Dehydroepiandrosterone (DHEA) sulfotransferase (SULT2A1) transforms the androgen precursor DHEA to its inactive sulfate ester DHEAS, which prevents DHEA conversion to active androgens. SULT2A1 requires 3′-phosphoadenosine-5′-phosphosulfate (PAPS) for catalytic activity. This article reports compound heterozygous mutations in PAPSS2, the gene encoding human PAPS synthase 2, in a girl with premature pubarche. Thus, PAPSS2 deficiency appears to be a monogenic adrenocortical cause of androgen excess. This article reports compound heterozygous mutations in PAPSS2 the gene encoding human PAPS synthase 2, in a girl with premature pubarche. PAPSS2 deficiency appears to be a monogenic adrenocortical cause of androgen excess. Hyperandrogenic anovulation is a major clinical feature of the polycystic ovary syndrome, 1 , 2 which affects 5 to 15% of women and is associated with an increased incidence of the metabolic syndrome. 3 – 7 It has been suggested that premature pubarche, characterized by the growth of pubic hair in girls younger than 8 years of age, may be an early sign of the polycystic ovary syndrome. 8 , 9 Premature pubarche is most often the manifestation of premature adrenarche, 10 defined by an early increase in the levels of the adrenal androgen precursor DHEA and its sulfate ester, DHEAS, which is the most abundant steroid . . .