bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of placental enzyme analysis in assessment of the newborn at risk for nonketotic hyperglycinaemia (NKH)
Authors: Toone J. R. , Applegarth D. A. 
Published: June 2005

SummaryThe incidence of non‐ketotic hyperglycinaemia (NKH), McKusick 23830, in the population of British Columbia, Canada was found to be the same as that reported for Finland. We present the plasma glycine levels in ten non‐ketotic hyperglycinaemia patients and outline difficulties in interpreting plasma glycine levels in their newborn siblings. We propose the use of a placental glycine cleavage enzyme (EC 2.1.1.10) assay to rule out a diagnosis of non‐ketotic hyperglycinaemia in at‐risk infants during the first few days of life.
Prenatal diagnosis of 3‐Hydroxy‐3‐methylglutaric aciduria by GC‐MS and enzymology on cultured amniocytes and chorionic villi
Authors: Chalmers R. A. , Tracey B. M. , Mistry J. , Stacey T. E. , McFadyen I. R. 
Published: June 2005

SummaryThis paper reports the prenatal diagnosis of HMG CoA lyase deficiency at 16 weeks' gestation by direct chemical analysis of cell‐free amniotic fluid and by measurement of HMG CoA lyase activity in cultured amniocytes. Termination of an affected fetus allowed study of chorionic villus tissue, the results providing the basis for future first trimester prenatal diagnoses of this condition. An abstract report of this work has appeared elsewhere (Chalmerset al., 1985).
Recent advances in the molecular genetics of the neuronal ceroid lipofuscinoses
Authors: Mole S. E. 
Published: June 2005

SummaryMajor advances in the molecular genetic analysis of the neuronal ceroid lipofuscinoses (NCL) have recently been made: the genes for two major types have been identified and the chromosomal location for a third defined.CLN1, the gene for infantile NCL (Santavuori‐Haltia disease) encodes palmitoyl protein thioesterase (PPT). Most patients (75% of disease chromosomes) have the same point mutation. In contrast,CLN3, the gene for juvenile NCL (Batten or Spielmeyer‐Vogt‐Sjögren disease) is not a previously known gene, nor does its product display homology to any previously described proteins. The same 1 kb genomic deletion is present in the majority of patients (81% of disease chromosomes).CLN5, the gene for Finnish variant late infantile NCL, has been mapped to 13q and should be identified in the near future. The gene for late‐infantile NCL (Jansky‐Bielschowsky disease) has not yet been localized to a chromosome despite intensive research. It is likely that this type of NCL is caused by mutations in more than one gene each resulting in the same phenotype.
A fluorimetric enzyme assay for the diagnosis of sanfilippo disease type A (MPS IIIA)
Authors: Karpova E. A. , Voznyi Ya. V. , Keulemans J. L. M. , Hoogeveen A. T. , Winchester B. , Tsvetkova I. V. , van Diggelen O. P. 
Published: June 2005

Summary4‐Methylumbelliferyl‐α‐d‐N‐sulphoglucosaminide (MU‐α‐GlcNS) was synthesized and shown to be a substrate for the lysosomal heparin sulphamidase. Sanfilippo A patients' fibroblasts (n=42) and lymphocytes (n=1) showed 0–3% of mean normal heparin sulphamidase activity; in total leukocytes from patients (n=8) sulphamidase activity was clearly deficient. In fibroblasts from obligate heterozygotes for Sanfilippo A, the sulphamidase activity was reduced in 9 out of 10 cases. Heparin sulphamidase desulphates MU‐αGlcNS to MU‐αGlcNH2 and further hydrolysis during a second incubation is required to liberate 4‐methylumbelliferone, which can be measured. Yeastα‐glucosidase, which has low but sufficientα‐glucosaminidase activity, was used to hydrolyse the reaction intermediate MU‐αGlcNH2 to release 4‐methylumbelliferone and free glucosamine.
Clinical and molecular heterogeneity of cytochromec oxidase deficiency in the newborn
Authors: Lombes A. , Romero N. B. , Touati G. , Frachon P. , Cheval M. A. , Giraud M. , Simon D. , Ogier de Baulny H. 
Published: June 2005

SummaryWe report 8 cases of severe cytochromec oxidase deficiency with onset in the neonatal period. Clinical symptoms were heterogeneous: antenatal cerebral malformations, neurological distress with ketoacidosis, severe myopathy, or isolated respiratory control failure. Lactic acid was elevated in blood and/or CSF in 7 cases. Muscle biopsy (7 patients), liver biopsy (4 patients), and cultured skin fibroblasts (7 patients) were used to assess the cytochromec oxidase deficiency. Among the patients, the enzymatic defect differed in the level of residual activity, expression in different tissues and subunit composition in muscle (as analysed by immunohistochemistry). Southern blot analysis of the mitochondrial DNA was normal in 7 patients. The heterogeneity of cytochromec oxidase deficiency was therefore demonstrated by these clinical presentations and by the biochemical assessment of the enzyme defect. This reflects, most probably, the diverse nature of the causal mutations.
Two siblings with episodic ketoacidosis and decreased activity of succinyl‐CoA:3‐ketoacid CoA‐transferase in cultured fibroblasts
Authors: Pretorius C. J. , Loy Son G. G. , Bonnici F. , Harley E. H. 
Published: June 2005

SummarySuccinyl‐CoA:3‐ketoacid CoA‐transferase deficiency leads to a severe ketoacidosis presenting in infancy. We describe two siblings of African ancestry who presented with repeated episodes of ketoacidosis. Both had a positive test for salicylate in the absence of salicylate ingestion. Analysis of urine for organic acids revealed the presence of acetoacetate and 3‐hydroxybutyrate. Succinyl‐CoA:3‐ketoacid CoA‐transferase activities in cultured fibroblasts were 11% and 18% of control values.
Metabolic abnormalities in feline Niemann‐Pick type C heterozygotes
Authors: Brown D. E. , Thrall M. A. , Walkley S. U. , Wurzelmann S. , Wenger D. A. , Allison R. W. , Just C. A. 
Published: June 2005

SummaryNiemann‐Pick disease type C (NPC) is an autosomal recessive neurovisceral lysosomal storage disorder in which cholesterol lipidosis results from defective intracellular transport of unesterified cholesterol. The primary molecular defect of NPC is unknown; regulatory mechanisms of cholesterol metabolism are impaired, resulting in retarded esterification of exogenous cholesterol with accumulation of unesterified cholesterol in lysosomes and secondary storage of glycolipids and sphingomyelin. In obligate heterozygotes from a feline NPC model, cultured skin fibroblasts challenged with exogenously derived cholesterol exhibited intermediate rates of cholesterol esterification and accumulation of unesterified cholesterol. Liver lipid analyses of obligate heterozygote cats demonstrated intermediate cholesterol and sphingomyelin concentrations. Vacuolated skin fibroblasts were found in 2 of 3 heterozygote cats, and occasional cortical neurons exhibited intracellular inclusions immunoreactive for GM2‐ganglioside. Ultrastructural studies provided evidence of storage in liver and brain. We believe these morphological and biochemical findings are the first example of manifestations of CNS abnormalities in a genetic carrier for a neuronal storage disease.
Marked increase of methylumbelliferyl‐tetra‐N‐acetylchitotetraoside hydrolase activity in plasma from gaucher disease patients
Authors: den Tandt W. R. , van Hoof F. 
Published: June 2005

SummaryMethylumbelliferyl‐tetra‐N‐acetylchitotetraoside hydrolase activity was increased 53‐ to 484‐fold in plasma from Gaucher disease patients and no activator could be found. High activity was also measured in other lysosomal storage diseases including Krabbe disease, Wolman disease, GM1‐gangliosidosis and to a lesser extent Niemann‐Pick disease type B, but the activities were lower than the lowest values in Gaucher patients.Kinetic properties of the high activity in Gaucher plasma were similar to those of controls. It is not known whether the increased activity represents intrinsic enzyme activity or increased enzyme concentration. It is possible that this enzyme may help in the detection of Gaucher disease or in the assessment of enzyme therapy withβ‐d‐glucosidase (Ceredase®).
Chorionic villus sampling: Diagnostic uses and limitations of enzyme assays
Authors: Fowler B. , Giles L. , Cooper A. , Sardharwalla I. B. 
Published: June 2005

SummaryControl ranges for enzymes in uncultured chorionic villi were established, based on: (1) 21 of 22 enzymes (mainly lysosomal) in villi had similar properties to the enzyme in cultured fibroblasts; (2) isoenzyme patterns in villi were similar to those in fibroblasts for five lysosomal enzymes but different for aryl sulphatases; (3) control ranges were determined for 12 enzymes in abortion villi and for 21 enzymes in biopsy villi, values tending to be higher in the latter for those enzymes studied in both types of sample; (4) storage of samples under various conditions revealed no major changes in activity of seven lysosomal enzymes.A number of potential pitfalls in the use of chorionic villus samples for diagnosis of metabolic disorders by enzyme assay are described: (1) the presence of aryl sulphatase C in chorionic villi, an isoenzyme which may interfere in assays of aryl sulphatase A; (2) the presence of maternal enzyme in chorionic villus material illustrated by the detection of the A isoenzyme of B‐hexosaminidase in chorionic villus from a pregnancy affected with Sandhoff's disease; (3) the finding of falsely normal levels of α‐iduronidase in chorionic villus samples from a pregnancy affected with Hurler's disease, probably due to contamination with maternal tissue which has relatively high levels of this enzyme compared with fetal chorionic material: (4) the inadequacy of indirect assays of incorporation of radiolabel into macromolecules using chorionic villi, for example [14C]propionate incorporation for prenatal diagnosis of methylmalonic aciduria.Provided that such pitfalls are recognized and great care is taken in selection of villus samples and interpretation of results, chorionic villus sampling allows reliable prenatal diagnosis of a large number of disorders using enzyme asays.
Prenatal diagnosis and prevention of inherited abnormalities of collagen
Authors: Pope F. M. , Daw S. C. M. , Narcisi P. , Richards A. R. , Nicholls A. C. 
Published: June 2005

SummaryThere is now strong evidence for the implication of collagen α1(I), α2(I) and α1(III) mutations in many forms of osteogenesis imperfecta and inherited arterial aneurysms (Ehlers Danlos syndrome type IV). A sizeable proportion of these disorders have detectable abnormalities by conventional protein chemistry, immunofluorescence, or more sophisticated DNA analysis. Everyone of them with specific defects or with linkage to appropriate gene markers is therefore amenable to prevention using conventional prenatal diagnosis by chorionic villus biopsy (with fibroblast culture), fetoscopic biopsy (with fibroblast culture), ultrasound diagnosis of the severely deformed fetus, or gene linkage studies by chorionic villus biopsy or amniocentesis.Already many collagen α1(I), α2(I) and α1(III) mutations have been characterized including point mutations, small and large deletions and regulatory mutations. Many others are likely to be rapidly studied by exploiting recent advances in DNA technology, and other strong candidate genes include collagen II (some chondrodystrophies), collagen VI (certain arterial and cardiovascular diseases) and collagen VII (dystrophic epidermolysis bullosa). Other important common diseases are likely to include osteoporosis, osteoarthritis and cerebral aneurysms.A detailed review is provided of collagen interstitial genes and proteins, together with a description of the various forms of osteogenesis imperfecta and Ehlers Danlos syndrome in which either collagen α1(I), α2(I) or α1(III) mutations have been identified. Appropriate restriction length polymorphisms (RFLPs) useful in identifying carriers of these mutant genes are also described.
Prenatal diagnosis of Duchenne muscular dystrophy: A three‐year experience in a rapidly evolving field
Authors: Bakker E. , Bonten E. J. , Veenema H. , den Dunnen J. T. , Grootscholten P. M. , van Ommen G. J. B. , Pearson P. L. 
Published: June 2005

SummaryApplication of molecular genetic techniques has greatly increased diagnostic possibilities of hereditary disorders. In 1983 the first linkage of Duchenne muscular dystrophy with flanking DNA probes was described, which made carrier detection possible in a limited number of cases. The first published prenatal diagnosis for Duchenne muscular dystrophy dates from 1985. DNA‐analysis for Duchenne muscular dystrophy and Becker muscular dystrophy has become increasingly informative, firstly by the development of more flanking markers, followed by intragenic probes detecting deletions and, more recently, by the use of cDNA probes detecting a deletion or duplication mutation in over 60% of the Duchenne and Becker muscular dystrophy patients. Although these developments allow a highly reliable (>99%) carrier detection and prenatal diagnosis in over 90% of cases, the continuing introduction of new probes and/or technologies has necessitated constant reappraisal of many families to derive maximum information. During the past 3 years we applied prenatal diagnosis for Duchenne and Becker muscular dystrophies with DNA‐analysis on 53 male fetuses in 47 families. Twenty‐two healthy male babies were born, after being diagnosed to have a low Duchenne muscular dystrophy risk. Two pregnancies also diagnosed as low risk have not yet come to term. In the other cases a high risk for Duchenne muscular dystrophy was found and the parents chose abortion. Our studies also revealed a number of important diagnostic pitfalls, such as non‐paternity, karyotypic anomalies and gonadal mosaicism.
Gene mapping of mineral metabolic disorders
Authors: Thakker R. V. , Davies K. E. , O'Riordan J. L. H. 
Published: June 2005

SummaryRecent advances in the techniques of molecular biology and cytogenetics have enabled the localization of several mutant genes which result in disorders of phosphate, calcium, magnesium and water homeostasis. Thus, the genes causing X‐linked hypophosphataemic rickets, Lowe's syndrome, Di George syndrome, X‐linked recessive hypoparathyroidism, multiple endocrine neoplasia Type I, primary hypomagnesaemia and X‐linked nephrogenic diabetes insipidus have been mapped. The molecular and genetic studies which localized these disease genes are described and the implications of this gene mapping in genetic counselling and in further elucidation of the mineral metabolic defects are discussed.
A new case of dihydropyrimidine dehydrogenase deficiency
Authors: Brockstedt M. , Jakobs C. , Smit L. M. E. , van Gennip A. H. , Berger R. 
Published: June 2005

SummaryWe present the clinical and biochemical features of a boy with dihydropyrimidine dehydrogenase deficiency, which seem to underline a disease entity of developmental retardation, epilepsy and muscular hypertonia.
PAH deficiency in Italy: correlation of genotype with phenotype in the Sicilian population
Authors: Romano V. , Guldberg P. , Güttler F. , Meli C. , Mollica F. , Pavone L. , Giovannini M. , Riva E. , Biasucci G. , Luotti D. , Palillo L. , Calí F. , Ceratto N. , Anello G. , Bosco P. 
Published: June 2005

SummaryThe results of the neonatal screening for phenylalanine hydroxylase (PAH) deficiency in Sicily show that its incidence is higher than previously reported for mainland Italians and that non‐PKU HPA is in excess of classical and mild PKU. The latter finding suggests that a high number of non‐PKU HPA mutations would occur in the Sicilian population compared to populations with an inverted PKU/non‐PKU HPA ratio. Previous studies have identified 40 mutations accounting for the majority (98%) of mutant alleles underlying PAH deficiency in Sicily. In order to study the molecular basis of the distribution of PAH deficiency phenotypes in the Sicilian population, we have correlated 31 of those mutations with clinical and metabolic phenotypes in 12 mentally retarded patients, 14 treated patients with classic or mild PKU, and 13 subjects presenting the non‐PKU HPA phenotype. The present study proposes a tentative classification for a large number (26) of PAH gene mutations which may represent an additional tool for establishing a differential diagnosis for PAH deficiency in the Sicilian population.
Congenital non‐progressive encephalopathy and deafness with intermittent episodes of coma and hyperkynureninuria
Authors: Cheminal R. , Echenne B. , Bellet H. , Duran M. 
Published: June 2005

SummarySix of nine children born from first‐cousin parents presented with the same clinical picture: non‐progressive congenital encephalopathy with marked hypertonia resembling the stiff‐baby syndrome, delayed milestones, mental deficiency and congenital deafness. Rare, usually reversible, episodes of sudden worsening of the neurological status, with progressive loss of consciousness and increase of hypertonia, occurred spontaneously or during febrile illnesses. During these periods, and sometimes on other occasions, transitory renal dysfunction was observed (nephrotic syndrome and/or tubular abnormalities). Death occurred before age 2 years in 4 patients; 2 are still alive (10 and 13 years old). Electrophysiological, biological and enzymatic investigations remained negative, particularly those concerning mitochondrial and peroxisomal metabolism. The only biochemical anomaly was a massive hyperkynureninuria, seen only during the periods of coma (up to 213 µmol/mmol creatinine; normal < 10) and after an intravenous protein loading test. This suggests an anomaly of tryptophan metabolism which has not been reported up to now.
Clinical polymorphism of cystinosis encephalopathy. Results of treatment with cysteamine
Authors: Broyer M. , Tête M. J. , Guest G. , Berthélémé J. P. , Labrousse F. , Poisson M. 
Published: June 2005

SummaryOf the 26 cystinotic patients over 19 years of age followed in our institution, 7 developed CNS complications at a mean age of 23 years. Two forms were observed. The first, associating cerebellar and pyramidal signs, mental deterioration and finally pseudo‐bulbar palsy, may be called cystinosis encephalopathy. The other form resembled a stroke‐like episode with coma and hemiplegia or milder symptoms. Hydrocephalus was rare and not associated with clinical symptoms in this series. Cysteamine was administered for longer than 6 months to 4 of the patients with encephalopathy. Two had an almost complete disappearance of their symptoms including the gross abnormalities of MR imaging in one; one improved partially and remained stable, and one continued to deteriorate but was suspected of noncompliance. These results suggest that cysteamine may be an effective treatment of cystinosis encephalopathy and encourage prescription of this drug in cystinosis in order to prevent this complication
Colorimetric determination of sulphatide in cultured fibroblasts from patients with various types of metachromatic leukodystrophy after sulphatide loading test
Authors: Wiesmann U. N. , Burkhart T. , von Känel J. , Toennesen T. , Ghidoni R. 
Published: June 2005

ConclusionIntracellular determination of sulphatide by the two methods gave very good correlation. The detection limit for the colorimetric methods was in the low nanomolar range per mg protein, providing enough specificity and sensitivity for the determination of sulphatide in fibroblasts after a loading test. While the determination of radiolabelled 3‐OH‐sulphatide is quite time‐consuming and requires special techniques, the colorimetric assay is relatively simple and can be performed in any laboratory equipped for biochemical analyses. The colorimetric test can be used to develop more sensitive sulphatide loading tests which will be better able to discriminate between the various forms of typical and atypical MLD.
Maternal phenylketonuria pregnancy outcome: a preliminary report of facial dysmorphology and major malformations
Authors: Rouse B. , Lockhart L. , Matalon R. , Azen C. , Koch R. , Hanley W. , Levy H. , dela Cruz F. , Friedman E. 
Published: June 2005

ConclusionIt is clear from the preliminary data that major malformations, i.e. intrauterine growth retardation, microcephaly and cardiac defects, tend to decrease in frequency as the blood phenylalanine level drops, but not enough to suggest that phenylalanine levels of 600µmol/L are safe levels. The facial dysmorphic features may be used as a sensitive indicator that blood phenylalanine levels should be below 360µmol/L. It is hoped that at the end of the collaborative study more data will be available to suggest blood phenylalanine levels which will prevent the deleterious effects of maternal PKU syndrome.
X‐linked cardioskeletal myopathy and neutropenia (Barth syndrome): Respiratory‐chain abnormalities in cultured fibroblasts
Authors: Barth P. G. , Van den Bogert C. , Bolhuis P. A. , Scholte H. R. , van Gennip A. H. , Schutgens R. B. H. , Ketel A. G. 
Published: June 2005

ConclusionsThe ATP production from glutamate + malate, pyruvate + malate, or succinate (+ rotenone was lower than the mean values found in control fibroblasts in patient 1 and in the low‐normal range in patient 2. Decreased activities of complex III (±30% of controls) and complex IV (±60% of controls) are in agreement with the previous studies in muscle. These findings provide evidence that respiratory‐chain dysfunction is an essential component of Barth syndrome. Results further indicate that the gene product is essential for the function, formation or stability of both complex III and complex IV. Both complex III and complex IV contain subunits that are encoded by mtDNA. The results of emetine labelling make it unlikely that the gene is involved in the expression of mtDNA. We furthermore suspect that 3‐methylglutaconic aciduria in this syndrome represents an epiphenomenon which is as yet unexplained but has been described so far in patients with separate mitochondrial disorders (Gibson et al 1995).
The mutational spectrum in very long‐chain acyl‐CoA dehydrogenase deficiency
Authors: Andresen B. S. , Vianey‐Saban C. , Bross P. , Divry P. , Roe C. R. , Nada M. A. , Knudsen I. , Gregersen N. 
Published: June 2005

ConclusionWe have shown that all of seven unrelated patients with defective palmitoyl‐CoA dehydrogenation have mutations in VLCAD, indicating that they suffer from VLCAD deficiency.Our study illustrations that there is a large mutational heterogeneity in VLCAD deficiency. It is not at present possible to judge whether or to what extent this large mutational heterogeneity may explain the varying clinical picture observed in this disease.
Improved selectivity of urinary oligosaccharide screening using two one‐dimensional TLC systems
Authors: Abeling N. G. G. M. , Rusch H. , van Gennip A. H. 
Published: June 2005

ConclusionsCombination of two one‐dimensional TLC systems provides additional discriminative power with respect to pathology. Breast‐feeding patterns can be distinguished from the α‐mannosidase patterns in the new TLC system using isopropanol.We prefer the combination of the regular system with the isopropanol system.