31/64. fucosidosis.Disseminated angiokeratomas can be seen in patients with an inherited deficiency of alpha-l-fucosidase as well as in patients with classic Fabry's disease. patients with deficiency of this lysosomal enzyme, or fucosidosis, have spasticity, mental retardation, and retardation of growth in addition to angiokeratomas. We herein report three new cases of this rare syndrome.- - - - - - - - - - ranking = 1keywords = deficiency (Clic here for more details about this article) |
32/64. The clinical and biochemical implications of pyruvate carboxylase deficiency.A 10 month old female infant was evaluated for severe lactic acidosis. Clinically she was well nourished and had a substantial amount of adipose tissue despite recurrent episodes of acidosis. Her psychomotor development was retarded, her movements were dystonic and generalized seizures punctuated her course. Metabolic abnormalities included elevated blood concentrations of lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, alanine, proline and glycine, decreased blood concentrations of glutamine, aspartate, valine and citrate, and intermittent elevations of serum cholesterol. A trial on a high-fat diet worsened the clinical condition and intensified the ketoacidosis and hyperalaninemia. Analysis of hepatic tissue obtained by open biopsy revealed increased concentrations of lactate, alanine, acetyl-CoA and other short-chain acyl-CoA esters, and decreased concentrations of oxaloacetate, citrate, alpha-ketoglutarate, malate and aspartate. The blood and tissue metabolic perturbations reflected a deficiency of hepatic pyruvate carboxylase. The apparent Km of hepatic citrate synthase for oxaloacetate was 4.6 micrometer. Calculated tissue oxaloacetate concentrations were 0.50--0.84 micrometer suggesting that tricarboxylic acid cycle activity was severely limited by the decreased availability of this substrate. An iv glucose tolerance test resulted in the paradoxical synthesis of ketone bodies. This observation, coupled with the intermittent hypercholesterolemia and the increased tissue acetyl-CoA concentrations, suggests that pyruvate carboxylase is important in modulating the fractional distribution of intracellular acetyl-CoA between the tricarboxylic acid cycle, the beta-hydroxy-beta-methyl-glutaryl-CoA cycle (and the synthesis of cholesterol and ketone bodies), and fatty acid synthesis. Treatment in future cases might be directed toward increasing tissue concentrations of oxaloacetate.- - - - - - - - - - ranking = 111.4199338711keywords = carboxylase deficiency, carboxylase, deficiency (Clic here for more details about this article) |
33/64. erythrocyte membrane proteins in hereditary glucosephosphate isomerase deficiency.erythrocytes (approximately equal to 50% reticulocytes) obtained from a splenectomized patient with a thermolabile variant of glucosephosphate isomerase (GPI) deficiency showed a striking degree of crenation and decreased filterability through 3-micrometer Nuclepore filters (Nuclepore Corp., Pleasanton, Calif.). membranes prepared by hypotonic lysis of such erythrocytes were found to contain a high molecular weight aggregate which was probably disulphide-bonded. The 10% most dense erythrocyte fraction showed an accentuation of aggregate formation while aggregates could not be detected in the 10% least dense erythrocyte fraction. The aggregate consisted mainly of spectrin (band 1) and a protein with the mobility of 4.2. "Extractability" of spectrin from these membranes was also markedly diminished. Incubation of the erythrocytes for 24 h in substrate-free medium caused more pronounced spectrin aggregation than in low or high reticulocyte controls. Incubation of low or high reticulocyte controls for 24 h in medium that contained glucose completely prevented the formation of the high molecular weight aggregate. GPI-deficient erythrocytes incubated with glucose in the medium showed an accentuation of membrane protein aggregate formation; however, this was almost completely reversed by the addition of adenine and inosine to the incubation medium or by the use of fructose, the intermediate just distal to the "block" in glycolysis, as the sole substrate. ATP and reduced glutathione levels in the GPI-deficient erythrocytes incubated with glucose were similar to that found in the low and high reticulocyte controls. Our findings suggest that only a proportion of erythrocytes (the older, more dense population of cells) are susceptible to the formation of disulphide-bonded aggregates, and that this is directly related to an impairment of substrate flow through the glycolytic sequence. The exact mechanism of aggregate formation in these erythrocytes remains to be elucidated.- - - - - - - - - - ranking = 2.5keywords = deficiency (Clic here for more details about this article) |
34/64. Isolated acid neuraminidase deficiency: a distinct lysosomal storage disease.An 8-month-old female presented with coarse facies and hepatosplenomegaly at birth. growth proceeded at an accelerated rate and mental development was normal. A pattern of dysostosis multiplex developed radiographically. Cytoplasmic inclusions consistent with lysosomal storage disease were demonstrated by electron microscopy in bone marrow, liver, and cartilage cells and in cultured skin fibroblasts. Assays of the fibroblasts revealed a specific deficiency of acid neuraminidase and 6-fold increase in intracellular bound sialic acid. An unidentified macromolecular compound rich in sialic acid was excreted in excessive amounts in the urine. The phenotype suggests defective degradation primarily of glycoproteins and possibly to a lesser extent of keratan sulfate and gangliosides.- - - - - - - - - - ranking = 2.5keywords = deficiency (Clic here for more details about this article) |
35/64. hair changes due to zinc deficiency in a case of sucrose malabsorption.A 7-year-old girl suffering from chronic diarrhoea due to sucrase deficiency was referred because of poor hair growth. Her scalp hair had a poor, colourless appearance and was much thinned in the occipital region. Her skin was dry, but otherwise normal. P-zinc was low (7.9 mumol/l), whereas P-albumin was normal. Oral zinc therapy, 40 mg daily, had a marked beneficial effect on her scalp hair, eyebrows and eyelashes, which became thicker and pigmented. Beau lines appeared on thumb-nails and 4th left finger-nail. A rise in P-zinc and S-alkaline phosphatase levels was observed during the zinc supplementation. Microscopic examination of her poor scalp hair, using polarized light, revealed well-defined abnormalities of the hair shafts, as reported by others in a case of acrodermatitis enteropathica: 1) a marked individual variation in diameter, 2) narrowing often associated with waving or sharp bending and broken ends, 3) striation with a tendency to trichonodosis. Such changes were absent in the pigmented hair appearing after the start of zinc therapy.- - - - - - - - - - ranking = 2.5keywords = deficiency (Clic here for more details about this article) |
36/64. Dyggve-Melchior-Clausen syndrome: normal degradation of proteodermatan sulfate, proteokeratan sulfate and heparan sulfate.It had been suggested that Dyggve-Melchior-Clausen syndrome may be due to the deficiency of a specific sulfatase and/or a protease involved in proteoglycan degradation. The ability of Dyggve-Melchior-Clausen fibroblasts to endocytose and degrade 3H-leucine- and 35S-sulfate-labelled proteodermatan sulfate and 35S-sulfate-labelled proteokeratan sulfate, respectively, was therefore investigated. The turnover of cell-associated 35S-sulfate-labelled heparan sulfate was also followed. In all these experiments Dyggve-Melchior-Clausen fibroblasts behaved normally.- - - - - - - - - - ranking = 0.5keywords = deficiency (Clic here for more details about this article) |
37/64. galactose-1-phosphate accumulation by a Duarte-transferase deficiency double heterozygote.An infant, suspected of having galactosemia following a positive screening test on dried blood spots, was shown to be a Duarte-transferase deficiency compound heterozygote through studies of electrophoretic mobility of the transferase enzyme in blood from the patient and family members. No rise in blood glucose was seen following oral ingestion of galactose. At the same time, galactose rose in plasma and was excreted in the urine; galactose-1-phosphate accumulated in erythrocytes. A galactose-free diet was considered the prudent course in the presence of the patient's inability to metabolize galactose completely.- - - - - - - - - - ranking = 2.5keywords = deficiency (Clic here for more details about this article) |
38/64. 'Pseudohypertriglyceridemia' caused by hyperglycerolemia due to congenital enzyme deficiency.A 76-year-old man was found to have a false hypertriglyceridemia due to a 40-fold increased glycerolemia. This metabolic change was due to a deficiency in glycerol kinase (ATP:glycerol phosphotransferase, EC 2.7.1.30) activity in the cells of this patient as shown by incubation of his white blood cells with [14 C]glycerol. Several chromatographic analyses and quantitative assays were performed on plasma and urine of this patient and of his relatives. The small number of this family's members did not allow to specify the mode of transmission of this genetic trait.- - - - - - - - - - ranking = 2.5keywords = deficiency (Clic here for more details about this article) |
39/64. Lysosomal sialidase deficiency in sialidosis with partial beta-galactosidase deficiency.We analyzed the subcellular localization of sialidases in human lymphocytes from a patient with adult type sialidosis with partial beta-galactosidase deficiency and normal controls. Sialidase activities were measured with alpha,2 leads to 3 NeuAc-lactitol, 4-methylumbelliferyl-NeuAc and GM3 ganglioside as substrates. Sialidases in the lysosomes were sonication-labile and hydrolyzed mainly hydrophilic substrates such as NeuAc-lactitol and 4-methylumbelliferyl-NeuAc, but hydrolyzed subsidiarily GM3 ganglioside. On the other hand, sialidases in the plasma membrane were sonication-stable and hydrolyzed both hydrophilic substrates and GM3 ganglioside. In sialidosis with partial beta-galactosidase deficiency, the sialidases of the lysosomes showed 3-5% activity toward hydrophilic substrates and 25% activity toward GM3 ganglioside as compared with sialidase activities of the controls. However, there are no differences in the activities of the sialidases in the plasma membrane. These results demonstrate that the essential defect in this disease is the deficiency of a lysosomal sialidase.- - - - - - - - - - ranking = 5.5keywords = deficiency (Clic here for more details about this article) |
40/64. Demyelination and disturbed metabolism of pyruvate: a case report.A patient with demyelination is described. Lactate levels were elevated in serum, urine, and cerebrospinal fluid. A decreased pyruvate oxidation rate due to a pyruvate dehydrogenase complex deficiency was demonstrated in muscle and cultured fibroblasts. In muscle mitochondria no structural abnormalities were seen. The clinical course was progressive and the patient died at the age of 6 months.- - - - - - - - - - ranking = 0.5keywords = deficiency (Clic here for more details about this article) |
| <- Previous || Next -> |