84 results on '"Molzer, B."'
Search Results
2. Abstracts Second Congress of the European Society for Clinical Neuropharmacology: Würzburg, November 9–11, 1995
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Agid, Y., Arendt, T., Gärtner, U., Holzer, M., Fruth, P., Brückner, M. K., Arzberger, T., Weindl, A., Baas, H., Demisch, L., Harder, S., Bürklin, F., Fischer, P. A., Bagli, M., Rao, M. L., Sobanski, T., Laux, G., Barbier, P., Fumagalli, F., Donati, E., Maggio, R., Racagni, G., Corsini, G. U., Riva, M., Berger, J., Löschl, B., Bernheimer, H., Lugowska, A., Tylki-Szymanska, A., Gieselmann, V., Molzer, B., Faé, I., Bernocchi, G., Scherini, E., Necchi, D., Bigl, M., Bleyl, D., Bigl, V., Eschrich, K., Block, F., Schwarz, M., Blum-Degen, D., Müller, Th., Kuhn, W., Gerlach, M., Przuntek, H., Riederer, R., Bonuccelli, U., Ceravolo, R., Nuti, A., D'Avino, C., Placidi, G., Perugi, G., Cassano, G. B., Del Dotto, P., Piccini, P., Colzi, A., Muratorio, A., Braak, H., Braak, E., Yilmazer, D. M., de Vos, R. A. I., Jansen, E. N. H., Bringmann, G., Clement, H. W., Grote, C., Rausch, F., Reichmann, H., Riederer, P., Sontag, K. -H., Wesemann, W., God, R., Feineis, D., Brückner, R., Protzen, J. -A., Fähr, S., Rausch, W. -D., Brunt, E. R. P., Pruim, J., Willemsen, A. J., van Weerden, T. W., Bryan-Lluka, L. J., Bönisch, H., Büttner, Th., Kühn, W., McMonagle, U., Calza, L., Pozza, M., Coraddu, F., Farci, G., Carlsson, A., Napolitano, A., Salvetti, S., Dell'Agnello, G., Renna, M., Conquet, F., Bashir, Z., Daniel, H., Ferraguti, F., Collingridge, G., Crépel, F., Coos Verhoef, J., Merkus, F. W. H. M., Junginger, H. E., Cruz-Sánchez, F. F., Kutschka, T., Beeg, M., Deuschle, M., Weber, B., Körner, A., Standhardt, H., Lammers, C. -H., Motzek-Noé, T., Heuser, I., Earl, C. D., Reum, T., Sautter, J., Xie, J. -X, Kupsch, A., Oertel, W. H., Morgenstern, R., Emilien, G. M., Maloteaux, J. M., Seghers, A., Charles, G., Erdmann, R., Högemann, D., Fichter, N., Lücking, C. H., Landwehrmeyer, G. B., Winter, T., Feuerstein, T. J., Fitzgeral, D., Anderson, M. C., Lawlor, B., Tipton, K. F., Frackowiak, R. S. J., Freo, U., Dam, M., Pizzolato, G., Merico, A., Ori, C., Sale, E., Battistin, L., Fritze, J., Froelich, L., Goetz, M., Gsell, W., Jellinger, K., Beckmann, H., Fünfgeld, E. W., Glinka, Y., Youdim, M. B. H., Götz, M. E., Breithaupt, W., Burger, R., Streifler, M., Simanyi, M., Müller, F., Danielczyk, W., Hirning, T., Sohlbach, M., Nafc, R., Sternadl, H., Winter, M., Nöth, U., Heim, C., Hartmann, J., Künig, G., Niedermeyer, B., Berger, W., Deckert, J., Abel, F., Heinsen, H., Senitz, D., Mayr, J., Ransmayr, G., Hartung, H. -P., Heils, A., Teufel, A., Petri, S., Seemann, M., Bengel, D., Degen, H. J., Lesch, K. P., Sontag, T., Heinen, F., Korinthenberg, R., Heiss, W. -D., Rüb, U., Gangus, B., Jungkunz, G., Bauer, M., Ulmar, G., Böcker, F., Schüler, M., Bethke, B., Lockemann, U., Hermans, E., Vanhoorde, P., Hesse, S., Hüll, M., Fiebich, B., Lieb, K., Strauss, S., Berger, M., Volk, B., Bauer, J., Iversen, L. L., Janetzky, B., Hauck, S., Jeanjean, A. P., Laterre, E. C., Bancher, C., Jost, W. H., Kalus, P., Kanner, B., Khrapova, E. V., Brusov, O. S., Knauber, J., Müller, W. E., Korczyn, A. D., Kornhuber, J., Parsons, C. G., Hartmann, S., Retz, W., Kamolz, S., Thome, J., Koutsilieri, E., Chen, T. -S., Kreutzberg, G. W., Krieglstein, J., Winkel, R., Danielcyk, S., Gerstner, A., Mattern, C., Häcker, R., Labunsky, D., Zhirnova, I., Komelkova, L., Popova, L., Avdiunina, I., Lakke, J. P. W. F., Lange, K. W., Steup, A., Tucha, O., Naumann, M., Lassmann, H., Leszek, J., Gasiorowski, K., Inglot, D., Lohse, M. J., Löschmann, P. -A., Eblen, F., Wüllner, U., Klockgether, T., Dichgans, J., Macrae, I. M., Mimmack, M. L., Emson, P., Norta, M., Borchert, H. -H., Medori, R., Chan, W. W., Heinemann, T., Melzacka, M., Kolasiewicz, W., Sieklucka, M., Jaros, T., Mesec, A., Šega, S., Kiauta, T., Moser, A., Vieregge, P., Siebecker, F., Münch, G., Schinzel, R., Michaelis, J., Cunningham, A., Da Prada, M., Borroni, E., Zürcher, G., Reiners, K., Neveu, P. J., Nitsch, R. M., Pavese, N., Lucetti, C., Rossi, G., Offen, D., Ziv, I., Stein, R., Barzilai, A., Hochman, A., Melamed, E., Ozawa, H., Hashimoto, E., Saito, T., Ymamoto, M., Takahata, N., Frölich, L., Paulus, W., Hermsteiner, E., Haug, B., Bandelow, B., Peckys, D., Gleichauf, O., Jackisch, R., Landwehrmeyer, B., Bloß, H. G., Plaschke, K., Müller, D., Hoyer, S., Avdyuna, L. A., Putzke, J., Spanagel, R., Tolle, T. R., Zieglgänsberger, W., Rabey, J. -M., Orlov, E., von Raison, F., Lehmann, K., Havemann-Reinecke, U., Butà, M., Federspiel, S., Maier, H., Abdel-mohsen, M., Abdel-moneim, M., Reynolds, G. P., Sardar, A. M., Eggett, C. J., Rosario, P., de la Morena, E., José Barro, M., Rossini, P. M., Roth, J., Růžička, E., Svobodová, I., Mečíř, P., Jech, R., Remeš, F., Kleinschroth, A., Schliebs, R., Roßner, S., Heider, M., Schubert, H., König, P., Schuttes, H., HaveIec, L., Schwartz, J. -C., Sendtner, M., Smith, A., Li, M., Griesbeck, O., Parsadanian, A., Holtmann, B., Carroll, P., Toyka, K. V., Thoenen, H., Sharkawy, A. A., Ibrahim, T. A., Pulkowski, U., Siesjö, B. K., Klessaschek, M., Sopper, S., Demuth, M., Dörries, R., Hemm, S., Stahl-Hennig, C., Brinkmann, R., ter Meulen, V., Sperk, G., Schwarzer, C., Stern, G., Storm, G., Strein, I., Struck, M., Stürenburg, H. J., Kunze, K., Svadovsky, A. I., Morgunov, K. V., Peresedov, V. V., Moshkin, A. V., Teherani, D. K., Baumer, A., Rösier, M., Rösler, M., Wiesbeck, G. A., Wodarz, N., Boning, J., Timerbaeva, S. L., Alekseeva, N. S., Toso, A., Barletta, D., Tuulik, V., Lossmann, E., Raja, A., Meister, A., Uitti, R. J., Rajput, A. H., Ahlskog, J. E., Offord, K. P., Schroeder, D. R., O'Brien, P. C., Vaglini, F., Fascetti, F., Pardini, C., Mancino, L., Velbinger, K., Hartmann, H., Eckert, A., Grüter, S., Behrens, S., Niemann, J., Guschelbauer, B., Lauk, M., Wissel, J., Poewe, W., Wurthman, C., Janzen, E. N. H., Goping, G., Adegemo, O. M., Gemma, A., Kuijpers, J., Pollard, H. B., Zielke, B., Ziemann, U., and Bruns, D.
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- 1995
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3. Molecular and phenotypic characteristics of metachromatic leukodystrophy patients from Poland
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Ługowska, A, Berger, J, Tylki-Szymańska, A, Löschl, B, Molzer, B, Zobel, M, and Czartoryska, B
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- 2005
4. High prevalence of I179S mutation in patients with late-onset metachromatic leukodystrophy
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Lugowska, A, Berger, J, Tylki-Szymañska, A, Czartoryska, B, Löschl, B, and Molzer, B
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- 2002
5. Refsumʼs disease in an Arabian family
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FERTL, E, FÖLDY, D, VASS, K, AUFF, E, VASS, C, MOLZER, B, and BERNHEIMER, H
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- 2001
6. PHENOTYPE CHARACTERISTICS OF METACHROMATIC LEUKODYSTROPHY WITH HOMOZYGOSITY FOR ARYLSULFATASE A MUTATION P426L
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Berger, J, Bernheimer, H, Baumann, N, Turpin, J C, and Molzer, B.
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- 1997
7. Selektives Screening zur Erfassung peroxisomaler Erkrankungen
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Stöckler, S., primary, Ipsiroǧlu, O. S., additional, Molzer, B., additional, and Paschke, E., additional
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- 1990
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8. METACHROMATIC LEUKODYSTROPHY: NEW INSIGHTS INTO OCCURRENCE, DISTRIBUTION, AND PHENOTYPE RELATIONS OF ARYLSULFATASE A MUTATIONS
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Berger, J., Löschl, B., Bernheimer, H., Lugowska, A., Tylki-Szymanska, A., Gieselmann, V., and Molzer, B.
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- 1996
9. Adulte metachromatische Leukodystrophie unter dem Bild einer schizophrenen Psychose
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Kothbauer, P., Jellinger, K., Gross, H., Molzer, B., and Bernheimer, H.
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- 1977
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10. Adrenoleukodystrophy in an adult female: A clinical, morphological, and neurochemical study
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Schlote, W., Molzer, B., Peiffer, J., Poremba, M., Schumm, F., Harzer, K., Schnabel, R., and Bernheimer, H.
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- 1987
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11. Multiple sclerosis-like syndrome in a woman heterozygous for adrenoleukodystrophy
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Millner M, Ebner F, Molzer B, Moser Hw, Sylvia Stöckler, and Körner E
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Adult ,Pathology ,medicine.medical_specialty ,Heterozygote ,Multiple Sclerosis ,Diagnostico diferencial ,Asymptomatic ,Diagnosis, Differential ,Blurred vision ,medicine ,Humans ,Brain magnetic resonance imaging ,MULTIPLE SCLEROSIS-LIKE SYNDROME ,Adrenoleukodystrophy ,Evoked Potentials ,Cerebral white matter ,business.industry ,Multiple sclerosis ,Fatty Acids ,Fibroblasts ,medicine.disease ,Magnetic Resonance Imaging ,Neurology ,Female ,Neurology (clinical) ,medicine.symptom ,business - Abstract
A 28-year-old asymptomatic woman was diagnosed to be heterozygous for adrenoleukodystrophy (ALD) by elevated very long-chain fatty acids in serum and fibroblasts after ADL had been diagnosed in her son. A year later she had transient unilateral blurred vision. Evoked potentials and brain magnetic resonance imaging showed further separate cerebral white matter lesions suggesting multiple sclerosis (MS). MS-like syndromes in women heterozygous for ALD may be more frequent than previously recognized.
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- 1993
12. Adrenoleukodystrophy-Related Protein Can Compensate Functionally for Adrenoleukodystrophy Protein Deficiency (X-ALD): Implications for Therapy
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Netik, A., primary, Forss-Petter, S., additional, Holzinger, A., additional, Molzer, B., additional, Unterrainer, G., additional, and Berger, J., additional
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- 1999
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13. Association of X-Linked Adrenoleukodystrophy with HLA DRB1 Alleles
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Berger, J., primary, Bernheimer, H., additional, Fae, I., additional, Braun, A., additional, Roscher, A., additional, Molzer, B., additional, and Fischer, G., additional
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- 1995
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14. X-Linked Adrenoleukodystrophy (ALD): A Novel Mutation of the ALD Gene in 6 Members of a Family Presenting with 5 Different Phenotypes
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Berger, J., primary, Molzer, B., additional, Fae, I., additional, and Bernheimer, H., additional
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- 1994
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15. Multiple Sclerosis-Like Syndrome in a Woman Heterozygous for Adrenoleukodystrophy
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Stöckier, S., primary, Millner, M., additional, Molzer, B., additional, Ebner, F., additional, Körner, E., additional, and Moser, H.W., additional
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- 1993
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16. Metachromatic leukodystrophy (MLD): Phenotype and genotype in late onset cases
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Molzer, B., primary, Gieselmann, V., additional, Stöckler, S., additional, Zobel, M., additional, Minauf, M., additional, Reisecker, F., additional, Freimüller, M., additional, Artner, V., additional, and Bernheimer, H., additional
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- 1992
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17. X-linked Adrenoleukodystrophy: Unusual Clinical Manifestation.
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Angelova, L., Michaylova, E., Stephanova, E., Ivanova, M., Molzer, B., and Kremensky, I.
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- 2001
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18. Elevated Sulfatide Excretion in Compound Heterozygotes of Metachromatic Leukodystrophy and ASA-Pseudodeficiency Allele
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Lugowska, A., Tylki-Szymanska, A., Berger, J., and Molzer, B.
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- 1997
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19. [Mucopolysaccharidosis V (Ullrich-Scheie syndrome) (author's transl)]
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Kovarik J, Vormittag W, Gebhart W, Ruthner U, Gert Lubec, and Molzer B
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Male ,Iduronidase ,Adolescent ,Mucopolysaccharidosis I ,Humans ,Mucopolysaccharidoses ,Glycosaminoglycans ,Skin - Abstract
Mucopolysaccharidosis V (Scheie's syndrome, MPS-IS) is a very rare, autosomal recessively inherited metabolic disease. The degradation of dermatan sulphate and heparan sulphate is disturbed due to alpha-L-iduronidase deficiency, leading to intracellular storage and excessive urinary secretion of these substances. The characteristic clinical features are contractures (claw-like flexion of the fingers), umbilical and inguinal herniae, corneal opacity, hepatomegaly, myocardiopathy and minor skeletal malformations. A patient with Scheie's syndrome is now reported for the first time in Austria; the results of the clinical, biochemical, chromosomal, dermatoglyphic and electron optical investigations are described and discussed.
20. Giant platelets in erucic acid therapy for adrenoleukodystrophy.
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Stöckler, S, Molzer, B, Plecko, B, Zenz, W, Muntean, W, Söling, U, Hunneman, D H, Korenke, C, and Hanefeld, F
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UNSATURATED fatty acids , *ADRENOLEUKODYSTROPHY , *BLOOD cell count , *BLOOD platelets , *BLOOD platelet aggregation , *PLATELET function tests , *THERAPEUTICS - Published
- 1993
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21. Thyroid hormone induction of the adrenoleukodystrophy-related gene (ABCD2).
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Fourcade S, Savary S, Gondcaille C, Berger J, Netik A, Cadepond F, El Etr M, Molzer B, and Bugaut M
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- Animals, Astrocytes metabolism, Cells, Cultured, Chemokine CCL17, Chemokine CCL22, Chemokines, CC genetics, Gene Expression, Humans, Liver metabolism, Male, Mice, Mice, Knockout, Oligodendroglia metabolism, Rats, Rats, Sprague-Dawley, Receptors, Retinoic Acid metabolism, Receptors, Thyroid Hormone metabolism, Repetitive Sequences, Nucleic Acid, Retinoid X Receptors, Transcription Factors metabolism, Up-Regulation, Adrenoleukodystrophy genetics, Chemokines, CC biosynthesis, Promoter Regions, Genetic physiology, Thyroid Hormones biosynthesis, Triiodothyronine physiology
- Abstract
X-linked adrenoleukodystrophy (X-ALD) is a demyelinating disorder associated with impaired very-long-chain fatty-acid (VLCFA) beta-oxidation caused by mutations in the ABCD1 (ALD) gene that encodes a peroxisomal membrane ABC transporter. ABCD2 (ALDR) displays partial functional redundancy because when overexpressed, it is able to correct the X-ALD biochemical phenotype. The ABCD2 promoter contains a putative thyroid hormone-response element conserved in rodents and humans. In this report, we demonstrate that the element is capable of binding retinoid X receptor and 3,5,3'-tri-iodothyronine (T3) receptor (TRbeta) as a heterodimer and mediating T3 responsiveness of ABCD2 in its promoter context. After a T3 treatment, an induction of the ABCD2 gene was observed in the liver of normal rats but not that of TRbeta-/- mice. ABCD2 was not induced in the brain of the T3-treated rats. However, we report for the first time that induction of the ABCD2 redundant gene is feasible in myelin-producing cells (differentiated CG4 oligodendrocytes). The induction was specific for this cell type because it did not occur in astrocytes. Furthermore, we observed T3 induction of ABCD2 in human and mouse ABCD1-deficient fibroblasts, which was correlated with normalization of the VLCFA beta-oxidation. Finally, ABCD3 (PMP70), a close homolog of ABCD2, was also induced by T3 in the liver of control rats, but not that of TRbeta-/- mice, and in CG4 oligodendrocytes.
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- 2003
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22. Investigations of micro-organic brain damage (MOBD) in heterozygotes of metachromatic leukodystrophy.
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Tylki-Szymańska A, Ługowska A, Chmielik J, Kotowicz J, Jakubowska-Winecka A, Zobel M, Berger J, and Molzer B
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- Adult, Brain Diseases etiology, Cerebroside-Sulfatase blood, Cerebroside-Sulfatase genetics, DNA genetics, Female, Gene Frequency, Genotype, Heterozygote, Humans, Leukodystrophy, Metachromatic complications, Leukodystrophy, Metachromatic enzymology, Male, Middle Aged, Neuropsychological Tests, Sulfoglycosphingolipids urine, beta-Galactosidase blood, Brain Diseases pathology, Leukodystrophy, Metachromatic genetics
- Abstract
Potential damage of central and peripheral nervous system expressed as micro-organic brain damage (MOBD) was investigated in 27 unrelated heterozygotes with metachromatic leukodystrophy (MLD). Arylsulfatase A (ARSA) was determined in peripheral blood leukocytes and sulfatide excretion was estimated in 24-hour urine collections. Genomic DNA was analyzed for the ARSA pseudodeficiency (PD) allele by a PCR method. Clinical investigations included examination of hyper-reflexia, Babinski reflex, Wechsler Adult Intelligence Scale, Benton test, evoked potentials, and nerve conduction velocity (NCV). In our study, a higher incidence of evident or possible micro-organic brain damage was observed in true MLD/PD and MLD heterozygotes (NO/MLD, where NO means the wild allele) than in controls. On the basis of the Benton test, MOBD was suggested or indicated in 67% of MLD heterozygotes, 50% of MLD/PD heterozygotes, and 26% of controls. In our small group of carriers with MLD and PD mutations, persons NO/MLD(PD) with one wild-type allele did not show MOBD and displayed higher ARSA/beta-galactosidase ratios, unlike true MLD/PD compound heterozygotes who carry MLD-causing mutation in one allele and the ARSA-PD polymorphism in the second. Theoretically, this is a shift from autosomal recessive to autosomal dominant-like inheritance, especially when one cannot exclude the influence of polymorphisms (like ARSA-PD) in the wild allele. Since all psychological tests were age-matched, it can be assumed that the MOBD observed in MLD carriers does not have a progressive character unlike in MLD patients. However, it should be mentioned that MOBD appears to have no overt clinical consequences., (Copyright 2002 Wiley-Liss, Inc.)
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- 2002
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23. A de novo adrenoleukodystrophy gene (ABCD1) mutation S636I without detectable ABCD1 protein and a R104C mutation with normal amounts of protein from an Austrian patient collective.
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Berger J, Korosec T, Unterrainer G, and Molzer B
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- ATP Binding Cassette Transporter, Subfamily D, ATP Binding Cassette Transporter, Subfamily D, Member 1, ATP-Binding Cassette Transporters genetics, Adrenal Insufficiency genetics, Adult, Arginine genetics, Cysteine genetics, Humans, Isoleucine genetics, Serine genetics, Adrenoleukodystrophy genetics, Amino Acid Substitution genetics, Mutation, Missense genetics, Proteins analysis, Proteins genetics
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- 2000
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24. Co-expression of mutated and normal adrenoleukodystrophy protein reduces protein function: implications for gene therapy of X-linked adrenoleukodystrophy.
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Unterrainer G, Molzer B, Forss-Petter S, and Berger J
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- ATP Binding Cassette Transporter, Subfamily D, Member 1, ATP-Binding Cassette Transporters chemistry, Adrenoleukodystrophy genetics, Blotting, Western, Doxycycline pharmacology, Fatty Acids chemistry, Fatty Acids metabolism, Female, Fibroblasts, Flow Cytometry, Fluorescent Antibody Technique, Indirect, Gene Expression drug effects, HeLa Cells, Humans, Male, Membrane Proteins chemistry, Molecular Sequence Data, Oxidation-Reduction, Peroxisomes metabolism, Protein Conformation, RNA, Messenger analysis, RNA, Messenger genetics, Transfection, ATP-Binding Cassette Transporters genetics, ATP-Binding Cassette Transporters metabolism, Adrenoleukodystrophy therapy, Genetic Linkage genetics, Genetic Therapy, Membrane Proteins genetics, Membrane Proteins metabolism, Point Mutation genetics, X Chromosome genetics
- Abstract
Inherited defects in the X-chromosomal adrenoleukodystrophy (ALD; ABCD1) gene are the genetic cause of the severe neurodegenerative disorder X-linked adrenoleukodystrophy (X-ALD). Biochemically the accumulation of very long-chain fatty acids, caused by impaired peroxisomal beta-oxidation, is the pathognomonic characteristic of the disease. Due to the X-chromosomal inheritance of X-ALD no data are available to clarify the question whether mutated adrenoleukodystrophy proteins (ALDPs) can negatively influence normal ALDP function. Here we show that restoration of beta-oxidation in X-ALD fibroblasts following transient transfection with normal ALD cDNA is more effective in ALDP-deficient fibroblasts compared with fibroblasts expressing normal amounts of mutated ALDP. Furthermore, we utilized the HeLa Tet-on system to construct a stable HeLa cell line expressing a constant level of endogenous ALDP and doxycycline-inducible levels of mutated ALDP. The induction was doxycycline dosage-dependent and the ALDP correctly localized. Interestingly, although mutated ALDP increased >6-fold in a dosage-dependent manner the total amount of ALDP (mutated and normal) remained approximately even as demonstrated by western blot and flow cytometric analyses. Thus, apparently mutated and normal ALDP compete for integration into a limited number of sites in the peroxisomal membrane. Consequently, increased amounts of mutated ALDP resulted in decreased peroxisomal beta-oxidation and accumulation of very long-chain fatty acids. These findings have direct implications on future gene therapy approaches for treatment of X-ALD, since in some patients a non-functional endogenous protein could act in a dominant negative way or displace the introduced, normal protein.
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- 2000
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25. Prevalence of arylsulfatase A pseudodeficiency allele in metachromatic leukodystrophy patients from Poland.
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Lugowska A, Czartoryska B, Tylki-Szymańska A, Bisko M, Zimowski JG, Berger J, and Molzer B
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- Female, Humans, Poland epidemiology, Prevalence, Alleles, Cerebroside-Sulfatase deficiency, Cerebroside-Sulfatase genetics, Leukodystrophy, Metachromatic epidemiology, Leukodystrophy, Metachromatic genetics
- Abstract
Arylsulfatase A (ASA) pseudodeficiency (PD) allele was searched for in 22 patients originating from Poland and suffering from different types of metachromatic leukodystrophy (MLD). Four of them carried the PD allele in a heterozygous state. The prevalence of the PD allele among investigated MLD patients was revealed to be 9%, while the frequency of the PD allele in healthy controls was estimated at 6-7%. One of the examined MLD patients was additionally a carrier of an isolated mutation leading to the loss of the N-glycosylation site. The question arises whether and how MLD mutations create a convenient milieu for PD mutations to occur (or inversely)., (Copyright 2000 S. Karger AG, Basel)
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- 2000
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26. Coincidence of two novel arylsulfatase A alleles and mutation 459+1G>A within a family with metachromatic leukodystrophy: molecular basis of phenotypic heterogeneity.
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Berger J, Gmach M, Mayr U, Molzer B, and Bernheimer H
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- Adolescent, Cerebroside-Sulfatase urine, Child, Child, Preschool, Fatal Outcome, Female, Heterozygote, Humans, Leukodystrophy, Metachromatic urine, Male, Pedigree, Phenotype, Sequence Analysis, DNA, Alleles, Cerebroside-Sulfatase genetics, Leukodystrophy, Metachromatic genetics, Point Mutation genetics
- Abstract
In a family with three siblings, one developed classical late infantile metachromatic leukodystrophy (MLD), fatal at age 5 years, with deficient arylsulfatase A (ARSA) activity and increased galactosylsulfatide (GS) excretion. The two other siblings, apparently healthy at 12(1/2) and 15 years, respectively, and their father, apparently healthy as well, presented ARSA and GS values within the range of MLD patients. Mutation screening and sequence analysis disclosed the involvement of three different ARSA mutations being the molecular basis of intrafamilial phenotypic heterogeneity. The late infantile patient inherited from his mother the frequent 0-type mutation 459+1G>A, and from his father a novel, single basepair microdeletion of guanine at nucleotide 7 in exon 1 (7delG). The two clinically unaffected siblings carried the maternal mutation 459+1G>A and, on their paternal allele, a novel cytosine to thymidine transition at nucleotide 2435 in exon 8, resulting in substitution of alanine 464 by valine (A464V). The fathers genotype thus was 7delG/A464V. Mutation A464V was not found in 18 unrelated MLD patients and 50 controls. A464V, although clearly modifying ARSA and GS levels, apparently bears little significance for clinical manifestation of MLD, mimicking the frequent ARSA pseudodeficiency allele. Our results demonstrate that in certain genetic conditions MLD-like ARSA and GS values need not be paralleled by clinical disease, a finding with serious diagnostic and prognostic implications. Moreover, further ARSA alleles functionally similar to A464V might exist which, together with 0-type mutations, may cause pathological ARSA and GS levels, but not clinical outbreak of the disease.
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- 1999
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27. Targeted inactivation of the X-linked adrenoleukodystrophy gene in mice.
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Forss-Petter S, Werner H, Berger J, Lassmann H, Molzer B, Schwab MH, Bernheimer H, Zimmermann F, and Nave KA
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- ATP Binding Cassette Transporter, Subfamily D, Member 1, ATP-Binding Cassette Transporters biosynthesis, Adrenal Cortex metabolism, Adrenal Cortex pathology, Adrenoleukodystrophy pathology, Adrenoleukodystrophy physiopathology, Animals, Brain pathology, Child, Cloning, Molecular, Fatty Acids, Nonesterified metabolism, Genomic Library, Heterozygote, Humans, Kidney metabolism, Kidney pathology, Male, Membrane Proteins biosynthesis, Mice, Mice, Neurologic Mutants, Mice, Transgenic, Motor Activity, Testis metabolism, Testis pathology, ATP-Binding Cassette Transporters genetics, Adrenoleukodystrophy genetics, Brain metabolism, Membrane Proteins genetics, X Chromosome
- Abstract
In its severe form, X-linked adrenoleukodystrophy (ALD) is a lethal neurologic disease of children, characterized by progressive cerebral demyelination and adrenal insufficiency. Associated with a biochemical defect of peroxisomal beta-oxidation, very long-chain fatty acids (VLCFA) build up in tissues that have a high turnover of lipids, such as central nervous system (CNS) white matter, adrenal cortex, and testis. Whether the abnormal accumulation of VLCFA is the underlying cause of demyelination or merely an associated biochemical marker is unknown. ALD is caused by mutations in the gene for a peroxisomal membrane protein (ALDP) that shares structural features with ATP-binding-cassette (ABC) transporters. To analyze the cellular function of ALDP and to obtain an animal model of this debilitating disease, we have generated transgenic mice with a targeted inactivation of the ald gene. Motor functions in ALDP-deficient mice developed at schedule, and unexpectedly, adult animals appeared unaffected by neurologic symptoms up to at least 6 months of age. Biochemical analyses demonstrated impaired beta-oxidation in mutant fibroblasts and abnormal accumulation of VLCFAs in the CNS and kidney. In 6-month-old mutants, adrenal cortex cells displayed a ballooned morphology and needle-like lipid inclusions, also found in testis and ovaries. However, lipid inclusions and demyelinating lesions in the CNS were not a feature. Thus, complete absence of ALDP expression results in a VLCFA storage disease but does not impair CNS function of young adult mice by pathologic and clinical criteria. This suggests that additional genetic or environmental conditions must be fulfilled to model the early-onset and lethality of cerebral ALD in transgenic mice.
- Published
- 1997
- Full Text
- View/download PDF
28. [Adrenoleukodystrophy].
- Author
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Kálmánchey R, Molzer B, Illés Z, Princzinger A, and Sólyom J
- Subjects
- Adrenoleukodystrophy diagnosis, Adrenoleukodystrophy pathology, Adult, Child, Drug Combinations, Erucic Acids therapeutic use, Fatal Outcome, Female, Humans, Infant, Magnetic Resonance Imaging, Male, Tomography, X-Ray Computed, Triolein therapeutic use, Adrenoleukodystrophy genetics
- Abstract
7-year-old boy with adrenoleukodystrophy is presented with the typical clinical picture, biochemical findings and review of the literature. The obligate carrier status of the mother and the asymptomatic adrenoleukodystrophy of the 5-year-old brother are biochemically proved. Therapeutic regime of Lorenzo's oil has been introduced to the young brother, and the question of bone marrow transplantation is discussed.
- Published
- 1997
29. Occurrence, distribution, and phenotype of arylsulfatase A mutations in patients with metachromatic leukodystrophy.
- Author
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Berger J, Löschl B, Bernheimer H, Lugowska A, Tylki-Szymanska A, Gieselmann V, and Molzer B
- Subjects
- Adult, Alleles, Austria, Cerebroside-Sulfatase deficiency, Child, Child, Preschool, Female, Humans, Male, Phenotype, Poland, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Reference Standards, Cerebroside-Sulfatase genetics, Leukodystrophy, Metachromatic genetics, Mutation
- Abstract
Occurrence, distribution, and phenotype of arylsulfatase A (ASA) mutations were investigated in 27 patients with metachromatic leukodystrophy (MLD) from Central Europe, mainly from Austria (n = 15) and Poland (n = 9). Genomic DNA from leukocytes, fibroblasts, or paraffin-embedded, formalin-fixed brain or nerve tissue, respectively, was tested by natural or mutated primer-modulated PCR restriction, fragment length polymorphism for the eight most common European mutations: R84Q, S96F, 459+1G > A, I179S, A212V, 1204+1G > A, P426L, and 1401del11bp. The overall identification rate of unrelated MLD alleles was the highest, in adult (90%), medium in juvenile (50%), and lowest in late infantile (36%) MLD patients. The two common alleles, 459+1G > A and P426L, together accounted for 42% of all 50 unrelated MLD alleles investigated; I179S was observed in 6 of 50 MLD alleles (12%). Thus, I179S was far more frequent than hitherto thought and appears to be a third common mutation in Europe. Moreover, a different allelic distribution between Austrian and Polish juvenile patients was disclosed, indicating genetic heterogeneity of MLD even within Central Europe. The genotype-phenotype correlation suggested by Polten et al. [N Engl J Med 324:18-22, 1991] was not followed by all of our MLD patients. Moreover, some MLD patients with identical ASA mutations presented with different phenotypes. This may be due, at least in some cases, to the presence of an additional mutation on individual mutant alleles. Therefore, prediction of the clinical course from single mutation analysis is not possible.
- Published
- 1997
30. Late juvenile metachromatic leukodystrophy (MLD) in three patients with a similar clinical course and identical mutation on one allele.
- Author
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Tylki-Szymanska A, Berger J, Löschl B, Lugowska A, and Molzer B
- Subjects
- Adolescent, Adult, Cerebroside-Sulfatase metabolism, Female, Humans, Leukodystrophy, Metachromatic genetics, Leukodystrophy, Metachromatic physiopathology, Male, Mutagenesis, Pedigree, beta-Galactosidase metabolism, Alleles, Cerebroside-Sulfatase genetics, Leukodystrophy, Metachromatic enzymology
- Abstract
Metachromatic leukodystrophy (MLD) is an autosomal, recessively inherited, lysosomal storage disease caused by arylsulfatase A (ASA) activity deficit. Arylsulfatase A initiates the degradation of sulfatide (cerebroside sulfate), which is an essential component of myelin. The main clinical symptoms are caused by progressive demyelination. At least 34 MLD-related ASA mutations are known to date. I179S (E3P799) is a disease-related mutation, described for the first time by Fluharty in 1991. This aberration appears to substantially reduce, but not completely eliminate ASA activity, and was detected in individuals with late-onset (juvenile or adult) forms of MLD. This paper deals with the peculiar clinical course in three unrelated juveniles with late-onset MLD carrying the I179S mutations on one allele. In the three described patients with the I179S mutation, psychiatric disturbances and intellectual impairment dominated the clinical picture, while the neurological lesions progressed more slowly. Although the symptoms appeared rather early, making it possible to classify this as the juvenile type of MLD, the clinical picture was more that of the adult type. Although the mutations on the second allele in our patients are unknown, one can speculate, that the mutation I179S plays an important role in the characteristic clinical course (psychiatric impairment, slower neurological deterioration, but relatively early onset). It seems that I179S mutation on one allele with another mutation on the other allele reduces ASA activity, but the enzyme can still cope with a part of the substrate influx, leading to late-juvenile-onset MLD with such strikingly similar phenotypes remaining a little bit of the adult (psychiatric) type. This could be one more argument in favour of phenotype-genotype correlation in patients with MLD.
- Published
- 1996
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31. A new polymorphism of arylsulfatase A within the coding region.
- Author
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Berger J, Gmach M, Faé I, Molzer B, and Bernheimer H
- Subjects
- Alleles, Base Sequence, Child, DNA Primers, Heterozygote, Homozygote, Humans, Leukodystrophy, Metachromatic genetics, Male, Molecular Sequence Data, Mutation, Cerebroside-Sulfatase genetics, Polymorphism, Genetic
- Abstract
A 10-year-old boy with juvenile metachromatic leukodystrophy (MLD) presented with the 459 + 1G-->A arylsulfatase A (ASA) mutation on one allele. To detect his complete genotype, the other ASA allele was sequenced and a T-to-C transition at nucleotide 376 in exon 2 was identified. This missense mutation results in a substitution of leucine 76 by proline. Of 20 MLD unrelated controls, 18 carried the L/P76 mutation either in the homozygous (n = 6) or heterozygous (n = 12) state. The presence or absence of L/P76 did not influence leukocyte ASA activity or urinary sulfatide excretion. Apparently, the substitution of leucine 76 by proline is a common ASA polymorphism, neither being related to MLD nor creating ASA pseudodeficiency. However, because of its frequency and location, L/P76 may be of particular importance in genetic studies requiring the differentiation of the ASA alleles within a kindred. Further studies are directed to the as yet unresolved genotype of the index case with juvenile MLD.
- Published
- 1996
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32. Simultaneous detection of the two most frequent metachromatic leukodystrophy mutations.
- Author
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Berger J, Molzer B, Gieselmann V, and Bernheimer H
- Subjects
- Base Sequence, Brain pathology, Cells, Cultured, Cerebroside-Sulfatase genetics, DNA analysis, DNA Mutational Analysis, Female, Fibroblasts cytology, Genetic Markers, Humans, Leukocytes cytology, Male, Molecular Sequence Data, Pedigree, Polymerase Chain Reaction methods, Polymorphism, Restriction Fragment Length, Leukodystrophy, Metachromatic genetics, Point Mutation
- Abstract
Metachromatic leukodystrophy (MLD) is an autosomal recessive neurometabolic disorder caused by deficiency of arylsulfatase A (ASA). To detect ASA mutations E2S609 and E8P2382, the two most frequent MLD mutations, a non-radioactive polymerase chain reaction (PCR)-based assay was developed. This assay is a multiple "mutated primer-modulated PCR restriction fragment length polymorphism". The primers related to each mutation mismatch to create an XbaI or PstI restriction site in mutation E2S609 or E8P2382, respectively. The assay was designed to give four fragments of 160, 130, 100, and 70 bp, easy to distinguish. An internal control fragment is not necessary since both primer pairs amplify different regions of the ASA gene and fragments will be obtained in all allelic possibilities. This technique produced clear-cut results when genomic DNA, isolated either from leukocytes, cultured human fibroblasts, or paraffin-embedded autopsy material, was used as template. The assay will be of help in comparative studies on the relation between MLD genotype and phenotype, a problem not yet fully understood. Since our method was shown to work also on DNA from paraffin-embedded autopsy material, genotype/phenotype studies would not be restricted to in vivo investigations but could be done also on post mortem material, thus including investigations on a large group of cases and also studies on the relation between genotype and neuropathological features.
- Published
- 1993
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33. Unusual orthochromatic leukodystrophy with epitheloid cells (Norman-Gullotta): increase of very long chain fatty acids in brain discloses a peroxisomal disorder.
- Author
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Molzer B, Gullotta F, Harzer K, Poulos A, and Bernheimer H
- Subjects
- Adrenoleukodystrophy genetics, Aged, Aged, 80 and over, Brain Chemistry physiology, Cholesterol Esters metabolism, Fatty Acids analysis, Humans, Phytanic Acid metabolism, Adrenoleukodystrophy pathology, Brain pathology, Fatty Acids metabolism, Microbodies ultrastructure
- Abstract
Very long chain fatty acids (VLCFA) were found to be markedly increased and phytanic acid was borderline above normal in formalin-fixed brain white matter of case with an unusual type of familial leukodystrophy with epitheloid cells as described previously by Gullotta et al. [Neuropädiatrie (1970) 2: 173-186]. Increased VLCFA in brain clearly demonstrate that the patient had suffered from a peroxisomal disease. This diagnosis is corroborated by ultrastructural findings in brain showing typical lamellar inclusions. The particular type of peroxisomal disorder present in case (heterozygote of X-linked adrenoleukodystrophy?) remains speculative.
- Published
- 1993
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34. Multiple sclerosis-like syndrome in a woman heterozygous for adrenoleukodystrophy.
- Author
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Stöckler S, Millner M, Molzer B, Ebner F, Körner E, and Moser HW
- Subjects
- Adrenoleukodystrophy genetics, Adult, Diagnosis, Differential, Evoked Potentials, Fatty Acids metabolism, Female, Fibroblasts metabolism, Heterozygote, Humans, Magnetic Resonance Imaging, Adrenoleukodystrophy diagnosis, Multiple Sclerosis diagnosis
- Abstract
A 28-year-old asymptomatic woman was diagnosed to be heterozygous for adrenoleukodystrophy (ALD) by elevated very long-chain fatty acids in serum and fibroblasts after ADL had been diagnosed in her son. A year later she had transient unilateral blurred vision. Evoked potentials and brain magnetic resonance imaging showed further separate cerebral white matter lesions suggesting multiple sclerosis (MS). MS-like syndromes in women heterozygous for ALD may be more frequent than previously recognized.
- Published
- 1993
- Full Text
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35. Diagnosis of peroxisomal disorders with neurological involvement.
- Author
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Molzer B
- Subjects
- Adrenoleukodystrophy blood, Adrenoleukodystrophy diagnosis, Fatty Acids analysis, Humans, Infant, Newborn, Metabolism, Inborn Errors metabolism, Nervous System Diseases etiology, Nervous System Diseases metabolism, Phytanic Acid blood, Phytanic Acid metabolism, Zellweger Syndrome blood, Zellweger Syndrome diagnosis, Fatty Acids metabolism, Metabolism, Inborn Errors diagnosis, Microbodies metabolism, Nervous System Diseases diagnosis
- Abstract
Peroxisomal disorders are a group of inherited metabolic diseases caused by impairment of one or more peroxisomal functions. Ten disorders with neurological involvement have been recognized. Diagnosis and differentiation of these disorders is based on a number of important biochemical markers. For all disorders elevated values of very long chain fatty acids (VLCFA) and/or phytanic acid (PHYT) are important primary diagnostic parameters. Our results with regard to these two diagnostic markers are presented. VLCFA determined by gaschromatography in 414 samples (plasma, leukocytes or fibroblasts respectively) revealed increased values of hexacosanoic acid in 30 hemizygotes and 10 heterozygotes of adrenoleukodystrophy/adrenomyeloneuropathy and in eight infants with Zellweger disease or neonatal adrenoleukodystrophy. 15 cases with peroxisomal disorders were detected by VLCFA analysis in autopsy material. Gaschromatographic analysis of PHYT in plasma showed in some patients with Zellweger disease or neonatal adrenoleukodystrophy increase. In seven Refsum patients beside gaschromatographic demonstration of PHYT accumulation in plasma, analysis of plasma phytanyltriglycerides by thin-layer chromatography proved to be a rapid and reliable method for detection of patients and monitoring dietary treatment.
- Published
- 1993
36. [Zellweger syndrome, neonatal adrenoleukodystrophy or infantile Refsum's disease in a case with generalized peroxisome defect?].
- Author
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Schmitt K, Molzer B, Stöckler S, Tulzer G, and Tulzer W
- Subjects
- Adrenoleukodystrophy enzymology, Catalase blood, Fatty Acids blood, Humans, Infant, Male, Phytanic Acid blood, Plasmalogens biosynthesis, Refsum Disease enzymology, Zellweger Syndrome enzymology, Adrenoleukodystrophy diagnosis, Microbodies physiology, Refsum Disease diagnosis, Zellweger Syndrome diagnosis
- Abstract
An eleven month-old boy presented clinically with craniofacial dysmorphia, severe psychomotor retardation, neurological deterioration, no response to visual and acoustic stimuli, failure to thrive, hepatomegaly and adrenal insufficiency. Specific biochemical markers for a peroxisomal deficiency disorder (Zellweger's syndrome, neonatal adrenoleukodystrophy, infantile Refsum's disease) revealed pathological results for very long chain fatty acids, phytanic acid, pristanic acid, plasmalogen biosynthesis and catalase, thus confirming the clinical diagnosis. Comparison of clinical and biochemical findings in the patient with the characteristics of the three peroxisomal deficiency disorders showed overlapping with each of these disorders, which corresponds to the current view that these three peroxisomal disorders differ only with respect to onset and severity of the clinical manifestations, but not with regard to the biochemical defects.
- Published
- 1993
37. Elevated sulfatide excretion in heterozygotes of metachromatic leukodystrophy: dependence on reduction of arylsulfatase A activity.
- Author
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Molzer B, Sundt-Heller R, Kainz-Korschinsky M, and Zobel M
- Subjects
- Adult, Female, Heterozygote, Homozygote, Humans, Infant, Leukocytes enzymology, Leukodystrophy, Metachromatic enzymology, Leukodystrophy, Metachromatic urine, Male, Cerebroside-Sulfatase metabolism, Leukodystrophy, Metachromatic genetics, Sulfoglycosphingolipids urine
- Abstract
Sulfatide excretion in urine and arylsulfatase A (ASA) activity in leukocytes were determined in 10 homozygotes of metachromatic leukodystrophy (MLD), 7 obligate and 5 facultative MLD heterozygotes, 6 low ASA subjects (not related to MLD homozygotes), and in 9 controls. As compared to controls (sulfatides: 0-2 nmol/mg lipid; ASA: 101-287 nmol p-nitrocatechol/mg protein/hr), MLD homozygotes displayed highly increased sulfatide excretions (27-280 nmol) and low residual ASA activities (0-13 nmol). Of 12 MLD heterozygotes (ASA: 18-87 nmol) 10 showed increased sulfatides (3-24 nmol). All heterozygotes with ASA activity < 60 nmol (n = 8) had elevated sulfatide excretions (4-24 nmol). Thus, reduction of ASA activity below 40% of the mean value of controls seems to be the critical threshold for elevated sulfatide excretion in MLD heterozygotes. The low ASA subjects (ASA in the heterozygote range) excreted sulfatides in the control range, even those with ASA activities < 60 nmoles (n = 3; including a definite homozygote for ASA-pseudodeficiency; ASA:25 nmol). Statistical evaluation of sulfatide excretion and ASA activity in all subjects (n = 37) revealed a significant inverse relation (Spearman rank correlation; R = 0.8278, P < 0.001). The finding of elevated sulfatide excretion in certain MLD heterozygotes might point to increase of sulfatides also in the nervous system.
- Published
- 1992
- Full Text
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38. [Peroxisomal neurologic diseases and Refsum disease: very long chain fatty acids and phytanic acid as diagnostic markers].
- Author
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Molzer B, Stöckler S, and Bernheimer H
- Subjects
- Adolescent, Adrenoleukodystrophy blood, Adrenoleukodystrophy genetics, Adult, Child, Child, Preschool, Genetic Carrier Screening, Humans, Infant, Infant, Newborn, Neonatal Screening, Refsum Disease blood, Refsum Disease genetics, Zellweger Syndrome blood, Zellweger Syndrome genetics, Adrenoleukodystrophy diagnosis, Fatty Acids blood, Microbodies physiology, Phytic Acid blood, Refsum Disease diagnosis, Zellweger Syndrome diagnosis
- Abstract
Peroxisomal disorders are genetic metabolic diseases with generalized, multiple, or single functional disturbances of the peroxisome. According to the extent of the functional disturbances 3 groups of diseases can be differentiated: disorders with generalized loss of peroxisomal functions (Zellweger syndrome, ZS; neonatal adrenoleukodystrophy, NALD; infantile Refsum's disease), disorders with multiple enzymatic defects (e.g. rhizomelic chondrodysplasia punctata), and disorders with a single enzymatic defect in the peroxisome, the most important being adrenoleukodystrophy/adrenomyeloneuropathy (ALD/AMN). Adult Refsum's disease, a genetic neurological disorder with phytanic acid accumulation, is due to a mitochondrial enzyme deficiency, but is often considered together with peroxisomal diseases because of phytanic acid (PHYT) accumulation in most peroxisomal diseases. The main clinical and pathological criteria of the major disorders and the biochemical parameters of their differentiation are presented. Elevated levels of very long chain fatty acids (VLCFA) and/or PHYT are the primary diagnostic markers for all peroxisomal disorders and adult Refsum's disease, respectively. Our investigations disclosed 30 ALD/AMN hemizygotes, 16 ALD/AMN heterozygotes, 8 cases of ZS/NALD and 7 patients with adult Refsum's disease. In addition, 15 cases of peroxisomal disorders were confirmed by biochemical investigations in autopsy material. With regard to peroxisomal disorders, therapeutic concepts exist only for ALD/AMN: corticosteroid substitution for adrenal insufficiency, dietary treatment, and bone marrow transplantation (BMT). Adult Refsum's disease can be treated successfully by dietary therapy. In case of dietary treatment and BMT, assay of VLCFA and/or PHYT is important for the biochemical evaluation of these therapies.
- Published
- 1992
39. Di-, mono- and nonphytanyl triglycerides in the serum: a sensitive parameter of the phytanic acid accumulation in Refsum's disease.
- Author
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Molzer B, Bernheimer H, Barolin GS, Höfinger E, and Lenz H
- Subjects
- Humans, Refsum Disease diet therapy, Eicosanoic Acids blood, Phytanic Acid blood, Refsum Disease blood, Triglycerides blood
- Abstract
The relative proportions of the diphytanyl, monophytanyl and nonphytanyl triglycerides ("triglyceride pattern"), the phytanic acid content of the triglycerides and the phytanic acid levels in the serum of 3 patients with Refsum's disease (heredopathia atactica polyneuritiformis, phytanic acid storage disease) were estimated by thin-layer chromatography, densitometry and gas chromatography, respectively. The individual triglyceride patterns were clearly dependent on the phytanic acid content of the triglycerides: the more phytanic acid in the triglycerides, the higher the percentage of the diphytanyl and the lower the percentage of the nonphytanyl triglycerides. The monophytanyl triglycerides were also related to the phytanic acid content of the triglycerides, although in a complex manner. The triglyceride pattern can be taken as a parameter of the phytanic acid accumulation in Refsum's disease to be at least as sensitive as the serum phytanic acid level in the biochemical evaluation of the efficiency of the dietary treatment.
- Published
- 1979
- Full Text
- View/download PDF
40. Detection of GM2-gangliosidosis (Tay-Sachs and Sandhoff disease) gene carriers by serum hexosaminidase assay.
- Author
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Molzer B and Bernheimer H
- Subjects
- Diagnosis, Differential, G(M2) Ganglioside, Gangliosidoses enzymology, Heterozygote, Hexosaminidases deficiency, Homozygote, Humans, Lipidoses enzymology, Gangliosidoses diagnosis, Genes, Hexosaminidases blood, Lipidoses diagnosis
- Abstract
With a view to the biochemical detection of homo- and heterozygous carriers of GM2-gangliosidosis, serum hexosaminidase activities were investigated in patients from Tay-Sachs and from Sandhoff disease, respectively, in their relatives, and in normal controls. Two related methods for the differential determination of hexosaminidase A and B activities were tested. Homozygous carriers (patients) were detected by both methods in a similar manner. As regards the identification of heterozygous carriers more conclusive results were attained by the "heat inactivation method" (O'Brien, J.S., Okada, S., Chen, A. and Fillerup, D.L. (1970) New Engl. J. Med 283, 15).
- Published
- 1976
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41. [Course of Refsum's disease under diabetic treatment. Clinical, biochemical and neuropathological data (author's transl)].
- Author
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Lenz H, Sluga E, Bernheimer H, Molzer B, and Pürgyi W
- Subjects
- Female, Gait, Humans, Middle Aged, Movement Disorders diagnosis, Night Blindness diagnosis, Olfaction Disorders diagnosis, Pedigree, Speech Disorders diagnosis, Refsum Disease diet therapy
- Published
- 1979
42. Accumulation of very long chain fatty acids is common to 3 variants of adrenoleukodystrophy (ALD). "Classical" ALD, atypical ALD (female patient) and adrenomyeloneuropathy.
- Author
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Molzer B, Bernheimer H, Budka H, Pilz P, and Toifl K
- Subjects
- Addison Disease genetics, Addison Disease metabolism, Adult, Brain pathology, Child, Chromatography, Gas, Demyelinating Diseases genetics, Female, Genetic Variation, Humans, Male, Cholesterol Esters analysis, Demyelinating Diseases metabolism, Fatty Acids analysis
- Abstract
Fatty acids of cholesterol esters were analyzed by gas chromatography in affected CNS white matter of 3 variants of ALD ("classical" ALD, atypical ALD (adult female) and AMN) and of 10 controls with myelin breakdown of an etiology other than ALD. In all 3 ALD variants a marked accumulation of very long chain fatty acids (VLFA) as compared to control material was observed. This was due to the accumulation mainly of saturated C24-C32 fatty acids, particularly of C26:0, C25:0 and, to a lesser extent, C24:0 and C27:0 fatty acids. Our results demonstrate for the first time an accumulation of VLFA in an adult female patient (atypical ALD), who probably is an ALD heterozygote rather than a variant of AMN, and confirm and extend earlier findings in classical ALD and AMN, respectively. It appears that ALD may be a single nosological entity with clinically and morphologically different variants sharing specific ultrastructural (accumulation of paired leaflets) and neuro-biochemical (accumulation of VLFA) diagnostic markers.
- Published
- 1981
- Full Text
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43. Fatty acid patterns in brain, fibroblast, leukocyte and body fluid lipids in adrenoleukodystrophy.
- Author
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Molzer B, Bernheimer H, and Toifl K
- Subjects
- Adolescent, Body Fluids metabolism, Brain metabolism, Child, Cholesterol Esters metabolism, Fatty Acids, Nonesterified metabolism, Fibroblasts metabolism, Humans, Leukocytes metabolism, Myelin Proteins metabolism, Adrenal Insufficiency metabolism, Brain Diseases, Metabolic metabolism, Demyelinating Diseases metabolism, Fatty Acids metabolism
- Abstract
Fatty acid patterns of certain tissue and body fluid lipids of ALD and control cases were investigated by thin layer and gas chromatography. A high percentage (55.2%) of VLFA was found in the ALD brain white matter cholesterol esters; this was mainly due to increased proportions of 26:0, 25:0, 26:1 and greater than 26 C fatty acids. The percentage of VLFA in the white matter cholesterol esters of pathological controls with myelin breakdown of different etiology was low (0.4-7.1%). In the fibroblast total lipids of an ALD patient an increase of 26:0 and 25:0 fatty acids was found. Moderately increased proportions of hexacosanoic acid were observed in the leukocyte total lipids of 2 severely affected ALD patients, but not in a slightly as well as in a possible affected case. No accumulation of VLFA was detected in cholesterol ester, triglyceride and free fatty acid fractions in the CSF of an ALD patient and in ALD serum sphingomyelin. Our results substantiate the specificity of VLFA accumulation in the white matter cholesterol esters of ALD brain and lend some further evidence to the view that a generalized impairment of VLFA metabolism seems to be present in this disease.
- Published
- 1981
- Full Text
- View/download PDF
44. [Lipid storage diseases (lipidoses): genetic, biochemical and clinico-chemical aspects].
- Author
-
Bernheimer H and Molzer B
- Subjects
- Brain Diseases, Metabolic genetics, Child, Chromosome Mapping, Enzymes deficiency, Female, Genetic Carrier Screening, Homozygote, Humans, Lipid Metabolism, Inborn Errors diagnosis, Lipid Metabolism, Inborn Errors enzymology, Nervous System Diseases genetics, Pedigree, Pregnancy, Prenatal Diagnosis, Lipid Metabolism, Inborn Errors genetics
- Abstract
Lipidoses are genetic diseases due to disease-specific defects in the enzymatic catabolism of lipids, with accumulation of the respective lipid substrate in the nervous system and/or peripheral tissues. The clinical chemical diagnosis of lipidoses can be accomplished by demonstration of the enzyme defect and/or substrate accumulation in body fluids (urine, blood serum), leukocytes, cultured fibroblasts, amniotic fluid cells, or amniotic fluid, respectively. These assays are important with regard to: 1. the specific detection or exclusion of diseases, which are difficult to diagnose by their clinical presentation, 2. prenatal diagnoses, 3. detection of (clinically inconspicuous) heterozygotes (essential for individual genetic counselling), and 4. the biochemical control of dietary treatment in Refsum's disease.
- Published
- 1986
- Full Text
- View/download PDF
45. Phytanic acid and very long chain fatty acids in genetic peroxisomal disorders.
- Author
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Molzer B, Kainz-Korschinsky M, Sundt-Heller R, and Bernheimer H
- Subjects
- Adrenal Glands metabolism, Adrenoleukodystrophy genetics, Adrenoleukodystrophy metabolism, Brain metabolism, Cholesterol Esters metabolism, Fatty Acids analysis, Humans, Kidney metabolism, Lipid Metabolism, Inborn Errors genetics, Microbodies analysis, Phytanic Acid analysis, Refsum Disease genetics, Refsum Disease metabolism, Zellweger Syndrome genetics, Zellweger Syndrome metabolism, Eicosanoic Acids metabolism, Fatty Acids metabolism, Lipid Metabolism, Inborn Errors metabolism, Microbodies metabolism, Phytanic Acid metabolism
- Abstract
1. Phytanic acid, phytanyl-triacylglycerols, and very long chain fatty acids were analysed by gas chromatography or thin-layer chromatography in blood and tissues of patients with different genetic peroxisomal disorders (Refsum's disease, X-linked adrenoleukodystrophy, neonatal adrenoleukodystrophy, Zellweger syndrome). 2. We evaluated these analyses in the detection of patients with Refsum's disease, X-linked adrenoleukodystrophy, neonatal adrenoleukodystrophy, and Zellweger syndrome, and of carriers of X-linked adrenoleukodystrophy. In particular, the analysis of phytanyl-triacylglycerols by thin-layer chromatography proved to be a rapid and reliable method for the detection of patients and the monitoring of their dietary treatment in Refsum's disease. In X-linked adrenoleukodystrophy, carrier detection may depend on very long chain fatty acid analysis in more than one material (e.g. plasma and fibroblasts). 3. Analysis of phytanic acid showed that in patients with multiple impairments of peroxisomal functions (Zellweger syndrome, neonatal adrenoleukodystrophy) phytanic acid levels may be increased not only in serum, but also in the tissue (e.g. brain, adrenals, kidney). 4. Analysis of very long chain fatty acids in cholesterol esters from the brain, adrenals, kidney, and liver of patients with peroxisomal disorders revealed four different types of very long chain fatty acid patterns according to the behaviour of C 26:0 and of other saturated and monounsaturated very long chain fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1989
46. Detection of adrenoleukodystrophy by increased C26:0 fatty acid levels in leukocytes.
- Author
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Molzer B, Bernheimer H, Heller R, Toifl K, and Vetterlein M
- Subjects
- Adolescent, Adrenoleukodystrophy metabolism, Cells, Cultured, Child, Female, Fibroblasts metabolism, Humans, Male, Adrenoleukodystrophy genetics, Diffuse Cerebral Sclerosis of Schilder genetics, Fatty Acids metabolism, Genetic Carrier Screening methods, Leukocytes metabolism
- Abstract
Very long chain fatty acids of peripheral blood leukocytes were analyzed by gas chromatography in nine members of a family including two hemizygotes and one obligate heterozygote for adrenoleukodystrophy (ALD), as well as in twelve controls. Comparative investigations were done in cultured fibroblasts. Elevated C26:0 levels were observed in leukocytes and fibroblasts of ALD hemizygotes. The obligate heterozygote displayed a clear-cut increase of C26:0 concentration in leukocytes but not in fibroblasts. Determination of C26:0 in leukocytes may serve as diagnostic tool in the detection of ALD gene carriers.
- Published
- 1982
- Full Text
- View/download PDF
47. [Adrenoleukodystrophy and adrenomyeloneuropathy--changes in the immunoglobulins in the cerebrospinal fluid].
- Author
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Nevsímalová S, Safár J, Molzer B, Süssová J, and Prosková M
- Subjects
- Adrenoleukodystrophy genetics, Adrenoleukodystrophy immunology, Adult, Child, Female, Humans, Male, Middle Aged, Pedigree, Adrenoleukodystrophy cerebrospinal fluid, Diffuse Cerebral Sclerosis of Schilder cerebrospinal fluid, Immunoglobulin G cerebrospinal fluid
- Published
- 1987
48. [Mucopolysaccharidosis V (Ullrich-Scheie syndrome) (author's transl)].
- Author
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Kovarik J, Vormittag W, Gebhart W, Ruthner U, Lubec G, and Molzer B
- Subjects
- Adolescent, Glycosaminoglycans metabolism, Humans, Iduronidase metabolism, Male, Mucopolysaccharidosis I metabolism, Mucopolysaccharidosis I pathology, Skin ultrastructure, Mucopolysaccharidoses diagnosis, Mucopolysaccharidosis I diagnosis
- Abstract
Mucopolysaccharidosis V (Scheie's syndrome, MPS-IS) is a very rare, autosomal recessively inherited metabolic disease. The degradation of dermatan sulphate and heparan sulphate is disturbed due to alpha-L-iduronidase deficiency, leading to intracellular storage and excessive urinary secretion of these substances. The characteristic clinical features are contractures (claw-like flexion of the fingers), umbilical and inguinal herniae, corneal opacity, hepatomegaly, myocardiopathy and minor skeletal malformations. A patient with Scheie's syndrome is now reported for the first time in Austria; the results of the clinical, biochemical, chromosomal, dermatoglyphic and electron optical investigations are described and discussed.
- Published
- 1978
49. [Clinical and biochemical follow up of Refsum's disease (author's transl)].
- Author
-
Barolin GS, Hodkewitsch E, Höfinger E, Scholz H, Bernheimer H, and Molzer B
- Subjects
- Adult, Cerebrospinal Fluid Proteins analysis, Electromyography, Female, Heterozygote, Humans, Pedigree, Phytanic Acid blood, Phytol, Refsum Disease blood, Refsum Disease cerebrospinal fluid, Refsum Disease diet therapy, Refsum Disease genetics, Triglycerides blood, Refsum Disease diagnosis
- Abstract
Within a family refered here, two sisters are presenting heredopathia atactica polyneuritiformis (Morbus Refsum) with the complete clinical, electromyographical and serological findings (increased phytanic acid level, accumulation of mono- and diphytanyl, triglycerides). In addition, some symptoms of Refsum's disease are clinically apparent in the eight year old daughter of one of the patients, but significant principal characteristics are absent (dissociation of the spinal fluid, retinopathia pigmentosa, increased phytanic acid level). The phytanic acid level in the serum of ten clinically normal blood relations (three of which are also obligatory heterozygotes) is normal. In both patients with manifest illness we found not only the usual spinal fluid changes with highly increased protein levels (gammaglobulin, IgA- and IgG-fraction) but also a remarkably large number of macrophages with vacuoles. Within almost two years of keeping to a strict diet with low phytanic acid and phytol content, both patients showed a distinct clinical improvement in parallel with a decrease of the phytanic acid level. Even a temporary increase of the phytanic acid level in one of the patients did not cause clinical relapse. Regarding the biochemical control of the course of the disease, the phytanic acid containing triglycerides proved to be a highly sensitive parameter.
- Published
- 1979
50. Sandhoff disease: ganglioside G(M2) and asialo-G(M2) accumulation in the cerebrospinal fluid.
- Author
-
Bernheimer H, Molzer B, and Deisenhammer E
- Subjects
- G(M2) Ganglioside analogs & derivatives, Humans, Infant, Male, Sialic Acids, G(M2) Ganglioside cerebrospinal fluid, Gangliosides cerebrospinal fluid, Gangliosidoses cerebrospinal fluid
- Published
- 1977
- Full Text
- View/download PDF
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