Inactivating PAPSS2 Mutations in a Patient with Premature Pubarche

C Noordam, Vivek Dhir, Joanne McNelis, F Schlereth, NA Hanley, Nils Krone, JA Smeitink, R Smeets, FCGJ Sweep, HL Claahsen-van der Grinten, Wiebke Arlt

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    104 Citations (Scopus)


    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.
    Original languageEnglish
    Pages (from-to)2310-2318
    Number of pages9
    JournalNew England Journal of Medicine
    Issue number22
    Publication statusPublished - 1 May 2009


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