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A Particular Phenotype in a Girl with Aldosterone Synthase Deficiency

Department of Medicine and Experimental Oncology, Hypertension Unit, University of Torino (T.A.W., P.M., F.V.), 10133 Torino, Italy; Centro Diagnostico Italiano (M.B.), 20152 Milan, Italy; Department of Endocrinology, University of Sassari (M.P.), 07100 Sassari, Italy; Institute of Pharmacology, University of Heidelberg (S.L.), 69120 Heidelberg, Germany; and Department of Medical and Surgical Sciences-Endocrinology, University of Padova (D.A.), 35128 Padova, Italy

Address all correspondence and requests for reprints to: Dr. Paolo Mulatero, Hypertension Unit, San Vito Hospital, Strada San Vito 34, 10133 Torino, Italy. E-mail: paolo.mulatero{at}libero.it.

Aldosterone synthase deficiency (ASD) usually presents in infancy as a life-threatening electrolyte imbalance. A 4-wk-old child of unrelated parents was examined for failure to thrive and salt-wasting. Notable laboratory findings were hyperkalemia, high plasma renin, and low-normal aldosterone levels. Urinary metabolite ratios of corticosterone/18-hydroxycorticosterone and 18-hydroxycorticosterone/aldosterone were intermediate between ASD type I and type II. Sequence analysis of CYP11B2, the gene encoding aldosterone synthase (P450c11AS), revealed that the patient was a compound heterozygote carrying a previously described mutation located in exon 4 causing a premature stop codon (E255X) and a further, novel mutation in exon 5 that also causes a premature stop codon (Q272X). The patient’s unaffected father was a heterozygous carrier of the E255X mutation, whereas the unaffected mother was a heterozygous carrier of the Q272X mutation. Therefore, the patient’s CYP11B2 encodes two truncated forms of aldosterone synthase predicted to be inactive because they lack critical active site residues as well as the heme-binding site. This case of ASD is of particular interest because despite the apparent lack of aldosterone synthase activity, the patient displays low-normal aldosterone levels, thus raising the question of its source.

T.A.W. and P.M. contributed equally to this work.

Abbreviations: ASD, Aldosterone synthase deficiency; B, corticosterone; DOC, deoxycorticosterone; HML, human mononuclear leukocyte; 18OHB, 18-hydroxycorticosterone.