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

Recently developed analytical procedures for the qualitative and quantitative analysis of human urine for major and minor steroid metabolites are described. Steroid profile samples were obtained by enzymic hydrolysis with beta-glucuronidase and sulfatase. Methoxime-trimethylsilyl ether derivatives of steroid metabolites were prepared; the recommended procedure converts all ketone groups (except the 11-one group) into methoxime groups and all hydroxyl groups into trimethylsily ether groups. These derivatives are thermally stable, readily volatilized, not subject to dehydration or adsorption on gas chromatographic columns, and suitable for both quanlitative and quantitative analytical studies. Thermostable glass open tubular capillary columns, coated with the non-polar phase SE-30, and containing dispersed particles of silanized silicic acid, were used for the gas chromatographic separation. Illustrations of profiles for normal female and male subjects, and patients with a testosterone-secreting ovarian tumor, congenital adrenal insufficiency and a dehydroepiandrosterone-secreting adrenal tumor are included.
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PMID:High-resolution biomedical gas chromatography. Determination of human urinary steroid metabolites using glass open tubular capillary columns. 12

We are reporting a child with congenital panhypopituitarism, in whom deficient fetal steroidogenesis was suspected prenatally because of undetectable estriol levels measured in the maternal triple-marker screen. No fetal abnormalities were detected by ultrasonography. Amniocentesis demonstrated a normal 46,XX karyotype. Measurement of maternal urinary steroids failed to show elevation in the excretion of the major precursor for estriol, 16 alpha-hydroxydehydroepiandrosterone, indicating that the fetus did not have steroid sulfatase deficiency (placental sulfatase deficiency), the most common genetic cause of extremely low estriol. The steroid analysis excluded other rare single gene defects, including aromatase deficiency and 17 alpha-hydroxylase deficiency. We therefore suspected that the cause of low estriol in this fetus was adrenal insufficiency. Postnatal evaluation was consistent with panhypopituitarism, characterized by deficiency of all anterior pituitary hormones. Because this screen is now offered to more than half the pregnant women in the United States, reports of low estriol levels have become increasingly common. Therefore, it is essential that physicians be familiar with the various etiologies, perform the appropriate antenatal evaluation to determine the specific cause, and closely monitor both mother and child ante- and postnatally.
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PMID:Congenital hypopituitarism as a cause of undetectable estriol levels in the maternal triple-marker screen. 1297 Feb 78

Isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) is a rare cause of adrenocortical insufficiency, especially in children, and may be an underestimated cause of neonatal death. Early postnatal diagnosis may prevent hypoglycemic seizures, Addisonian crises, and death. There are also occasional reports of prenatal diagnosis of IAD by findings on the maternal triple-marker screen (TMST), a combined serum analyte test that measures levels of alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol for the detection of Down syndrome and open neural-tube defects. An isolated low estriol level is usually correlated with compromised uteroplacental perfusion and frequently associated with fetal death. A low estriol level in the context of normal fetal sonography and growth, after exclusion of placental sulfatase deficiency and Smith-Lemli-Opitz syndrome, should raise the suspicion of deficient fetal steroidogenesis, which leads to decreased production of adrenal dehydroepiandrosterone sulfate. We describe 2 brothers with adrenal insufficiency resulting from IAD. The parents are first cousins whose first son is healthy. During the pregnancy of the second son, who died at the age of 7 weeks as a result of presumed cardiomyopathy, a low estriol level on the TMST was ignored because of a normal fetal ultrasound. In the third pregnancy, a low level was found again, and the mother was referred to our tertiary center. Ultrasonography revealed no abnormalities, and karyotype was normal. Normal levels of steroid sulfatase activity and 7-dehydrocholesterol ruled out X-linked ichthyosis and Smith-Lemli-Opitz syndrome, respectively. Postnatally, basal and stimulated cortisol and ACTH levels were low. Other pituitary functions were normal, suggesting the diagnosis of IAD. The patient was treated with a stress dose of hydrocortisone on day 2 of life, which was tapered to a maintenance dose. At the time of this writing, he was 7 months old, with normal growth and development. Recently, loss-of-function mutations in the human TPIT gene were detected in autosomal recessive IAD. TPIT is a cell-restricted T-box transcription factor that is important for the terminal differentiation of pituitary corticotrophs. Therefore, we performed molecular analysis of the TPIT gene, which revealed a new mutation (IVS4+1G>A) that affects the first nucleotide of the splice site at the 5' end of the fourth intron. This stop codon probably leads to loss of TPIT function by nonsense-mediated mRNA decay, as it does for other TPIT nonsense mutations. We recommend that pregnant women with an isolated low estriol level of unexplained etiology be referred for additional evaluation by a multidisciplinary team that includes a geneticist and pediatric endocrinologist. Prompt ACTH testing in the first postnatal days will allow for early diagnosis. The immediate institution of glucocorticoid therapy, with proper instructions for stress management, can prevent unnecessary neonatal death secondary to an easily treatable disease.
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PMID:Low estriol levels in the maternal triple-marker screen as a predictor of isolated adrenocorticotropic hormone deficiency caused by a new mutation in the TPIT gene. 1639 Sep 21