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)

Practical and scientific aspects of prenatal detection of genetic disorders is discussed. The indications for intrauterine detection of familial biochemical and particular chromosomal disorders require assessment of the risks of transabdominal amniocentesis and of the reliability of diagnosis. A high degree of experience in cultivating amniotic fluid cells and in performing diagnostic tests is required. The obstetrician performing the amniocentesis should be responsible for referring the family to a physician who will perform the abortion. A high-risk group for which amniocentesis may be especially important includes families in which 1 parent is a carrier of a chromosomal rearrangement and in which the woman is a known carrier of an X-linked recessive disorder so that sex determination is important. A moderate-risk group includes women who become pregnant after age 40 in which the risk of having a child with a chromosomal aberration is greater than 1%. A low-risk group includes women over 35 and women who have previously borne a child with trisomic Down's syndrome. The experience gained in over 300 patients suggests that transabdominal aminocentesis carries minimal risks to mother and fetus. Analyses of amniotic fluid obtained by amniocentesis have resulted in antenatal diagnoses of Pompe's disease (deficient alpha-1, 4-glucosidase), Tay-Sachs disease (deficient hexosaminidase A), mucopolysaccharidosis (quantitative and qualitative changes in mucopolysaccharides), methylmalonic aciduria (increased methylamlonate), and adrenogenital syndrome (increase 17-ketosteroids and pregnanetriol). There is a lack of consensus on the reliability of several of these diagnoses resulting from the direct analysis of amniotic fluid. Analyses of uncultured amniotic fluid cells have resulted in diagnoses of Pompe's disease (ultrastructural changes) and Tay-Sachs disease. Analyses of cultivated amniotic fluid cells have enabled diagnoses of galactosemia (deficient galactose-1-phosphate uridyl transferase), X-linked uric aciduria (by autoradiography), lysosomal acid phosphatase deficiency, metachromatic leukodystrophy (deficientaryl sulfatase A), mucopolysaccharidosis, cystic fibrosis (metachromatic granules), and Marfan's syndrome (metachromatic granules). Methylmalonic aciduria has been detected in utero by marternal methymalonate excretion. Adrenogenital syndrome has been detected by urinary estriol.
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PMID:Present status of amniocentesis in intrauterine diagnosis of genetic defects. 511 31

Twenty-four women out of 7,875 pregnant women who enrolled in a prenatal screening program showed extremely low levels of unconjugated estriol (< 0.15 MOM). In 19 cases, intrauterine fetal death was reported. In 1 case anencephalus was detected. In the remaining 4 cases apparently normal healthy babies (1 female and 3 males) were born following uneventful pregnancies. Physical examination of the 3 boys at 4-6 weeks revealed mild ichthyosis compatible with the X-linked type. Two of them had a positive family history of X-linked ichthyosis. The examination of the girl did not reveal any significant findings. In both cases in which amniocentesis was performed, low levels of steroid sulfatase and arylsulfatase C were found. The prevalence of X-linked ichthyosis in this study is higher than previously reported, i.e. 1:1,300 males. Our results suggest that the prenatal screening program for neural tube defects and for Down's syndrome is useful for the prenatal detection of X-linked ichthyosis as well. These results are in accordance with two recent reports. The implications regarding genetic counseling are discussed.
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PMID:Very low maternal serum unconjugated estriol and prenatal diagnosis of steroid sulfatase deficiency. 779 18

Previous studies suggested the possibility of accelerated lysosomal degradation of brain gangliosides in Alzheimer's disease (AD). As AD pathology affects both neural and nonneural tissues, the aim of this study was to determine possible changes of glycosphingolipid metabolism in available peripheral cells in AD and Down's syndrome (DS). The activities of several lysosomal enzymes involved in catabolism of gangliosides and sulfatides were measured in leukocytes from subjects with dementia of the Alzheimer type, DS, and age-matched controls, by fluorimetry and spectrophotometry using specific substrates. The results showed a statistically significant increase of beta-galactosidase activity in both dementia of the Alzheimer type and DS leukocytes when compared with age-matched controls (p <.01 and p <.05, respectively; Student's t test). Not significantly increased activities of beta-galactosidase, beta-hexosaminidase, beta-hexosaminidase A, and slightly decreased activity of arylsulfatase A were observed in control leukocytes with aging. Our results indicate that a metabolic dysfunction and the acceleration of at least some lysosomal catabolic pathways are present in AD and DS nonneural cells.
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PMID:Leukocyte lysosomal enzymes in Alzheimer's disease and Down's syndrome. 1177 2

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