ESPE Abstracts (2016) 86 P-P2-82

A Novel Mutation of HSD3beta2 Presenting as Hypospadias with Salt-wasting in a Male Infant

C.R. Buchanana, J. Kalitsia, L. Ghataorea, N.F. Taylora, O. Clifford-Mobleyb, G. Rumsbyb & R.R. Kapoora

aKing’s College Hospital, London, UK; bUCL Hospitals, London, UK

Background: HSD3B2 is a rare cause of autosomal recessive primary adrenal insufficiency, potentially associated with under virilisation of XY males and virilisation of XX females. We present a case of a male infant presenting at term with ambiguous genitalia (DSD) with underlying diagnosis confirmed biochemically and genetically with a novel mutation of HSD3beta2.

Objective: Case report.

Patients and methods: Baby was born as FTND with no risk factors. Newborn examination revealed perineal hypospadias with chordae; stretched penile length 1.6 cm. Gonads impalpable but identified by ultrasound in inguinal canals as normal testis volumes.

Results: Day 2 bloods; Testo 15 nmol/l (androstenedione >35 nmol/l; 17-OHP 40 nmol/l – both raised – results not available for > 2 weeks); LH <0.1, LH <0.1 IU/l). Short Synacthen Test Day 5 (Baby clinically well but plasma Na 134 mmol/l): cortisol basal 110, 30 min 147, 60 min, 109 nmol/l confirmed adrenal insufficiency. Baby discharged home on hydrocortisone 1.25 mg 6-hourly oral.

Progress: Patient readmitted age 5 days in salt-losing crisis: vomiting, dehydrated, Na 108, K 7.1, urea 12 mmol/l. Treated successfully with IV/oral saline, hydrocortisone and fludrocotisone added in standard doses. Patient stable in follow-up. Urine steroid profile from Day 2 identified 3Beta HSD with cortisol metabolites almost undetectable (in context of normal electrolytes at that time) and high 3B-hydroxy-5-ene steroids. DNA analysis has confirmed a novel, nonsense mutation in HSD3B2 gene: g.5554dupT, c.65dupT, p.Leu22Phefs*27 (nomenclature based on HGVS recommendations (

Conclusion: We report a case of DSD male undervirilisation with primary adrenal insufficiency resulting from a novel, nonsense mutation in HSD3 beta 2 gene. Micropenis is an important sign to merit extended investigation in patients with hypospadias.

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