1/10. fucosidosis: a neuropathological study.The involvement of the central nervous system in fucosidosis is related to severe lesions of both nerve and glial cells. The morphology of cells degeneration is characterized by both vacuoli containing water-soluble fuco-derivatives (fuco-oligosaccharides) and/or granular substances probably constituted by fuco-sphingolipds. The cerebral cortex is the most severely affected. The involvement of the white matter is related to the glial cells degeneration. The relationship between the morphology of nerve and glial cells lesions, and the accumulation of oligosaccharides and sphingolipids following the absence of alpha-l-fucosidase, is briefly discussed.- - - - - - - - - - ranking = 1keywords = white (Clic here for more details about this article) |
2/10. Pontocerebellar hypoplasia associated with respiratory-chain defects.Pontocerebellar hypoplasias are congenital disorders of brain morphogenesis which include such diverse etiologies as carbohydrate-deficient glycoprotein syndrome type 1, cerebromuscular dystrophies (walker-warburg syndrome, Fukuyama syndrome, muscle-eye-brain disease) and at least two types of autosomal recessive neurodegenerations known as pontocerebellar hypoplasia type I and II. Pontocerebellar hypoplasia type 1 is a lethal phenotype and clinical features include congenital contractures, respiratory insufficiency, central and peripheral motor dysfunction and spinal anterior horn degeneration. Type 2 is characterized by progressive microcephaly, extrapyramidal dyskinesia and normal spinal cord findings. In this paper, we describe a girl, born at 33 weeks of gestation, presenting with respiratory insufficiency and multiple contractures. MRI scan of the brain demonstrated pontocerebellar hypoplasia and cortical and diffuse periventricular white matter abnormalities. Postmortem examination showed pontocerebellar hypoplasia with extensive gliosis of the periventricular white matter and of the basal ganglia with normal spinal cord findings. histology of skeletal muscle was normal. Biochemical analysis demonstrated multiple deficiencies of respiratory chain enzymes in skin fibroblasts. This case demonstrates a lethal phenotype of pontocerebellar hypoplasia without spinal cord abnormalities associated with a respiratory-chain disorder. The diagnostic workup in a patient whose brain image shows pontocerebellar hypoplasia should include a search for respiratory-chain impairment.- - - - - - - - - - ranking = 2keywords = white (Clic here for more details about this article) |
3/10. Leukoencephalopathy associated with a disturbance in the metabolism of polyols.In vivo proton magnetic resonance spectroscopy of the brain demonstrated highly elevated levels of arabitol and ribitol in a 14-year-old boy with a white matter disorder and neuropathy of unknown origin. These polyols also were shown to be elevated in body fluids, suggesting an inborn error in polyol metabolism. The strong plasma/ cerebrospinal fluid/brain gradient, with concentrations increasing in that order, suggests a primary neurometabolic disorder. Thus far, a basic enzyme defect has not been identified.- - - - - - - - - - ranking = 1keywords = white (Clic here for more details about this article) |
4/10. glucose-phosphate isomerase deficiency due to a new variant (GP I Barcelona) and to a silent gene: biochemical, immunological and genetic studies.A 12-year-old girl of Spanish origin was found to be double heterozygote for a deficient GP I variant (GP I Barcelona) and for a silent GP I gene. The mother was heterozygote for GP I Barcelona and the father was heterozygote for the silent gene. GP I Barcelona was a fast variant (116%) with an increased isoelectric point (9.55), lability to heat and to urea, and shift of the pH curve towards the acidic pH. The other kinetic characteristics were normal. The ratio of enzymatic activity to immunological reactivity was normal in erythrocytes and white blood cells of the father and the mother but decreased to 75% of normal in blood cells of the daughter. The genetic and molecular mechanisms of GP I deficiency of this patient are discussed.- - - - - - - - - - ranking = 11.367188830742keywords = blood cell, white (Clic here for more details about this article) |
5/10. High myopia and congenital myopathy with partial pachygyria in cutis laxa syndrome.PURPOSE: Several types of inborn errors of the O-glycan biosynthesis are known, leading to clinically very distinct phenotypes. Children with O-mannosyl glycan biosynthesis defects commonly present as a severe form of congenital muscular dystrophy with decreased alpha-dystroglycan staining, congenital eye anomalies, and brain migration defects. Alpha-dystroglycan is an O-mannosylated glycoprotein with additional mucin type O-glycans. methods: Based on overlapping clinical features with O-mannosyl glycan defects, especially with muscle-eye-brain disease, the authors performed a muscle biopsy in a child with severe congenital hypotonia, high myopia, partial pachygyria, mental retardation, cutis laxa, and an inborn error affecting the biosynthesis of both mucin type O-glycans and N-linked glycans. RESULTS: The histology showed no signs of muscle dystrophy, but a mild myopathy with slight increase in the muscle fiber diameter variability and type I fiber predominance. No significant decrease in the alpha-dystroglycan staining was detected; therefore, in spite of the phenotypic similarities the authors could not confirm the role of abnormal dystroglycan in the etiology of the muscle weakness and the developmental anomalies. CONCLUSIONS: High myopia, muscle weakness, and cortical neuronal migration abnormalities are common in disorders of O-mannosylation and also observed in the authors' patient. However, compared to the severe generalized defect observed in mannosyl glycan defects, in this child the cerebral white matter and cerebellum were spared, and no muscle dystrophy could be confirmed. This is the first description of high myopia in cutis laxa syndrome in combination with congenital disorders of glycosylation.- - - - - - - - - - ranking = 1keywords = white (Clic here for more details about this article) |
6/10. Neuropathology of Salla disease.A neuropathological study was performed on two patients with Salla disease, one male and one female, from different families. They both died at the age of 41 years. Both patients showed increased excretion of free sialic acid in the urine, psychomotor retardation starting in the 1st year of life, ataxia and spasticity. Several family members of both families were affected with the same disease indicating the hereditary character of the disorder. The neuropathological investigation revealed strikingly similar changes in the two cases. Macroscopically the cerebral white matter was severely reduced. Histologically marked loss of axons and myelin sheaths was accompanied by pronounced astrocytic proliferation. The remaining axons frequently showed ovoid swellings surrounded by a myelin sheath. The reduction of the number of myelin sheaths seemed proportional to the numerical reduction of axons. Many cortical nerve cells displayed in relation to age an abnormal amount of lipofuscin. neurofibrillary tangles were observed in nerve cells of the neo-cortex, nucleus basalis of Meynert and locus ceruleus. cerebellum showed moderate loss of purkinje cells. In the spinal cord axonal degeneration was observed in both ascending and descending tracts.- - - - - - - - - - ranking = 1keywords = white (Clic here for more details about this article) |
7/10. Antenatal diagnosis in three pregnancies at risk for mannosidosis.Three pregnancies were monitored in two families at risk for mannosidosis, alpha mannosidase and alpha fucosidase were determined on extracts from white blood cells of several members of these families, on fibroblast cell lines from the index cases and on uncultured and cultured amniotic cells of the foetuses. Two foetuses were diagnosed as affected and one as being free from the disease. The conclusions were confirmed on the affected foetuses after interruption of the pregnancy. The noticeable residual activity of alpha mannosidase found in some fibroblasts and cultured amniotic cells required complementary investigations (heat lability and dependency of substrate concentration) to reach a reliable diagnosis. Invesitgation of uncultured amniotic cells may give useful additional information.- - - - - - - - - - ranking = 6.1835944153711keywords = blood cell, white (Clic here for more details about this article) |
8/10. Familial fanconi syndrome with malabsorption and galactose intolerance, normal kinase and transferase activity. A report on two siblings.Two siblings of Turkish-Assyrian extraction, whose parents were first cousins, had poor appetite, slow weight gain and retarded psychomotor development. When given milk the galactose concentration in blood increased. An oral galactose load showed a markedly reduced capacity to metabolize galactose. fanconi syndrome was present as in classical galactosemia. A galactose-free diet reduced the aminoaciduria but did not normalize the renal tubular function nor the children's general condition. galactokinase and galactose-1-phosphate uridyltransferase activities in red blood cells were normal. The physical appearance of the children (sparse subcutaneous fat, thin extremities and distended abdomen) and the results of vitamin a and xylose absorption tests, were in accordance with a malabsorption condition. glucose, however, seemed to be absorbed normally from the gut. There was no evidence of primary liver disease. Since the condition did not normalize with a galactose-free diet, an enzyme defect of galactose metabolism is unlikely. Instead, a more general transport defect with autosomal recessive inheritance is proposed.- - - - - - - - - - ranking = 5.1835944153711keywords = blood cell (Clic here for more details about this article) |
9/10. '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 = 6.1835944153711keywords = blood cell, white (Clic here for more details about this article) |
10/10. uridine diphosphate galactose 4-epimerase deficiency.A case of uridine diphosphate galactose (UDP-Gal) 4-epimerase deficiency was discovered by mass screening of newborn infants. UDP-Gal 4-epimerase activity of red blood cells from the patient was found to be remarkably low, i.e., 7.5% of the level in normal controls at comparable ages. The parents showed intermediate values between those of the patient and controls. The enzyme activity in a specimen of liver tissue obtained from the patient by needle biopsy revealed a normal value. Subsequently, two other families with the condition were found by mass screening and these individuals were found to be heterozygotes.- - - - - - - - - - ranking = 5.1835944153711keywords = blood cell (Clic here for more details about this article) |
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