Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.6.1 (sulfatase)
 3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extensive hormonal evaluation was performed in a girl with adrenal carcinoma during the primary tumor stage, following adrenalectomy, during the period when metastases were evident and while on treatment with o,p'-DDD. At the age of 14 months a diagnosis of congenital adrenal hyperplasia was made and treatment with dexamethasone (0.125 to 0.25 mg/day) resulted in a fall-off in growth rate, normal advancement in bone age, decrease in virilization and suppression of 17- ketosteroid excretion which continued until 4 3/12 years of age when virilization increased. At five years of age elevated serum and urinary androgen levels unsuppressible with dexamethasone were noted. Following removal of a large right adrenal carcinoma, serum and urinary hormone levels returned to normal. There months following surgery, liver metastases were documented associated with elevated levels of serum androgens. With o,p'-DDD treatment, serum dehydroepiandrosterone sulfate (DS) and urinary 17-ketosteroid (17-KS) excretion fell rapidly while there was a delay in the fall of free androgens. The persistence of free steroid secretion with decreased formation of DS suggests that the o,p'-DDD may have altered sulfatase activity before causing tumor necrosis and total decrease in steroidogenesis.
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PMID:Virilizing adrenal tumor in a child suppressed with dexamethasone for three years. Effect of o,p'-DDD on serum and urinary androgens. 13 87

Introduction: An increase of serum dehydroepiandrosterone (DHEA) sulfate (DHEAS) is observed in premature adrenarche and congenital adrenal hyperplasia. Very high DHEAS levels are typical for adrenal tumors. Approximately 74% of DHEAS is hydrolyzed to DHEA by the steroid sulfatase (STS). The reverse reaction is DHEA sulfation. Besides these two enzyme reactions, the DHEAS transported through the cell membrane is important for its distribution and excretion. Case Presentation: We present a female adolescent with overweight and a very high DHEAS. The presence of a DHEAS-producing tumor was rejected using ultrasonography, Magnetic Resonance Tomography (MRT), and dexamethasone suppression. STS deficiency was suspected. Sequence analysis revealed a heterozygous nonsense mutation which predicts a truncation of the carboxyl region of the STS that is implicated in substrate binding. No partial gene deletion outside exon 5 was detected by multiplex ligation-dependent probe amplification. The bioassay revealed normal enzyme activity in the patient's leukocytes. A defect of transporter proteins was suggested. Both efflux [multidrug-resistance protein (MRP)2 and breast cancer-resistance protein (BCRP)] and uptake [organic anion-transporting polypeptide (OATP) and organic anion transporter (OAT) carriers] transporters were studied. Sequence analysis of exons revealed a heterozygous Q141K variant for BCRP. Conclusions: A novel heterozygous nonsense mutation in the STS gene and a known heterozygous missense variant in the BCRP gene were found. The heterozygous nonsense mutation in the STS gene is not supposed to be responsible for STS deficiency. The BCRP variant is associated with reduced efflux transport activity only in its homozygous state. The combination of the two heterozygous mutations could possibly explain the observed high levels of DHEAS and other sulfated steroids.
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PMID:Very High Dehydroepiandrosterone Sulfate (DHEAS) in Serum of an Overweight Female Adolescent Without a Tumor. 3243 30