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J Zeman

Publications and source records attributed to J Zeman.

141 records · Page 8Linked to original sources
PubMedDate not supplied

An atypical ultrastructural pattern in Fabry's disease: a study on its nature and incidence in 7 cases.

This is a report on a stored lipid atypical ultrastructural pattern in skin samples of Fabry's disease expressed exclusively in the endothelium. The pattern consisted of intersecting short crescentic tightly packed membranes with a periodicity identical to that in classical ultrastructural variants. At low magnification the lysosomal aggregates of the material resembled "sunbursts" or aggregates of densely packed squirming villus-like structures. According to results of ultrastructural, lipid, and lectin histochemical analyses including analysis of the patients' blood groups, it could be concluded that it is just a variant physical state of the otherwise typical Fabry lipid. Its origin could be attributed to impeded formation (or maintenance) of larger lipid lamellae. It was found in great amounts in skin capillaries in 2 cases, and rarely in 5 additional cases. Knowledge of this atypical ultrastructural pattern is of practical significance because it could, if prevalent, cause diagnostic problems.

Adolescent↗
PubMedDate not supplied

Novel mutations in a boy with dihydrolipoamide dehydrogenase deficiency.

BACKGROUND: Dihydrolipoamide dehydrogenase (DLD) deficiency is a rare cause of primary lactic acidosis in infancy. MATERIAL AND METHODS: This article presents the results of biochemical and molecular analyses and metabolic response to treatment procedures in a 10-week old boy presenting with vomiting, progressive hypotonia, lactic acidosis (pH 7.04; BE - 20; B-lactate 6.6 mmol/l, controls <2.1; CSF-lactate 4.8 mmol/l, controls <2.0), increased levels of branched chain amino acids in blood, and increased urinary excretion of branched chain oxo-acids due to DLD deficiency. RESULTS: DLD activity was less than 5% of control values in lymphocytes, muscle mitochondria and fibroblasts. Western blot analysis in muscle tissue showed a decrease in the quantity of DLD protein to 40% in comparison to control. A high-fat, low-protein diet supplemented with MCT oils and sodium dichloroacetate resulted in normalization of lactate, amino acids and organic acids in body fluids, but there was no improvement in psychomotor development. Novel heterozygous mutations were found in the DLD gene: A1081G and G1123A. Both mutations affect the same region of the binding site for FAD. The G1123A mutation, resulting in the substitution of Glu 375 > Lys, breaks down the possible interaction of glutamic acid with neighboring lysine and causes electrostatic and steric repulsion, which is likely to destabilize structure in this part of the protein. In case of the A1081G mutation, resulting in substitution of Met 361 > Val, no important intermolecular interactions are broken and the reason for destabilization of the protein is not as clear. CONCLUSIONS: The prognosis for children with DLD deficiency is unfavorable, although long-term normalization of most metabolites in body fluids may be achieved with the proper diet and the administration of sodium dichloroacetate.

Acidosis, Lactic↗