SAT-210 - An Unusual Presentation of 3-Beta Hydroxysteroid Dehydrogenase Deficiency

Introduction: Deficiency of 3-beta-hydroxysteroid dehydrogenase 2 (3B-HSD2) is a rare cause of congenital adrenal hyperplasia (CAH), with < 200 reported cases worldwide. It has a heterogenous presentation, including presence or absence of salt-wasting, with virilization of the female infant. We report a case of a female infant with 3B-HSD2 deficiency who presented with severe biochemical abnormalities in the absence of significant virilization.

Case: A 3-day-old, full term female infant was hospitalized for poor oral intake and vomiting. Labs were notable for hypernatremia (Na 149 mmol/L) with normal potassium (4.7 mmol/L). Sodium levels and symptoms normalized with intravenous hydration. The newborn screen resulted during admission, showing elevated 17-OH progesterone (17-OHP) at 5160 ng/dl (reference range (ref) < 3500). On exam she had mild labial enlargement and hyperpigmentation, separate vaginal introitus, and absence of palpable gonads. Daily outpatient electrolyte monitoring was arranged while repeat 17-OHP was pending. She was discharged from the hospital after feeding well with appropriate weight maintenance. This test from day of life (DOL) 6 was significantly elevated at 3,079 ng/dl. Further testing was done on DOL 9; electrolytes were normal. ACTH was significantly elevated at 1590 pg/ml (ref 6-48), with cortisol level undetectable. Adrenal steroid profile by liquid chromatography tandem mass spectrometry after cosyntropin stimulation showed the following: 17-OHP 2859 ng/dl, DHEA >20,000 ng/dl, androstenedione 480 ng/dl, 11-desoxycortisol 2184 ng/dl, and 17-OH-pregnenolone >20,000 ng/dl. Peak cortisol was 7.2 ug/dl. Testosterone was modestly elevated at 84 ng/dl; female newborn range is 20-64, with male newborn range 75-400. Renin activity at 1 month of life was 930 ng/ml/h. Based on these findings, in particular elevation of 17-OH-pregnenolone out of proportion to 17-OHP, she was diagnosed with 3B-HSD2 deficiency; genetic testing showed HSD3B2 homozygosity for sequence variant c.818_819del (p.Lys273Argfs*7). She was started on fludrocortisone, hydrocortisone, and sodium chloride. Family received stress dose teaching. At follow-up 2 weeks later she had increased hyperpigmentation of ears, lips, and labia, but was clinically well with appropriate weight gain.

Discussion: In this case of CAH caused by 3B-HSD2 deficiency, electrolytes were only marginally abnormal and virilization was minimal. In addition, her atypical presentation of hypernatremic dehydration at DOL 3, compared to classic salt-wasting after the first week of life, delayed recognition of her disorder. However, she was found to have profound derangements of adrenal steroidogenesis metabolites. In CAH infants with more rare enzyme deficiencies, the newborn screen—and a high level of clinical suspicion—remain vital to detect these abnormalities prior to adrenal crisis.

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