Dehydroepiandrosterone (DHEA) sulfotransferase, known as SULT2A1, converts the androgen precursor DHEA to its inactive sulfate ester, DHEAS, thereby preventing the conversion of DHEA to an active androgen. SULT2A1 requires 3'-phosphoadenosine-5'-phosphosulfate (PAPS) for catalytic activity. We have identified compound heterozygous mutations in the gene encoding human PAPS synthase 2 (PAPSS2) in a girl with premature pubarche, hyperandrogenic anovulation, very low DHEAS levels, and increased androgen levels. In vitro coincubation of human SULT2A1 and wild-type or mutant PAPSS2 proteins confirmed the inactivating nature of the mutations. These observations indicate that PAPSS2 deficiency is a monogenic adrenocortical cause of androgen excess.
Source Information
From the Department of Pediatrics — Metabolic and Endocrine Disorders (C.N., J.A.S., R.S., H.L.C.- G.) and the Department of Chemical Endocrinology (F.C.G.J.S.), Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands; the Centre for Endocrinology, Diabetes, and Metabolism, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom (V.D., J.C.M., F.S., N.K., W.A.); and the Endocrine Sciences Research Group, Manchester Academic Science Centre, University of Manchester, Manchester, United Kingdom (N.A.H.).
Drs. Noordam and Dhir contributed equally to this article.
Address reprint requests to Dr. Arlt at the School of Clinical and Experimental Medicine, University of Birmingham, Institute of Biomedical Research, Rm. 225, Wolfson Dr., Birmingham B15 2TT, United Kingdom, or at w.arlt{at}bham.ac.uk.
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