ESPE Abstracts (2014) 82 P-D-2-2-280

A 26-Day-Old Japanese Girl with Aldosterone Synthase Deficiency Caused by a Novel Mutation in the CYP11B2 Gene

Satomi Koyamaa, Tatsuo Tsuboia, Naoto Shimuraa, Akie Nakamurab, Toshihiro Tajimab & Osamu Arisakaa

aDepartment of Pediatrics, Dokkyo Medical University, Tochigi, Japan; bDepartment of Pediatrics, Hokkaido University School of Medicine, Hokkaido, Japan

Background: Aldosterone synthase deficiency (ASD) is a rare autosomal recessive disease, presenting with salt wasting and failure to thrive in early infancy. It is caused by inactivating mutations of the CYP11B2 gene.

Objective and hypotheses: Our objective was to describe a Japanese patient with ASD, who presented with failure to thrive and salt wasting.

Method: We present a case report and investigate molecular analysis of CYP11B2 gene.

Results: A 26-day-old Japanese girl of unrelated parents was examined for poor weight gain, vomiting and dehydration. Her height and weight at birth were 46.0 cm and 2820 g with 39 weeks and 5 days gestation and her weight at 26 days old was 2515 g. She drank formula milk only about 400 ml/day and vomited once or twice a day. Laboratory findings showed hyponatremia (125 mEq/l), hyperkalemia (6.7 mEq/l) and metabolic acidosis (PH 7.306, BE-7.6 mmol/l). After infusion therapy started, her laboratory findings and weight gain had improved. But poor weight gain and hyponatremia appeared again at 38 days old after infusion therapy had stopped. At that time, the level of plasma renin activity (PRA) was 580 ng/ml per hour and aldosterone was 27.1 ng/dl. She had been suspected ASD because the normal level of aldosterone compared with highly elevated level of PRA and she had started taking fludrocortisone 0.075 mg/day and sodium chloride 1.8 g/day. Fludrocortisone replacement therapy effectively normalized growth and sodium balance. Sequence analysis of CYP11B2 gene revealed that she had a heterozygous mutation, a novel p.P108L mutation in exon 2 that was inherited from her father and a previously described p.R181W mutation in exon 3 from her mother. The novel p.P108L mutation was considered to lose the CYP11B2 activity because the result of protein function analysis by using Polyphen-2 was probably damaging.

Conclusion: ASD is an important differential diagnosis of diseases associated with failure to thrive and salt wasting in early infants.

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