Publications by authors named "Piotr Sokolowski"

4 Publications

  • Page 1 of 1

The cystathionine beta-synthase variant c.844_845ins68 protects against CNS demyelination in X-linked adrenoleukodystrophy.

Hum Mutat 2006 Oct;27(10):1063-4

University Hospital Bonn, Department of Neurology, Bonn, Germany.

The clinical course of X-linked adrenoleukodystrophy (X-ALD) is of unexplained heterogeneity. Major X-ALD phenotypes are the progressive childhood cerebral form (CCALD) with early confluent cerebral demyelination and the adult-onset adrenomyeloneuropathy (AMN). Adult AMN may present with demyelinated foci of the CNS (adrenoleukomyeloneuropathy, ALMN) or without ("pure" AMN). Activated methionine is essential for CNS myelination, and methionine metabolism is important for glutathione synthesis, which may influence neurodegeneration. Cystathionine beta-synthase (CBS) is a key enzyme of methionine metabolism. The CBS variant c.844_845ins68 (p.-) may influence the availability of activated methionine as well as of glutathione. In this study, we analyzed this variant in genomic DNA samples of 86 X-ALD patients. We observed the allele carrying the insertion in 12 of 49 patients without CNS demyelination ("pure" AMN), but in none of the 37 patients with CNS demyelination (CCALD or ALMN; chi(2)=10.531; p=0.001). We conclude that the insertion allele of CBS c.844_845ins68 protected X-ALD patients against CNS demyelination in our study sample. These data suggest that the individual conditions in methionine metabolism may be a disease modifier of X-ALD. Since methionine metabolism can easily be influenced by vitamin and amino acid substitution, this observation could be a basis of novel treatment strategies in this yet untreatable disease. (c) 2006 Wiley-Liss, Inc.
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http://dx.doi.org/10.1002/humu.9459DOI Listing
October 2006

Adrenal steroids in adrenomyeloneuropathy. Dehydroepiandrosterone sulfate, androstenedione and 17alpha-hydroxyprogesterone.

J Neurol 2005 Dec;252(12):1525-9

Universitaetsklinikum Bonn, Institut für Klinische Biochemie, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.

Adrenoleukodystrophy (ALD) and its adult variant adrenomyeloneuropathy (AMN) are X-linked diseases associated with a deficiency in the peroxisomal degradation of saturated very long chain fatty acids (VLCFA) resulting in an accumulation of VLCFA in the central and peripheral myelin, the adrenal cortex and the testis. Adrenal insufficiency with clinical hypocortisolism occurs in approximately two thirds of the patients with AMN. We studied the circulating adrenal hormones 17alpha-hydroxyprogesterone (17alpha-OHP), androstenedione and dehydroepiandrosterone sulphate (DHEAS) in 63 male AMN patients (age 17-65 years) and the DHEAS serum levels in 95 healthy male controls (age 30-65 years). 34 of the patients presented with the phenotype of only spinal cord and peripheral nerve disability without hypocortisolism, 29 of the patients presented with the phenotype of either additional hypocortisolism or Addison's syndrome only. Normal 17alpha-OHP concentrations were found in all patients with no significant difference between patients without and with hypocortisolism (6.07 +/- 0.61 nmol/l and 4.76 +/- 0.37 nmol/l). Androstenedione concentration was significantly (p < 0.01) lower in patients with hypocortisolism (2.99 +/- 0.65 pmol/l versus 5.71 +/- 0.68 pmol/l). As serum levels of DHEAS are agedependent we divided the two groups into two subgroups each (subgroup one: age 17-40 years, subgroup two: age 41-65 years). The DHEAS concentration of patients without and with hypocortisolism was significantly (p < 0.01) lower in both subgroups (1. 4.35 +/- 0.84 micromol/l, n = 15, 2. 15 +/- 0.28 micromol/l, n = 19; 1. 1.90 +/- 0.57 micromol/, n = 21, 2. 0.96 +/- 0.29 micromol/l, n = 8) compared to controls (1. 9.0 +/- 0.96 micromol/l; 2. 5.21 +/- 0.25 micromol/l). In conclusion, androstenedione and DHEAS serum concentrations are subnormal in all AMN patients and may therefore serve as sensitive markers of the adrenal function in adrenomyeloneuropathy.
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http://dx.doi.org/10.1007/s00415-005-0908-7DOI Listing
December 2005

Genetic variations and humoral immune responses to myelin oligodendroglia glycoprotein in adult phenotypes of X-linked adrenoleukodystrophy.

J Neuroimmunol 2003 Feb;135(1-2):148-53

Department of Neurology, University of Bonn, Sigmund-Freud-Str. 20, 53105, Bonn, Germany.

The lack of phenotype/genotype association in X-linked adrenoleukodystrophy (X-ALD) has prompted the search for disease modifying factors. We previously demonstrated increased serum antibody responses against myelin oligodendrocyte glycoprotein (MOG) in various clinical phenotypes of X-ALD allowing speculations that myelin specific humoral immune responses might be involved in phenotype generation of X-ALD. In the present study, we investigated the possible association of (1) a naturally occurring variable number tandem repeat (vntr) polymorphism (C allele) in the 3' flanking region of the interleukin-6 gene (IL-6), previously demonstrated to modify the course of Alzheimer's disease, systemic lupus erythematodes and Multiple Sclerosis (MS), (2) a tetranucleotide repeat polymorphism (TAAA)(n) in the 3' flanking region of the MOG gene and (3) HLA class II alleles with adult clinical phenotypes and serum antibody responses to MOG in 70 adult X-ALD patients. HLA class II alleles, (TAAA)(n) MOG gene polymorphisms, and IL-6 C allele were not associated with clinical phenotypes. Anti-MOG antibodies were detectable in 17/54 X-ALD patients (31.5%). Anti-MOG antibodies were associated with the 226 bp (TAAA)(n) MOG gene polymorphism but not with distinct clinical phenotypes.
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http://dx.doi.org/10.1016/s0165-5728(02)00445-9DOI Listing
February 2003