bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative use of glucose and fructose in cultured fibroblasts from patients with hereditary fructose intolerance
Authors: Lemonnier F. , Delhotal‐Landes B. , Couturier M. , Decimo D. , Odiévre M. , Gautier M. , Lemonnier A. 
Published: June 2005

AbstractThe utilization of fructose and glucose by fibroblast cultures obtained from patients with hereditary fructose intolerance (HFI) was studied in comparison with fibroblast controls. The cell growth, the time course ofd‐glucose ord‐fructose uptake and the consumption of fructose were similar for both HFI and control cells. Some results showed significant differences between these two cell types: HFI cells consumed less glucose, produced less lactate and contained less glycogen than control cells. Furthermore, significantly less [U‐14C]d‐glucose and [U‐14C]d‐fructose was incorporated into lipids in HFI cells than in control cells. The mechanisms responsible for these differences observed between the two cell types are not known.
The long‐term outcome of patients with glycogen storage diseases
Authors: Smit G. P. A. , Fernandes J. , Leonard J. V. , Matthews E. E. , Moses S. W. , Odievre M. , Ullrich K. 
Published: June 2005

SummaryIn this retrospective study from five centres, 139 patients over 10 years of age with glycogen storage disease types I, III, VI and IX are described. Almost half of the patients with glycogen storage disease type Ia had retarded growth and most had hyperlipidaemia. One‐third of the patients had adenomas, although none of these showed malignant transformations. With increasing age the growth, liver size and hyperlipidaemia of patients with glycogen storage disease type III improve. However, there was a high incidence of myopathy and cardiomyopathy. Patients with glycogen storage disease types VI and IX had a normal growth pattern after childhood. Hepatomegaly and hyperchole‐sterolaemia, however, were still present in half of the patients.
Muscle glycogenosis
Authors: Moses S. W. 
Published: June 2005

SummaryThis review describes clinical, biochemical and genetic features of the four inborn errors affecting muscle glycogen breakdown, namely deficiencies of phosphorylase, phosphorylase kinase, amylo‐1,6‐glucosidase and acid α‐glucosidase. They are characterized by a wide spectrum of clinical manifestation, affecting age of onset, clinical features, progress of disease and tissue involvement. Biochemically, variability of all four enzyme deficiencies is evident in terms of differences in residual enzyme present in tissues, and in the presence or absence of enzyme protein. Genetic heterogeneity, which has been documented in each of the enzyme deficiencies, manifests itself in terms of the presence, absence, quantity or size of mRNA. In phosphorylase deficiency heterogeneity has also been documented at the DNA level. In acid maltase deficiency nine mutant phenotypes have been described affecting various stages of lysosomal enzyme processing.
Inherited disorders of carbohydrate metabolism in children studied by13C‐labelled precursors, NMR and GC‐MS
Authors: Lapidot A. 
Published: June 2005

SummaryGlucose carbon recycling, glucose production and glucose turnover in glycogen storage disease type I and type II patients and control subjects were determined by a novel approach — mass isotopomer analysis of plasma13C glucose. Changes in the isotopomer distribution of plasma13C glucose were found only in glycogen storage disease type III patients and control subjects. Glucose carbon recyling parameters were also derived from13C NMR spectra of plasma glucose C‐1 splitting pattern. Our results eliminate a mechanism for glucose production in glycogen storage disease type I children involving gluconeogenesis. However, glucose release by amylo‐1,6‐glucosidase activity is in agreement with our results.A quantitative determination of the metabolic pathways of fructose conversion to glucose in normal children, and in children with disorders of fructose metabolism was derived from13C NMR measurement of plasma13C glucose isotopomer populations following [U‐13C]fructose administration. A direct pathway from fructose, bypassing fructose‐1‐phosphate aldolase, to fructose‐1,6‐diphosphate in controls and hereditary fructose intolerant children (47% and 27%, respectively) was identified. In children with fructose‐1,6‐diphosphatase deficiency, only the gluconeogenic substrates were13C labelled but no synthesis of glucose from [U‐13C]fructose occurred. The significantly lower (by 68%) conversion of fructose to glucose in hereditary fructose intolerance, as compared to control subjects, and non‐conversion in fructose‐1,6‐diphosphatase deficient subjects after [U‐13C]fructose (∼ 20 mg/kg) administration can serve as the basis of a safe diagnostic test for patients suspected of inborn errors of fructose metabolism and other defects involving gluconeogenesis.
Displacement bone marrow transplantation for some inborn errors
Authors: Hobbs J. R. 
Published: June 2005

SummaryThe initial simple bone marrow transplants for genetic immunodeficiency diseases could hardly be rejected by the host, but required matched sibling donors, only available for about 1 in 5 patients. Improved inductions enabled alternative donors from the family or unrelated volunteers to be used. Measurement of the extent of engraftment by donor cell markers or their normal enzymes showed the need for displacement, which aims to obtain 100% donor‐type marrow so that the future immune responses of the recipient become those of the donor and tolerant to donor cells or their products. Immunoprophylaxis can prevent residual host immune cells from surviving to impair the graft. The concept of DBMT with immunoprophylaxis has evolved either to replace abnormal host cells or to confer a component transferable from donor cells to deficient host tissues. Within 10 years over 40 previously fatal genetic diseases have been satisfactorily corrected and seven partially corrected, but for five there has been inadequate delivery of component to genetically defective tissues such as heart, cartilage and brain. The principles can be applied to some 40 other genetic diseases for which no suitable alternative treatments yet exist.
Transport of amino acids by the human placenta: Predicted effects thereon of maternal hyperphenylalaninaemia
Authors: Kudo Y. , Boyd C. A. R. 
Published: June 2005

SummaryBrush border and basal plasma membrane vesicles prepared from normal term human placental syncytiotrophoblast have been used to study amino acid transport. Such studies are reviewed and novel results presented which confirm that saturation of placental transport by phenylalanine is unlikely to limit delivery of this amino acid to the fetus even with grossly raised maternal concentrations. Such raised maternal levels of phenylalanine are, however, likely to severely embarrass the delivery to the fetus across the placental brush border membrane ofl‐tyrosine and, to a lesser extent, ofl‐tryptophan. Reasons for thinking that this may be relevant to the fetal damage found in maternal PKU are discussed.
Transport of amino acids across the blood‐brain barrier: Implications for treatment of maternal phenylketonuria
Authors: Gardiner R. M. 
Published: June 2005

SummaryAmino acid transport at the mammalian blood‐brain barrier has been extensively characterized. Transport ofl‐phenylalanine and related neutral amino acids is known to be mediated by a stereospecific, sodium independent, saturable carrier. The affinity of this carrier is much higher than that of comparable systems in other tissues. This feature renders it susceptible to inhibition. It has been suggested that inhibition of neutral amino acid influx into the brain by hyperphenylalaninaemia contributes to the pathophysiology of brain damage in this condition.Methods for investigation of amino acid transport at the blood‐brain barrier are discussed, and current knowledge of blood‐brain barrier amino acid transport at the blood‐brain barrier is reviewed. Developmental changes are delineated, with particular reference to recent work on the ovine blood‐brain barrier.There is insufficient information concerning blood‐brain barrier transport of amino acids in the fetal brain to allow firm conclusions to be drawn concerning implications for treatment of maternal PKU. Reasonable extrapolation from animal data suggests that transport inhibition may contribute to impaired fetal brain growth in maternal PKU, and can be minimized by attempts to maintain a normal milieu from the time of conception.
Maternal phenylketonuria — the irish experience
Authors: Naughten E. , Saul I. P. 
Published: June 2005

SummaryThe outcome of 48 pregnancies in 18 women with elevated phenylalanine was studied. The women were divided into two groups, diet and non‐diet. All the women on diet had severe hyperphenylalaninaemia and only six were on the amino acid mixture at conception. In the non‐diet group four women had concentrations of less than 1000 µmol/L and five had severe hyperphenylalaninaemia. Three deaths and one stillbirth occurred in the nondiet group. Microcephaly occurred in 24 children; 11 in the diet group and 13 in the non‐diet group. There were five miscarriages in the non‐diet group and one in the diet group. Diet is beneficial when started early but planned pregnancies, good motivation and compliance were difficult to achieve in this group of women despite every reasonable effort by the PKU clinic.
Cognitive development in offspring of untreated and preconceptionally treated maternal phenylketonuria
Authors: Güttler F. , Lou H. , Andresen J. , Kok K. , Mikkelsen I. , Nielsen K. B. , Nielsen J. B. 
Published: June 2005

SummaryA survey is given of literature reports on the effect of performance in offspring from 26 maternal PKU pregnancies treated prior to conception. The survey includes two women who were referred to us for genetic counselling because they had both given birth to microcephalic, mentally retarded children. The women were discovered to suffer from unrecognized maternal PKU with fasting phenylalanine concentration of 1.1–1.5mmol/L. A strict diet was introduced prior to planned pregnancy and after some months on diet (phenylalanine concentrations <0.6 mmol/L) they became pregant again. Serum phenylalanine levels were monitored weekly throughout pregnancy, and adjustments in the diet were made to keep serum phenylalanine concentration within the range of 0.18–0.42 mmol/L. The outcome of the pregnancies were healthy children who have developed normally. Their IQs are 105 and 119 at ten and four years of age, respectively and their head circumferences are normal. Our data show that the effect of preconceptional dietary treatment was children with a normal performance, contrary to their older siblings born following untreated pregnancies. These results are in agreement with the survey of ten years' promising experiences with preconceptional treatment in maternal PKU. The data may help to motivate young PKU women to accept planned pregnancies and to encourage them to return to the strict diet, which has prevented them from being retarded.
Identification of the mutations in the parents of a patient with a putative compound heterozygosity for acute intermittent porphyria
Authors: Picat C. , Delfau M. H. , de Rooij F. W. M. , Beukeveld G. J. J. , Wolthers B. G. , Wadman S. K. , Nordmann Y. , Grandchamp B. 
Published: June 2005

SummaryThe molecular abnormalities responsible for acute intermittent porphyria were investigated in both parents of a girl who was retrospectively diagnosed as having a homozygous form of the disease. The mutations in the parents are different from each other and both of them correspond to previously identified G to A changes in the coding part of the porphobilinogen deaminase mRNA. These point mutations lead to the presence of a catalytically‐defective but immunologically‐reactive enzyme. Our results support the conclusion that the propositus girl may represent the first case of compound heterozygosity for acute intermittent porphyria alleles.
Coexistent hereditary coproporphyria and congenital erythropoietic porphyria (Günther disease)
Authors: Nordmann Y. , Amram D. , Deybach J. C. , Phung L. N. , Lesbros D. 
Published: June 2005

SummaryWe present data on one patient with an inheritance pattern for two porphyrias. From her mother she inherited the trait of hereditary coproporphyria; from both parents she inherited the trait of congenital erythropoietic porphyria (Günther disease). Enzyme studies confirmed this new type of dual porphyria.
Identification of a single nucleotide substitution in the coding sequence ofin vitro amplified cDNA from a patient with partial HPRT deficiency (HPRTBrisbane)
Authors: Gordon R. B. , Sculley D. G. , Dawson P. A. , Beacham I. R. , Emmerson B. T. 
Published: June 2005

SummaryThe change in genomic DNA responsible for HPRT deficiency has been determined in a patient with urate overproduction and gout. In erythrocyte cell lysates, this patient had approximately 10% of normal HPRT enzyme activity and 26% of immunoidentical HPRT protein. Cultured lymphoblasts derived from this patient were used to extract mRNA. This was reverse transcribed to cDNA, which was then amplified using the polymerase chain reaction. The resulting DNA was cloned and the nucleotide sequence determined. In addition a portion of the sequence was derived from cloned double‐stranded cDNA prepared by conventional first and second strand synthesis. A single nucleotide base change (a C → T transition) was detected, which predicts an amino acid substitution of isoleucine for threonine at amino acid 168 of the HPRT protein. The nucleotide substitution creates aBamHI site, confirming a restriction fragment length polymorphism previously reported in this patient.
Pyrimidine 5′‐nucleotidase activity in normal and deficient human lymphoblastoid cells
Authors: Hopkinson D. A. , Swallow D. M. , Marinaki A. , Harley E. H. 
Published: June 2005

SummaryTwo distinct pyrimidine 5′‐nucleotidases (UMPH‐1 and UMPH‐2) have previously been detected in human erythrocytes; UMPH‐1 is deficient in a haemolytic anaemia, while UMPH‐2 is unaffected. Only the erythrocyte shows pathological effects in this disorder. Here we have studied lymphoblastoid cell lines from control and UMPH‐1 deficient patients to determine whether UMPH‐1 can be detected in lymphoblastoid cells and whether the deficiency of UMPH‐1 results in any measurable metabolic effects. Both UMPH‐1 and a UMPH‐2‐like activity were found to be present in control lymphoblastoid cells. UMPH‐1 was undetectable in the patients' cells; minor but significant changes were found in the pyrimidine nucleotide and nucleoside pools in the cells.
Heterogeneity of phenylketonuria at the clinical, protein and DNA levels
Authors: Cotton R. G. H. 
Published: June 2005

SummaryThe cloning of the phenylalanine hydroxylase gene and cDNA has potentially allowed the complete characterization of patients with phenylketonuria and already many mutations have been defined. Parents of patients now have the option of prenatal diagnosis. The 18 mutations defined so far indicate enormous heterogeneity not only within particular populations but also between populations. These mutations give little indication as to the locations of the amino acid residues important in enzyme function but one‐third of the mutations are in exon 7 which may be indicating the importance of the region coded by this exon in the protein.
Deletions of the mitochondrial genome
Authors: Harding A. E. , Hammans S. R. 
Published: June 2005

SummarySingle large deletions of mitochondrial DNA are found in the muscle of about 40% of patients with mitochondrial myopathies, and are detectable in both blood and muscle in Pearson syndrome. In mitochondrial myopathies, there is a close association between the presence of deletions and involvement of extra‐ocular muscles, together with other features of the Kearns‐Sayre syndrome. Deletions appear to arise as fresh mutations in the vast majority of patients and are often flanked by direct repeats up to 13 nucleotides in length. They should affect translation of all mitochondrially encoded components of the respiratory chain, but there is evidence to suggest that intramitochondrial complementation occurs in some cases.
Duplications of mitochondrial DNA: Implications for pathogenesis
Authors: Poulton J. 
Published: June 2005

SummaryThis paper describes the mapping data obtained on two patients in whom there was clear evidence for a rearrangement of mitochondrial DNA, using restriction enzyme analysis of DNA from whole blood and of polymerase chain reaction products. This suggested that a direct tandem duplication was present, and this was confirmed by sequence analysis of the junction fragment between duplicated segments. In each case the gene for cytochrome oxidase subunit I (MTCOX1) was interrupted, creating reading frames which, if transcribed and translated, would result in truncated versions of this peptide.Heteroplasmy and mosaicism for the abnormal mtDNA population were apparent. Preliminary data also suggest that high‐molecular‐weight rearrangements of the duplicated region are present in all tissues.The hypothesis that these duplicated genomes caused the phenotype was investigated by examining the distribution of duplicated genomes in various tissues using Southern hybridization and by RNA analysis. This included Northern blotting and cDNA sequencing.In order to investigate the origins of the duplicated mtDNAs, their distribution in different cells within a tissue was documented using the polymerase chain reaction.
The X chromosome in development in mouse and man
Authors: Monk M. 
Published: June 2005

SummaryIn mammals, dosage compensation for X‐linked genes between males and females is achieved by the inactivation of one of the X chromosomes in females. The inactivation event occurs early in development in all cells of the female mouse embryo and is stable and heritable in somatic cells. However, in the primordial germ cells, reactivation occurs around the time of meiosis. Owing to random inactivation in somatic cells, all female mice and humans are mosaic for X‐linked gene function. Variable mosaicism can result in expression of disease in human females heterozygous for an X‐linked gene defect.In the extra‐embryonic lineages of female mouse embryos, and in the somatic cells of female marsupials, the paternally inherited X chromosome is preferentially inactivated. The X chromosomes in the egg and sperm must be differentially marked or imprinted, so that they are distinguished by the inactivation mechanism in these tissues.Initiation of inactivation of an entire X chromosome appears to spread from a single X‐inactivation centre and may involve the recently discovered gene,XIST, which is expressed only from the inactive X chromosome. The maintenance of inactivation of certain household genes on the inactive X chromosome involves methylation of CpG islands in their 5' regions. Critical CpG sites are methylated at, or very close to, the time of inactivation in development.The mouse and the human X chromosomes carry the same genes but their arrangement is different and there are some genes in the pairing segment and elsewhere on the human X chromosome which can escape inactivation. Regions of homology between the mouse and human X chromosomes allow prediction of the map positions of homologous genes and provide mouse models of genetic disease in the human.
Duchenne muscular dystrophy: Gene and gene product; mechanism of mutation in the gene
Authors: Worton R. G. 
Published: June 2005

SummaryThe X‐linked gene responsible for Duchenne muscular dystrophy encodes dystrophin, a high‐molecular‐weight cytoskeletal protein. Studies in several laboratories have revealed deletion of one or more exons in 60% of affected boys; quantitative analysis in our laboratory has detected duplication of exons in another 6%. The severe Duchenne phenotype is associated with deletions or duplications that shift the reading frame of the message, whereas the milder Becker muscular dytrophy is associated with deletions or duplications that maintain the reading frame. Patients who have neither deletion nor duplication may have nonsense mutations, one of which has been detected by predicting the site of the mutation from the size of the truncated protein. Rare females with the disease have a translocation that disrupts the dystrophin gene on one X chromosome and causes non‐random inactivation of the normal X, resulting in the expression of the disease.The high frequency of new mutation provides an opportunity to study the mechanism of chromosomal rearrangement that is characteristic of the disease. Our laboratory has focused on the translocations in females and on duplications in affected males. The X‐autosome translocations of affected females are allde novo events that originated in the paternal set of chromosomes. Molecular characterization of the translocation junctions revealed reciprocal translocation with both deletion and addition of nucleotides at the junction, suggestive of a breakage and reunion mechanism. Duplications studied to date are all tandem in nature and sequence analysis of duplication junctions has revealed both homologous and non‐homologous recombination. Marker segregation analysis has revealed that five out of five duplications originated in a single X chromosome of one of the maternal grandparents, suggesting that the recombination event is unequal sister chromatid exchange.
Ornithine carbamoyl transferase deficiency: Findings, models and problems
Authors: Bachmann C. 
Published: June 2005

SummaryThe initial clinical symptoms of ornithine carbamoyl transferase deficiency depend on the age of onset. Respiratory distress on the first day of life does not allow exclusion of OCT deficiency in the individual patient. The acid‐base status is not useful as a discriminant between urea‐cycle disorders and organic acidurias. Beyond the neonatal age, a second period of increased risk for often lethal hyperammonaemic crises is found between 12 and 15 years of age. For definite diagnosis (pre‐ and postnatal) of heterozygotes the quantity of tissue obtained should be sufficient to obtain a representative sample for a mosaic structure. Experimental work gives some clues for the interpretation of reversible symptoms of hyperammonaemia. The increased transport of tryptophan at the blood‐brain barrier in presence of increased glutamine concentration in tissue appears to depend on intact gammaglutamyl transpeptidase in brain microvessels and involves at least in part the L‐carrier. Animal research on the mechanisms leading to irreversible damage in hyperammonaemia should be encouraged in order to define reliable predictive criteria for clinical decisions.
Pyruvate dehydrogenase E1α deficiency
Authors: Brown G. K. 
Published: June 2005

SummaryPyruvate dehydrogenase (PDH) deficiency has long been recognized as the most common defined cause of primary lactic acidosis in infancy and early childhood. More recently, it has also been described in patients with subacute/chronic neurodegenerative disease without significant metabolic acidosis. The great majority of cases of PDH deficiency result from a genetic defect in the E1α subunit of the complex. PDH E1α deficiency is an X‐linked inborn error of metabolism in which a high proportion of heterozygous females manifest the condition. In this review of 29 patients with PDH E1α deficiency, particular emphasis is given to those aspects of the disorder which are specifically related to the X chromosome location of the PDH E1α gene. These include the broad spectrum of clinical presentations and problems of diagnosis, especially antenatal diagnosis, in females.