17βHSD-3 enzyme deficiency due to novel mutations in the HSD17B3 gene diagnosed in a neonate
-
Elif Sagsak
,
Zehra Aycan
Abstract
17-β-Hydroxysteroid dehydrogenase type 3 (17βHSD-3) is present almost exclusively in the testes, and converts androstenedione (A) to testosterone (T). 17βHSD-3 deficiency is rare. The diagnosis can be missed in early childhood as the clinical presentation may be subtle. The most frequent presentation of 17 HSD-3 deficiency is a 46,XY individual with female external genitalia, labial fusion and a blind ending vagina, with or without clitoromegaly. A low testosterone/androstenedion (T/A) ratio is suggestive of 17βHSD-3 deficiency, and such diagnosis can be confirmed with molecular genetic studies. A 12-day newborn was referred to our hospital because of palpable gonads in the labia majora. On physical examination, the baby had female external genitalia and palpable gonads in the labia majora. T/A ratio was 0.26 and the diagnosis was 17βHSD-3 deficiency, which was confirmed by the evidence of compound heterozygousity novel frameshift mutations in exon 9 and 10 of HSD17B3 gene.
References
1. Houk CP, Hughes IA, Ahmed SF, Lee PA. Consensus statement on managment of intersex disorders. J Pediatr Urol 2006;2:148–62.10.1016/j.jpurol.2006.03.004Suche in Google Scholar
2. Andersson S,Russell DW, Wilson JD. 17-β-hydroxysteroid dehydrogenase 3 deficiency. Trends Endocrinol Metab 1996;7:121–6.10.1016/1043-2760(96)00034-3Suche in Google Scholar
3. Geissler WM, Davis DL, Wu L, Bradshaw KD, Patel S, et al. Male pseudohermaphroditism caused by mutations of testicular 17-β-hydroxysteroid dehydrogenase 3. Nat Genet 1994;7:34–9.10.1038/ng0594-34Suche in Google Scholar PubMed
4. Rosler A. 17 beta-hydroxysteroid dehydrogenase3 deficiency in the Mediterranean population. Pediatr Endocrinol Rev 2006;3:455–61.Suche in Google Scholar
5. Lee YS, Kirk JM, Stanhope RG, Johnston DI, Harland S, et al. Phenotypic variability in 17beta-hydroxysteroid dehydrogenase-3 deficiency and diagnostic pitfalls. Clin Endocrinol (Oxf) 2007;67:20–28.10.1111/j.1365-2265.2007.02829.xSuche in Google Scholar PubMed
6. Balducci R, Toscano V, Wright F, Bozzolan F, Di Piero G, et al. Familial male pseudohermaphroditism with gynaecomastia due to 17 betahydroxysteroid dehydrogenase deficiency. A report of 3 cases. Clin Endocrinol (Oxf) 1985;23:439–444.10.1111/j.1365-2265.1985.tb01102.xSuche in Google Scholar PubMed
7. Mains LM, Vakili B, Lacassie Y, Andersson S, Lindqvist A, et al. 17betahydroxysteroid dehydrogenase 3 deficiency in a male pseudohermaphrodite. Fertil Steril 2008;89:228 e213–e227.10.1016/j.fertnstert.2007.02.048Suche in Google Scholar PubMed PubMed Central
8. Rosler A, Silverstein S, Abeliovich D. A (R80Q) mutation in 17 betahydroxysteroid dehydrogenase type 3 gene among Arabs of Israel is associated with pseudohermaphroditism in males and normal asymptomatic females. J Clin Endocrinol Metab 1996;81:1827–1831.Suche in Google Scholar
9. Neyzi O, Günöz H, Furman A, Bundak R, Gökçay G, et al. Weight, height, head circumference and body mass index references for Turkish children. Çocuk Sağlığı ve Hastalıkları Dergisi 2008;51:1–14.Suche in Google Scholar
10. Ayfer Alikasiroglu, Olaf Hiort, Nazli Gonc, Huseyin Demirbilek, Emregul lsik, et al. 17p-Hydroxysteroid dehydrogenase type 3 deficiency as a result of a homozygous 7 base pair deletion in 17βHSD3 gene. J Pedialr Endocr Met 2012;25:561–563.Suche in Google Scholar
11. George MM, New MI, Ten S, Sultan C, Bhangoo A. The clinical and molecular heterogeneity of 17βHSD-3 enzyme deficiency. Horm Res Paediatr 2010;74:229–40.10.1159/000318004Suche in Google Scholar PubMed
12. Bertelloni S, Dati E, Hiort O. Diagnosis of 17 beta-hydroxysteroid dehydrogenase deficiency. Expert Rev Endocrinol Metab 2009;4:53–65.10.1586/17446651.4.1.53Suche in Google Scholar
13. Andersson S, Geissler WM, Wu L, Davis DL, Grumbach MM, et al. Molecular genetics and pathophysiology of 17 beta-hydroxysteroid dehydrogenase 3 deficiency. J Clin Endocrinol Metab 1996;81:130–136.Suche in Google Scholar
14. Mendonca BB, Inacio M, Arnhold IJ, Costa EM, Bloise W, et al. Male pseudohermaphroditism due to 17 beta- hydroxysteroid dehydrogenase 3 deficiency. Diagnosis, psychological evaluation, and management. Medicine(Baltimore) 2000;79:299–309.Suche in Google Scholar
©2015 by De Gruyter
Artikel in diesem Heft
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Artikel in diesem Heft
- 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
