in children with well-controlled congenital hypothyroidism
- Investigation of autoimmune diseases accompanying Hashimoto’s thyroiditis in children and adolescents and evaluation of cardiac signs
- Neonatal thyroid storm accompanied with severe anaemia
- Functional characterization of the novel sequence variant p.S304R in the hinge region of TSHR in a congenital hypothyroidism patients and analogy with other formerly known mutations of this gene portion
- Subclinical hypothyroidism as a rare cofactor in chronic kidney disease (CKD) – related anemia
- Cytometric analysis of perforin expression in NK cells, CD8+, and CD4+ lymphocytes in children with autoimmune Hashimoto’s thyroiditis – a preliminary study
- Papillary thyroid cancer and autoimmune polyglandular syndrome
- Review article
- Should radioiodine be the first-line treatment for paediatric Graves’ disease?
- Image in pediatric endrocrinology
- Diffusion-weighted magnetic resonance imaging in a case of severe classic maple syrup urine disease
- Original articles
- Novel mutations of DAX1 (NR0B1) in two Chinese families with X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism
- Rickets and vitamin D deficiency in Alaska native children
- Persistent elevation of fibroblast growth factor 23 concentrations in healthy appropriate-for-gestational-age preterm infants
- Parents’ experiences of having a baby with ambiguous genitalia
- Effect of GnRHa 3.75 mg subcutaneously every 6 weeks on adult height in girls with idiopathic central precocious puberty
- Congenital adrenal hyperplasia in children – a survey on the current practice in the UK
- Randomized clinical trial evaluating metformin versus oral contraceptive pills in the treatment of adolescents with polycystic ovarian syndrome
- Influence of the body weight on the onset and progression of puberty in boys
- Therapy monitoring in congenital adrenal hyperplasia by dried blood samples
- Hyperinsulinemic hypoglycemia: think of hyperinsulinism/hyperammonemia (HI/HA) syndrome caused by mutations in the GLUD1 gene
- Sulfonylurea in the treatment of neonatal diabetes mellitus children with heterogeneous genetic backgrounds
- Monitoring gonadotropin-releasing hormone analogue (GnRHa) treatment in girls with central precocious puberty: a comparison of four methods
- Dietary intake, body composition, and physical activity among young patients with type 1 diabetes mellitus
- Metabolic syndrome in obese children and adolescents in Serbia: prevalence and risk factors
- Progressive osseous heteroplasia, as an isolated entity or overlapping with Albright hereditary osteodystrophy
- Patient reports
- 17α-Hydroylase/17,20-lyase deficiency related to P.Y27*(c.81C>A) mutation in CYP17A1 gene
- A patient developing anaphylaxis and sensitivity to two different GnRH analogues and a review of literature
- Idiopathic short stature due to novel heterozygous mutation of the aggrecan gene
- Triple A syndrome with a novel indel mutation in the AAAS gene and delayed puberty
- Case report: long-term follow-up of a 45,X male with SHOX haploinsufficiency
- Antenatal Bartter syndrome presenting as hyperparathyroidism with hypercalcemia and hypercalciuria: a case report and review
- Successful use of continuous subcutaneous hydrocortisone infusion after bilateral adrenalectomy secondary to bilateral pheochromocytoma
- Donohue syndrome: a new case with a new complication
- Euprolactinemic galactorrhea secondary to domperidone treatment
- 17βHSD-3 enzyme deficiency due to novel mutations in the HSD17B3 gene diagnosed in a neonate
- Two different patterns of mini-puberty in two 46,XY newborns with 17β-hydroxysteroid dehydrogenase type 3 deficiency
- Short communication
- Early onset hearing loss in autosomal recessive hypophosphatemic rickets caused by loss of function mutation in ENPP1
