PubMed Health⌕ Search

Biomedical subjects

H Stibler

Publications and source records attributed to H Stibler.

At least 37 records · Page 2Linked to original sources
PubMed1996

[Jaeken's (CDG) syndrome in two sisters].

Jaeken's syndrome or the carbohydrate-deficient glycoprotein (CDG) syndrome, is a newly recognized metabolic syndrome with poor weight gain in children, and multisystematic abnormalities, mainly due to defective carbohydrate entities in many glycoproteins, leading to neurologic dysfunction. Using the standardized method of phenotype evaluation with computer assistance according to the Munich Dysmorphologic Database, two sisters with CDGs were examined to decide if this metabolic entity contains dysmorphic features characterising dysmorphic syndromes. Diagnosis was based on clinical symptomatology and transferrin isoforms which showed tetrasialotransferrin deficiency and increased disialotransferrin in serum. Dysmorphic studies can be helpful in recognition of this syndrome, now described for the first time in Poland.

Adolescent↗
PubMed1995

Carbohydrate-deficient glycoprotein syndrome--a fourth subtype.

Two infants are described, who, we suggest, represent a fourth subtype of carbohydrate-deficient glycoprotein (CDG) syndrome. Both patients showed microcephaly and severe epilepsy with absent psychomotor development and similar minor dysmorphic features. There were no signs of liver dysfunction. Several glycoproteins in blood, including transferrin, alpha 1-antitrypsin, antithrombin and thyroxine-binding globulin, demonstrated abnormal isoforms suggesting a partial deficiency of mainly one or two sialic acid residues. Both the clinical picture and the glycoprotein abnormalities were different from previously defined types of CDG syndrome.

Congenital Disorders of Glycosylation↗
PubMed1995

Gonadal function and glycoprotein hormones in the carbohydrate-deficient glycoprotein (CDG) syndrome.

Six females and six males with carbohydrate-deficient glycoprotein (CDG) syndrome type I, aged 4 months to 43 years, were examined for gonadal function and electrophoretic isoform patterns of four glycoprotein hormones: FSH, LH, TSH and erythropoietin. The female patients had a hypergonadotrophic hypogonadism from an early age without detectable ovaries in three cases. In the males, testosterone levels tended to be low with normal or slightly raised gonadotrophin values. None of the four glycoprotein hormone showed any signs of carbohydrate deficiency of the same type as in many liver-synthesized circulating glycoproteins. It is concluded that females with CDG syndrome type I have primary ovarian failure, and that the syndrome does not affect the terminal charged carbohydrate portion in gonadotrophins, TSH or erythropoietin. The characteristic carbohydrate deficiency in some circulating glycoproteins is thus not a generalized feature in this disease.

Adolescent↗
PubMed1994

Carbohydrate-deficient glycoprotein syndrome: clinical expression in adults with a new metabolic disease.

A new group of recessively inherited metabolic disorders affecting glycoprotein metabolism has been identified--the carbohydrate-deficient-glycoprotein (CDG) syndromes. Here the course and clinical expression of CDG syndrome type I in 13 patients who have passed the age of 15 years are described. All presented with early onset psychomotor retardation, in most cases combined with slight facial dysmorphic features, some degree of hepatic dysfunction, and in one case, pericardial effusion. About half of the patients had subcutaneous lipodystrophy and comatose or stroke-like episodes during childhood. After the age of 15 the disease was mainly characterised by neurological symptoms consisting of non-progressive ataxia associated with cerebellar hypoplasia, stable mental retardation, variable peripheral neuropathy, and strabismus. One third of the patients had generalised seizures, usually sporadic, and all had retinal pigmentary degeneration. In all cases there was more or less pronounced thoracic deformity and no female had passed puberty. Also, the oldest female showed premature aging. Severe internal organ symptoms, which are common in pediatric patients, were absent. All patients had highly raised serum concentrations of the biochemical marker carbohydrate-deficient transferrin, which can be used to verify the diagnosis. It is concluded that after childhood, CDG syndrome type I is a largely non-progressive disease compatible with a socially functioning but dependent lifestyle.

Adolescent↗
PubMed1994

Linkage of a locus for carbohydrate-deficient glycoprotein syndrome type I (CDG1) to chromosome 16p, and linkage disequilibrium to microsatellite marker D16S406.

Carbohydrate-deficient glycoprotein syndrome type I is a multisystem disease with early severe nervous system involvement. The disease, which is inherited as an autosomal recessive trait, is biochemically characterized by complex defects in the terminal carbohydrate residues of a number of serum glycoproteins. This can be most readily detected in transferrin. A whole genome scan was initiated in order to localize the gene (CDG1) with linkage techniques. We analyzed individuals from 25 CDG1 pedigrees with several highly polymorphic microsatellite markers and after exclusion of about 30% of the genome linkage was detected with markers located in chromosome region 16p. The lod score (Zmax) was above 8 (theta max = 0.00) for several markers in this region. In order to further localize the CDG1 gene, recombination and linkage disequilibrium analyses were performed. Recombination events in some pedigrees indicated that the CDG1 gene is located in a 13 cM interval between microsatellite markers D16S406 and D16S500. Furthermore, allelic association was shown for marker D16S406 indicating that the CDG1 gene is located close to this. No heterogeneity could be detected in the European family material tested by us. The positions of cytogenetically localized flanking markers suggest that the location of the CDG1 gene is in chromosome region 16p13.3-p13.12.

Alleles↗
PubMed1994

Detection of relapses in alcohol dependent patients using serum carbohydrate deficient transferrin: improvement with individualized reference levels.

Alcohol dependent male outpatients were monitored for a period of six months. Indicators of alcohol consumption were compared using clinical information three times per week, serum levels of carbohydrate deficient transferrin (CDT) weekly and urine samples of 5-hydroxytryptophol daily. Individualized reference values of CDT were calculated by using an increase of three times the lowest coefficient of variation in the group, which meant that an increase of < or = 30% from the lowest value of each individual was considered a significant increase, and therefore an indication of alcohol consumption. By this approach, it was possible to improve the ability to detect relapses in alcohol dependent patients using serum CDT once a week compared to CDT using reference values recommended by the manufacturer.

Alcohol Drinking↗
PubMed1993

Early manifestations of the carbohydrate-deficient glycoprotein syndrome.

We diagnosed the carbohydrate-deficient glycoprotein syndrome in five children who were seen during their first year of life with failure to thrive, feeding difficulties, psychomotor retardation, hypotonia, esotropia, inverted nipples, lipodystrophy, pericardial effusion, and hepatic dysfunction. Steatosis was observed in liver biopsy specimens, and cerebellar hypoplasia was present on computed tomography. The disorder is characterized by a complex carbohydrate deficiency in certain glycoproteins, notably transferrin, which can be used as a marker of the disease. The carbohydrate-deficient glycoprotein syndrome may be an important and easily identifiable cause of failure to thrive and neurologic dysfunction in infancy. The presence of the disorder in siblings of different gender and the finding of biochemical abnormalities in some unaffected parents suggest an autosomal recessive inheritance.

Biomarkers↗
PubMed1993

Improved electrophoretic method for the analysis of dystrophin in human muscle.

A new simplified electrophoretic and Western blotting technique for the study of dystrophin in muscle biopsy material is presented and compared with immune histochemistry. The method is based on separation of dystrophin in a linear SDS-PAGE pore gradient of 4-8% acrylamide in ultra-thin, horizontal gels on plastic film support followed by horizontal electrotransfer for Western blotting. The advantages of this procedure are short separation and transfer times at high field strength, high resolution, short staining procedures and small requirements of chemicals. Samples from the same gel can be cut and examined with different antibodies. Final results are obtained in one day. Examination of patients with various types of muscular dystrophies verified the essential absence of dystrophin in DMD patients, and showed considerable dystrophin heterogeneity in patients with BMD. A girl with severe symptoms of dystrophy revealed unexpected dystrophin abnormalities. The results also indicated that SDS-PAGE with Western blotting and immune histochemistry are complementary, diagnostic, and research instruments, and that the reactivity of commercial antibodies may differ in these two techniques.

Adult↗
PubMed1993

The carbohydrate-deficient glycoprotein syndromes: pre-Golgi and Golgi disorders?

The carbohydrate-deficient glycoprotein syndromes are a recently delineated group of genetic, multisystemic diseases with major nervous system involvement. Three distinct variants have been recognized and there are probably many more. They are characterized by a deficiency of the carbohydrate moiety of secretory glycoproteins, lysosomal enzymes and probably also membranous glycoproteins. The biochemical changes are most readily observed in serum transferrin and the diagnosis is usually made by isoelectric focusing of this glycoprotein. The deficiency of sialic acid, in particular, results in a cathodal shift and hence the presence of abnormal isoforms of transferrin with higher isoelectric points than normal. The basic defects are probably in the processing and synthesis of the carbohydrate moiety of glycoproteins; there is indirect evidence for a deficiency of asparagine-N-linked oligosaccharide transfer in type I (endoplasmic reticulum defect) and for a deficiency of N-acetylglucosaminyltransferase II in type II (Golgi defect). From the large number of patients detected in only a few years, it is expected that these diseases will become as important as, for example, the lysosomal, peroxisomal or mitochondrial disorders. Their study will undoubtedly yield a wealth of new information on the function of glycoproteins and of their carbohydrate moiety.

Carbohydrate Metabolism, Inborn Errors↗
PubMed1993

Detection of relapses in alcohol-dependent patients: comparison of carbohydrate-deficient transferrin in serum, 5-hydroxytryptophol in urine, and self-reports.

In this study, detection of relapses in male alcohol-dependent patients by biochemical markers and self-reports of alcohol consumption were examined. The patients were trying to stay abstinent from alcohol for 6 months. Four of 15 patients dropped out from treatment after 50-110 days. Ratios of urinary 5-hydroxytryptophol (5-HTOL)/5-hydroxyindole-3-acetic acid and 5-HTOL/creatinine were measured daily and serum carbohydrate-deficient transferrin (CDT) once a week. Clinical ratings and self-reports about alcohol consumption were performed three times a week. According to the self-reports, 3 of the patients drank alcohol frequently, 5 of them sporadically, and 7 of the patients reported no alcohol intake at all. According to the 5-HTOL marker, 4 of the patients drank alcohol frequently, and 11 of them sporadically. No one had all urinary levels of 5-HTOL marker below the reference level. According to the CDT, 3 of the patients drank alcohol frequently, 3 sporadically, and in 9 of the patients no elevated levels of CDT were found. Elevated levels of CDT were preceded by increased values of 5-HTOL marker. The combined results suggested that no one of the patients was totally abstinent from alcohol during the treatment period. The 5-HTOL marker seemed to be useful to reveal recent alcohol drinking, and CDT proved to be useful to validate the patients' self-reports. Together the two biochemical markers showed complementary properties in early detection of relapse and treatment monitoring.

Adult↗
PubMed1993

Diagnosis of alcohol-related neurological diseases by analysis of carbohydrate-deficient transferrin in serum.

Analysis of carbohydrate-deficient transferrin (CDT) in serum has been shown to be a good marker of current regular alcohol consumption at levels that are potentially harmful both to the liver and the nervous system. In this study CDT was analyzed by anion exchange chromatography and the results were evaluated in 134 consecutively examined patients with neurological symptoms of possible or probable alcohol-related etiology. A total of 22% of the patients were regarded as current alcohol abusers and 93% of them had elevated CDT values. The majority of these cases suffered from diseases such as epilepsy, neuropathies, cerebral atrophy/dementia and cerebellopathy. Most of them were still in a socially functioning condition. Low alcohol consuming patients and abstaining patients with a previous history of alcohol abuse had CDT levels within the normal range. The results demonstrated that determination of CDT is a valuable tool in the diagnosis of alcohol-related neurological disorders provided that its biological turnover is taken into account.

Adult↗
PubMed1993

Diagnosis of the carbohydrate-deficient glycoprotein syndrome by analysis of transferrin in filter paper blood spots.

Carbohydrate-deficient glycoprotein syndrome is a recently identified recessively inherited, multisystemic disease with severe nervous system involvement. It is characterized biochemically by carbohydrate-deficient serum glycoproteins, and can be diagnosed by analysis of abnormal isoforms of serum transferrin. Using stored, neonatally collected filter paper blood spots from such patients, it was shown that neonatal diagnosis was possible by immune-isoelectric focusing of transferrin eluted from up to 14-year-old samples. Freshly collected blood on filter paper was readily analyzed quantitatively for carbohydrate-deficient isotransferrins by a rapid microchromatographic assay, revealing highly elevated values in all patients. The presently described methods thus provide a means for early diagnosis of the carbohydrate-deficient glycoprotein syndrome in microliter volumes of capillary blood. Sampling on filter paper offers an important simplification in sample collection, storage and transport, and may make population studies possible.

Blood Specimen Collection↗
PubMed1992

Serum transferrin in patients with retinitis pigmentosa.

The CDG syndrome is a newly detected disorder with a carbohydrate defect in glycoproteins such as transferrin. As retinitis pigmentosa is a part of this syndrome, there could also be other subtypes of retinitis pigmentosa with a similar biochemical defect. Isoforms of serum transferrin were therefore analysed in 78 patients from different families with retinitis pigmentosa and showed slightly or moderately elevated values for less glycosylated isoforms in two families. The study suggests that abnormal glycoprotein metabolism manifested by elevated values of carbohydrate-deficient isotransferrins may be present in a small proportion of families with retinitis pigmentosa. The relationship between the glycoprotein defect and retinitis pigmentosa remains to be established.

Adult↗
PubMed1991

Biophysical and biochemical alterations in erythrocyte membranes from chronic alcoholics.

Erythrocyte membranes from healthy controls and alcoholic patients, examined within 24 h of abstinence, were studied for basal membrane fluidity and membrane sensitivity to ethanol by fluorescence polarization of the apolar probe 1,6-diphenyl-1, 3,5-hexatriene (DPH) and its cationic derivative 1,4(trimethylammonium phenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH). The membrane partition (Kp) of ethanol and phenobarbital, and the concentrations of membrane-bound sialic acid and galactose, were also determined. The apolar hydrocarbon region of the membrane (DPH) was less fluid, in the alcoholics than in the controls (p less than 0.005). In the patients this membrane layer, as well as the polar lipid head group region (TMA-DPH), showed reduced fluidizing effect of ethanol (p less than 0.01). This resistance or tolerance to ethanol correlated with a markedly impaired (-59%, p less than 0.025) partition of ethanol into the membrane. The low Kp of ethanol in turn was partly related to reduced concentrations of polar carbohydrates such as sialic acid and galactose (p less than 0.01) at the membrane surface. The Kp of phenobarbital was reduced in the patients (-59%, p less than 0.005) but, apparently unrelated to the carbohydrate changes. These results indicate that in man, chronic alcohol abuse is associated with complex changes of membrane properties at different membrane levels e.g. at the charged surface, in the polar lipid head group region and in the hydrocarbon core. A partial basis for biophysical membrane tolerance to ethanol is suggested, implying that apart from phospholipid alterations, structural changes in membrane-bound glycoconjugates participate in this adaptive process.

Adult↗