Nationwide neonatal screening for congenital adrenal hyperplasia in sweden: a 26-year longitudinal prospective population-based study.

Importance: Recent reports have questioned the rationale for neonatal screening for congenital adrenal hyperplasia (CAH) owing to low sensitivity in salt-wasting forms and a high rate of recall (ie, a positive finding resulting in a visit to a pediatrician and a second test) in preterm infants.

Objective: To determine the efficiency of the neonatal screening program for CAH in Sweden over time.

Design, Setting, And Participants: Longitudinal prospective population-based study in Sweden.

Galactosemia screening with low false-positive recall rate: the Swedish experience.

Newborn screening was implemented in the 1960s with screening for phenylketonuria (PKU). In the same decade, it became possible to screen for classical galactosemia, a rare autosomal recessive inherited disorder, which is potentially life threatening if not treated. While newborn screening for PKU has become almost universal, galactosemia is included only in a minority of European newborn screening programs.

Profound biotinidase deficiency: a rare disease among native Swedes.

Biotinidase deficiency is an autosomal recessive metabolic disorder included in many newborn screening programmes. Prior to the introduction of screening for biotinidase deficiency in Sweden in 2002, the disorder was almost unknown, with only one case diagnosed clinically. Biotinidase activity was measured in dried blood spots with a semiquantitative method using biotin-6-amidoquinoline as substrate.

Increased neonatal thyrotropin in Down syndrome.

Aim: Down syndrome (DS) is frequently associated with thyroid dysfunction. The aim of this study was to investigate the blood concentration of thyrotropin (TSH) observed at neonatal screening of infants with DS and its possible association with development of hypothyroidism during childhood.

Methods: TSH levels from neonatal screening of 73 children (34 F) with DS born in 1986-1996 were studied retrospectively and compared with those of controls.

Congenital CMV infection: prevalence in newborns and the impact on hearing deficit.

Congenital cytomegalovirus (CMV) infection is asymptomatic in 90% of infected newborns but approximately 10-20% of these infants are at risk of developing sequelae later, mostly hearing deficit. The aims of the study were to investigate the prevalence of congenital CMV infection in a Swedish population of newborns and investigate the relative risk of hearing deficit in newborns with congenital CMV infection. The dried blood spot (DBS) samples of 6060 newborns in southern Stockholm during 12 months (October 2003-June 2004; August 2004-October 2004) were analysed for CMV DNA by TaqMan based real-time PCR.

Patent ductus venosus does not lead to alimentary galactosaemia in preterm infants.

Unlabelled: The aim of this study was to investigate if an open ductus venosus representing a portal-caval shunt can lead to transient "alimentary galactosaemia" in preterm infants fed human breast milk. Twenty-six preterm infants (28-34 wk of gestational age) with open ductus venosus were included. Capillary blood samples for measurement of galactose and glucose were collected before, 30 and 50 min after a meal with breast milk (range 12-23 mL/kg).

Prevalence of the 985A>G mutation in the medium-chain acyl-CoA dehydrogenase (MCAD) gene in Sweden.

The prevalence of the 985A>G mutation in the medium-chain acyl-CoA dehydrogenase gene was determined in the Swedish population. A heterozygote frequency of 1:127 was observed. Morbidity data indicate that most of the homozygotes with this mutation are not diagnosed and probably remain asymptomatic.

Benefits of neonatal screening for congenital adrenal hyperplasia (21-hydroxylase deficiency) in Sweden.

Objectives: The aim of this study was to evaluate the benefits of neonatal screening for congenital adrenal hyperplasia (CAH).

Methods: All children with CAH born in Sweden from January 1989 to December 1994 were subjected to a systematic follow-up. Clinical symptoms were recorded and laboratory data collected.

Carbohydrate-deficient transferrin in galactosaemia.

Carbohydrate-deficient isoforms of transferrin (CDT) were examined in Guthrie cards from patients with galactosaemia before and during dietary treatment for up to 9 y. In untreated patients the CDT values were elevated due to abnormal asialo- and/or disialotransferrin. During treatment, the CDT levels were normal except on a few temporary occasions.

[The routine sampling procedure for PKU should be changed. Venous puncture is less painful than heel lancing].

All newborns in Sweden are screened for phenylketonuria (PKU), among other things, blood usually being sampled by heel lancing. Because it is unnecessarily painful, however, this form of sampling in newborns has recently been questioned. There is reason to recommend sampling from a dorsal hand vein as the method of choice for PKU screening purposes.

Retrospective diagnostics of congenital cytomegalovirus infection performed by polymerase chain reaction in blood stored on filter paper.

Capillary blood samples from 63 infants collected 3-7 days after birth, and thereafter stored on filter papers for 12-18 y, were tested for the presence of CMV DNA by the polymerase chain reaction (PCR) method. Of 16 infants with proven congenital CMV infection (positive virus isolation test in urine sampled within 1 week of age), 13 (81%) had a positive CMV PCR test and 3 (19%) a negative PCR test. All blood samples from 16 control infants without congenital CMV infection (negative virus isolation test in urine sampled within 1 week of age) were CMV PCR-negative.

Antiepileptic drug treatment during pregnancy and neonatal screening results.

Many antiepileptic drugs induce hepatic metabolic enzymes and thus enhance metabolism of steroid and thyroid hormones. Antiepileptic drugs readily cross the placenta and the foetal liver is metabolically active. We therefore evaluated the neonatal screening results of TSH and 17-hydroxyprogesterone in 34 study children and their matched controls.

Glutathione transferases of classes alpha, mu and pi show selective expression in different regions of rat kidney.

1. Glutathione transferases (GST) are mainly cytosolic and occur in multiple forms, which can be arranged in three distinct, structural classes. The different enzyme forms show distinct substrate specificities with electrophilic and genotoxic substances.

Glutathione transferases in rat hepatoma cells. Effects of ascites cells on the isoenzyme pattern in liver and induction of glutathione transferases in the tumour cells.

Rat hepatoma cells grown intraperitoneally as an ascites tumour were analysed with respect to their contents of cytosolic glutathione transferases. In contrast with normal liver tissue, the hepatoma cells were dominated by the class Pi glutathione transferase 7-7. All the major hepatic enzyme forms were down-regulated to almost undetectable concentrations.

Stereoselectivity and regioselectivity of purified human glutathione transferases pi, alpha-epsilon, and mu with alkene and polycyclic arene oxide substrates.

The stereoselectivities of three biochemically distinct human glutathione transferases, the acidic isoenzyme (pi) purified from placenta and the basic (alpha-epsilon) and the near-neutral (mu) isoenzymes purified from liver, were determined with (+/-)-benzo(a)pyrene-4,5-oxide, pyrene-4,5-oxide, and (+/-)-styrene-7,8-oxide as substrates. Transferase mu was highly selective (greater than 95%) for reaction of glutathione with R-configured oxirane carbon atoms of (+/-)-benzo(a)pyrene-4,5-oxide and pyrene-4,5-oxide, whereas transferase pi was highly stereoselective (greater than 95%) for S-configured epoxide carbon atoms of (+/-)-benzo(a)pyrene-4,5-oxide and pyrene-4,5-oxide. The basic transferases (alpha-epsilon) showed relatively low stereoselectivity with these polycyclic arene oxide substrates; glutathione reaction at R-configured oxirane carbons was preferred, but only by about 2-fold.

Conjugation of styrene oxide by the basic and acidic forms of glutathione transferase in the human fetal liver.

Two forms of glutathione transferase were isolated by means of isoelectric focusing of human fetal liver cytosol preparations. The enzyme activity was measured with 1-chloro-2,4-dinitrobenzene as the electrophilic substrate. One peak focused at pH 9-10 (basic form) and the other at pH 4-5 (acidic form).

Detoxification of styrene oxide by human liver glutathione transferase.

Cytosolic glutathione transferase (GST) was investigated in four human livers. The profile of GST activity was determined by isoelectric focusing using 1-chloro-2,4-dinitrobenzene as the electrophilic substrate. Three livers contained at least one basic and a near-neutral isoenzyme (GST mu).

The trans-stilbene oxide-active glutathione transferase in human mononuclear leucocytes is identical with the hepatic glutathione transferase mu.

A glutathione transferase from human mononuclear leucocytes with high activity towards trans-stilbene oxide (GT-tSBO) was purified. GT-tSBO is expressed in only about 50% of the individuals studied. As judged from activity measurements, immunological studies and the fact that only those individuals who express glutathione transferase mu have high activity towards trans-stilbene oxide, it is concluded that the hepatic transferase mu is identical with the glutathione transferase (GT-tSBO) in mononuclear leucocytes.

Rat glutathione transferase 8-8, an enzyme efficiently detoxifying 4-hydroxyalk-2-enals.

Rat glutathione transferase 8-8 is one of the less abundant cytosolic glutathione transferases, accounting for approx. 1% of the total activity with 1-chloro-2,4-dinitrobenzene in liver. The enzyme is eluted at pH 6.

Two distinct forms of glutathione transferase from human foetal liver. Purification and comparison with isoenzymes isolated from adult liver and placenta.

Isoelectric focusing of a cytosol fraction from human foetal liver revealed the existence of an acidic and a basic isoenzyme of GSH transferase. The acidic and basic forms of GSH transferase were purified in good yield by use of ion-exchange chromatography on DEAE-cellulose followed by affinity chromatography on S-hexyl-GSH coupled to epoxy-activated Sepharose 6B. The content of the acidic and the basic isoenzymes of GSH transferase together was calculated to constitute 1-2% of the soluble proteins in the hepatic cytoplasm.

Differences in stereoselectivity and catalytic efficiency of three human glutathione transferases in the conjugation of glutathione with 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene.

The kinetics of the enzyme-catalyzed conjugation of glutathione with (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha -oxy-7,8,9,10 -tetrahydrobenzo(a)pyrene [(+/-)-anti-BPDE] have been studied with the following human cytosolic glutathione transferases: the basic (alpha-epsilon) and near-neutral (mu) isoenzymes from liver, and the acidic (pi) isoenzyme from placenta. When the BPDE concentration was varied (using 5 mM glutathione) the apparent Vmax values for transferases alpha-epsilon, mu, and pi were 38, 570, and 825 nmol X mg-1 X min-1, respectively, with corresponding apparent Km values of 88, 27, and 54 microM. The apparent Km values for glutathione [using 80 microM (+/-)-anti-BPDE] were 0.

Identification of three classes of cytosolic glutathione transferase common to several mammalian species: correlation between structural data and enzymatic properties.

The major isoenzymes of cytosolic glutathione transferase (EC 2.5.1.

Isoenzymes of glutathione transferase in rat kidney cytosol.

Glutathione transferases from rat kidney cytosol were purified about 40-fold by chromatography on S-hexylglutathione linked to epoxy-activated Sepharose 6B. Further purification by fast protein liquid chromatography with chromatofocusing in the pH interval 10.6-7.