1/4. Severe sensory ataxia and demyelinating polyneuropathy with IgM anti-GM2 and GalNAc-GD1A antibodies.Several polyneuropathy syndromes have been described with polyclonal serum immunoglobulin g (IgG) or immunoglobulin m (IgM) binding to gangliosides GM2 and GalNAc-GD1a that contain the terminal trisaccharide moiety GalNAc(beta1-4)Gal(alpha2-3)NeuAc. We describe the clinical and electrodiagnostic features in two patients with serum IgM monoclonal anti-GM2 and anti-GalNAc-GD1a antibodies. These patients had slowly progressive, panmodal sensory loss with severe sensory ataxia. Electrodiagnostic testing showed demyelinating features. Prominent improvement in gait ataxia occurred after treatment with human immune globulin but not after other immunomodulating therapies. Enzyme-linked immunoabsorbent assay and thin-layer chromatography demonstrate that the patient's serum monoclonal IgM bound to gangliosides GM2 and GalNac-GD1a but not to gangliosides without the GalNAc(beta1-4)Gal(alpha2-3)NeuAc moiety. This neuropathy differs from previously reported neuropathy syndromes associated with polyclonal GM2 and GalNAc-GD1a antibodies and from other chronic demyelinating polyneuropathies. We conclude that a distinct syndrome of chronic demyelinating neuropathy with sensory ataxia, unresponsive to corticosteroids, is associated with monoclonal IgM binding to gangliosides with a terminal GalNAc(beta1-4)Gal(alpha2-3)NeuAc trisaccharide moiety. diagnosis of this syndrome is important to direct appropriate treatment.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
2/4. Ataxic polyneuropathy and anti-Pr2 IgM kappa M proteinemia.A case of ataxic neuropathy associated with IgM kappa M proteinemia is reported. Double filtration plasmapheresis effectively treated the neuropathy. The IgM kappa antibody had anti-Pr2 cold agglutinin activity. We demonstrated reactivities of the IgM kappa antibody to sialosyl paragloboside, sialosyl lactosaminyl paragloboside, GT1b, GD1a, GD1b, GM3 and GD3 on high-performance thin-layer chromatography immunostaining and enzyme-linked immunosorbent assay, which is previously unreported antigenic specificity of the M proteins in cases of paraproteinemic neuropathy. IgM M protein with anti-Pr2 cold agglutinin activity may play a pathogenetic role in peripheral nerve demyelination, because the target antigens of the M protein are present in myelin and possibly in endothelial cells of the peripheral nervous system.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
3/4. Prenatal detection of Salla disease based upon increased free sialic acid in amniocytes.Salla disease is an autosomal recessive lysosomal storage disease relatively common in the Finnish population. The main manifestations of more than 70 patients detected to date are severe psychomotor retardation and ataxia of early onset. Intracellular free n-acetylneuraminic acid (sialic acid) is increased 10-20-fold and localized in the lysosomes. Four pregnancies at risk were monitored by quantitation of free and total sialic acid in amniocytes and supernatant amniotic fluid by high-performance liquid chromatography. In 3 children results were normal. Free sialic acid content of the amniocytes from one affected child was 2.6 nmol/mg protein, which was approximately 5 times higher than that of the 3 unaffected children (0.3 to 0.8) and 14 control samples (0.3 to 0.9). The ratio of free/total sialic acid of the amniocytes also clearly distinguished the affected pregnancy (13.8%) from the unaffected (2.3-4.8%) and control individuals (1.8-5.3%). This represents the first successful prenatal identification of a patient with Salla disease and indicates that both free sialic acid and free/total sialic acid ratio should be monitored in pregnancies at risk for the disease.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
4/4. L-2-hydroxyglutaric aciduria: clinical heterogeneity versus biochemical homogeneity in a sibship.Three out of four sibs in a North-African family were affected with L-2-hydroxyglutaric aciduria. The youngest sib was most severely handicapped: she was diagnosed at 2.5 years of age, whereas the then 7- and 10-year-old siblings had a less pronounced psychomotor retardation. All patients had an increased head circumference in contrast to the healthy, non-affected sibling. urine and plasma levels of L-2-hydroxyglutaric acid in the three sibs were similar and showed only a small variation. magnetic resonance imaging (MRI) of the brain in the eldest sib showed hyperintense signal on T2-weighted images of the basal ganglia, dentate nucleus and subcortical white matter. The youngest sib showed identical white matter abnormalities of the corpus medullare cerebelli. These abnormalities were consistent with demyelination and/or spongiosis. On two occasions cerebrospinal fluid amino acid chromatography in the youngest sib showed an increased concentration of lysine and a decreased level of glutamine. Plasma lysine was normal. It is concluded that L-2-hydroxyglutaric aciduria is almost invariably associated with neurological disease; the severity of the symptoms does not seem to be completely dependent on the extent of the biochemical abnormalities and may even be variable within a family.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |