bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case Report: Severe phenotype despite high residual glutaryl‐CoA dehydrogenase activity: A novel mutation in a Turkish patient with glutaric aciduria type I
Authors: Mühlhausen C. , Christensen E. , Schwartz M. , Muschol N. , Ullrich K. , Lukacs Z. 
Published: December 2003

AbstractWe report the first patient with the homozygous GCDH mutation M263V, displaying a high residual activity in fibroblasts of 30%, but presenting with a severe clinical phenotype.
Prerequisites and strategies for prenatal diagnosis of respiratory chain deficiency in chorionic villi
Authors: Niers L. , Heuvel L. van den , Trijbels F. , Sengers R. , Smeitink J. 
Published: December 2003

AbstractSummary: Prenatal diagnosis for respiratory chain deficiencies is a complex procedure that requires a thorough diagnostic work‐up of the index patient. This includes confirmation of the clinical and metabolic evaluations through histological and enzymatic examinations of tissue biopsies. Prenatal diagnosis currently relies on biochemical assays of respiratory chain complexes in chorionic villi or amniocytes and is possible by mutation analysis of nuclear genes in a limited but increasing proportion of cases. Based on a recent survey of prenatal diagnosis in families with complex I and complex IV deficiencies, performed at Nijmegen Centre for Mitochondrial Disorders (NCMD), prerequisites and strategies for performing prenatal diagnosis have been developed to increase reliability. Biochemical investigations in chorionic villi can be done reliably if the respiratory chain enzyme deficiency is expressed in both skeletal muscle and skin fibroblasts to rule out tissue specificity. No mitochondrial DNA defects must be suspected or established. The NCMD does not offer prenatal diagnosis until all the prerequisites have been confirmed. We expect prenatal diagnosis at the molecular level to become more feasible in time as the mutational spectrum broadens with advances in medical research.
Efficacy of multidisciplinary approach in the treatment of two cases of nonclassical infantile glycogenosis type II
Authors: Bembi B. , Ciana G. , Martini C. , Benettoni A. , Gombacci A. , Deganuto M. , Pittis M. G. 
Published: December 2003

AbstractSummary: Glycogenosis type II (GSD II) is a lysosomal storage disorder due to acid α‐glucosidase deficiency. We report the results of a clinical multidisciplinary approach in two cases of nonclassical infantile GSD II. The patients received a high‐protein diet by percutaneous enteral gastrostomy (PEG), mechanical ventilatory support by tracheostomy and a physiotherapy programme. After 12 months of treatment, the patients showed significant improvement in muscular strength, nutritional state and respiratory function. Electrocardiography (ECG) and echocardiography improved in both patients. They maintained good clinical conditions for a period of 18 and 20 months, respectively; thereafter they presented with an elevated and persistent fever that was not correlated to a septic status and was not responsive to any antipyretic treatment. They deteriorated progressively and died. This study shows how a multidisciplinary approach may be useful to improve, even if temporarily, the clinical course of nonclassical infantile GSD II.
A model of neuronopathic Gaucher disease
Authors: Campbell P. E. , Harris C. M. , Sirimanna T. , Vellodi A. 
Published: December 2003

AbstractSummary: Gaucher disease (GD) is a lysosomal disorder involving the accumulation of glucocerebroside in the liver, spleen, bones and brain. Some patients exhibit only systemic disease (type I), but others have additional neurological signs which may lead to rapid neurodegeneration in infancy (type II) or take a more intermediate course (type III). Types II and III are collectively known as neuronopathic Gaucher disease (NGD). Systemic disease can now be treated by enzyme replacement therapy (ERT), but its efficacy in NGD is limited. Two infants who presented with bulbar palsy and failure to thrive were enzymatically diagnosed at 8 months with NGD. They were started on high‐dose ERT (120 IU/kg every 2 weeks). Both underwent serial oculomotor assessment and an audiological battery, including visual reinforcement audiometry, otoacoustic emissions, and the auditory brain stem response (ABR). Biochemical markers showed an incomplete systemic response to ERT, but neurological deterioration was relentless, leading to death at 16 and 25 months. Oculomotor testing revealed a complete absence of saccadic eye movements and progressive bilateral sixth nerve palsy in one. Audiological assessment revealed progressive deterioration of ABRs, but with normal peripheral hearing and otoacoustic emissions. Both infants showed neurological deterioration in spite of high‐dose ERT. The audiological findings suggested a loss of inner hair cell pathway function with preserved outer hair function, similar to what is seen in auditory neuropathy. The unusual pattern of audiological and oculomotor abnormalities is consistent with an excitotoxic mechanism predisposing nerve cells to glucocerebroside toxicity. Such excitotoxic damage may be amenable to direct therapeutic intervention.
Neonatal screening for biotinidase deficiency in Hungary: Clinical, biochemical and molecular studies
Authors: László Á. , Schuler É. Á. , Sallay É. , Endreffy E. , Somogyi Cs. , Várkonyi Á. , Havass Z. , Jansen K. P. , Wolf B. 
Published: December 2003

AbstractSummary: From 1989 to 2001, 1 336 145 newborns were screened for biotinidase deficiency in Hungary. Fifty‐eight children with the disorder were identified as enzyme‐deficient. We have characterized the clinical and biochemical features and mutations of 20 of these children. Eleven children had profound biotinidase deficiency, 7 had partial biotinidase deficiency, and 2 were found to be heterozygous for profound deficiency by mutation analysis. Seventeen different mutations were identified in this population including seven novel mutations. Six of these new mutations are missense, 245C>A, 334G>A, 652G>C, 832C>G, 1253G>C, 1511T>A, and one is a unique allelic double mutation [212T>C;236G>A]. Of five Romanian Gypsies, four were homozygous for the 1595C>T mutation and one was heterozygous for this mutation. Most of the children with profound deficiency have been asymptomatic on therapy; however, four exhibited minimal brain abnormalities, motor delay and abnormal blood chemistries. Compliance with therapy must be questioned in these cases. Of clinical importance, all of the children with partial deficiency exhibited mild symptoms at the time of diagnosis, at several weeks to months of age. These symptoms resolved following biotin therapy. This is in contrast to the experience in the United States, where the children with partial deficiency have been asymptomatic at the time of diagnosis. This finding further indicates that children with partial deficiency should be treated. The incidence of biotinidase deficiency in Hungary is more than twice that observed in a worldwide survey. These results indicate that newborn screening in Hungary is effective and warranted.
A neurological symptom survey of patients with type I Gaucher disease
Authors: Pastores G. M. , Barnett N. L. , Bathan P. , Kolodny E. H. 
Published: December 2003

AbstractSummary: Gaucher disease is an inborn error of glycosphingolipid metabolism resulting from deficiency of the lysosomal enzyme glucocerebrosidase. The majority of the patients (with type I disease) do not have primary central nervous system involvement. However, several studies have noted that secondary neurological complications may develop as a consequence of nerve root or spinal cord compression following vertebral body collapse or, for those with coagulation disorders, bleeding within confined compartments. An epidemiological survey was conducted to ascertain the incidence of neurological symptoms in patients with Gaucher disease type I (GD I). The survey included a review of the patients' medical history, an estimate of Gaucher disease severity according to a modified Symptom Severity Index (SSI), and completion of a questionnaire regarding their neurological status and Quality of Life (QoL) according to the SF‐36 Health Survey. Seventy‐three per cent of respondents were found to have experienced at least one neurological complaint in the preceding 3 months. Adult patients with Gaucher disease often have other medical problems unrelated to their primary diagnosis. Thus, the high incidence of neurological complaints in these patients may be attributable to concurrent medical problems and/or side‐effects from concomitant medications. These issues may influence patients' assessment of their disease severity and/or response to treatment.
Biochemical characterization of two mutants of human pyruvate dehydrogenase, F205L and T231A of the E1α subunit
Authors: Wu Yong‐Ge , Chen Wen‐Yang , Zhang Zi‐Wei , Yang Gui‐Zheng , Li Wei , Duggleby Ronald G. 
Published: December 2003

AbstractSummary: Mutations in the E1α subunit of the pyruvate dehydrogenase multienzyme complex may result in congenital lactic acidosis, but little is known about the consequences of these mutations at the enzymatic level. Here we characterize two mutants (F205L and T231A) of human pyruvate dehydrogenase in vitro, using the enzyme expressed in Escherichia coli. Wild‐type and mutant proteins were purified successfully and their kinetic parameters were measured. F205L shows impaired binding of the thiamin diphosphate cofactor, which may explain why patients carrying this mutation respond to high‐dose vitamin B1 therapy. T231A has very low activity and a greatly elevated Km for pyruvate, and this combination of effects would be expected to result in severe lactic acidosis. The results lead to a better understanding of the consequences of these mutations on the functional and structural properties of the enzyme, which may lead to improved therapies for patients carrying these mutations.
Case Report: Rhabdomyolysis in Glutaric Aciduria Type I
Authors: Chow S. L. , Rohan C. , Morris A. A. M. 
Published: December 2003

AbstractRecurrent rhabdomyolysis has previously been reported in one patient with glutaric aciduria type I. We report rhabdomyolysis in a second, unrelated patient, suggesting that there may be a specific association with this metabolic disorder.
Short Report: Tall stature and progressive overweight in mitochondrial encephalopathy
Authors: Morava E. , Hol F. A. , Janssen A. , Smeitink J. 
Published: December 2003

AbstractWe describe two children carrying an inherited T899C mutation in the mitochondrial ATPase 6 gene with mild encephalopathy and normal postnatal growth followed by tall stature and obesity. No familial tall stature, endocrine anomaly or advanced skeletal age were present. Failure to thrive is a characteristic finding in most patients with a mitochondrial disease. Our observations suggest that children with encephalomyopathy, even in the presence of a significant clinical overgrowth, should be screened for a possible defect in oxidative phosphorylation.
Phenylalanine can be detected in brain tissue of healthy subjects by 1H magnetic resonance spectroscopy
Authors: Pietz J. , Lutz T. , Zwygart K. , Hoffmann G. F. , Ebinger F. , Boesch C. , Kreis R. 
Published: December 2003

AbstractSummary: Transport of phenylalanine (Phe) and the other large neutral amino acids across the blood–brain barrier plays a crucial role in the pathogenesis of phenylketonuria (PKU). Thus, investigation of Phe transport kinetics by means of proton magnetic resonance spectroscopy (1H MRS) became an important research area in the mid 1990s. As 1H MRS measurements of brain phenylalanine are restricted to tissue concentrations above 100–150 µmol/kg wet weight, this approach was possible only in PKU patients, and comparison with healthy controls was not achieved. Using standardized single‐dose oral Phe loading in three healthy subjects, it was shown that Phe values increase steeply, peak at about 1 h post load, and decrease thereafter. In a single case study, repetitive Phe loading was then performed to achieve a plateau of high blood Phe concentrations for several hours. It was demonstrated that detection and monitoring of brain Phe concentrations is feasible by means of 1H MRS. This approach constitutes a prerequisite for describing carrier kinetics in health.
Enzyme replacement therapy in heterozygous females with Fabry disease: Results of a phase IIIB study
Authors: Baehner F. , Kampmann C. , Whybra C. , Miebach E. , Wiethoff C. M. , Beck M. 
Published: December 2003

AbstractSummary:Fabry disease is an X‐linked glycosphingolipid storage disorder caused by a deficiency of α‐galactosidase A. Affected patients experience debilitating neuropathic pain and have premature mortality due to renal failure, cardiovascular disease or cerebrovascular complications. The disease may be X‐linked dominant, since most females heterozygous for Fabry disease are affected clinically. We evaluated the safety, efficacy and pharmacokinetics of agalsidase alfa (Replagal) administered intravenously to female patients with Fabry disease in an open‐label, single‐centre study. Fifteen severely affected patients received agalsidase alfa at 0.2 mg/kg every other week for up to 55 weeks. Agalsidase alfa was safe and well‐tolerated in female patients. None of the patients developed antibodies or experienced an infusion reaction to agalsidase alfa. The pharmacokinetic profile of agalsidase alfa in female patients is comparable to the pharmacokinetics of agalsidase alfa in male patients. Mean urine sediment and plasma Gb3 levels decreased from baseline at 13, 27 and 41 weeks. A significant decrease in left ventricular mass from baseline was seen at weeks 27 (p= 0.003) and 41 (p= 0.039), and a significant reduction in QRS durations was seen at week 27 (p= 0.007). Furthermore, there was a significant improvement in quality of life. Renal function did not deteriorate in these 15 female patients over the 13‐ to 41‐week period of observation. We conclude that enzyme replacement therapy with agalsidase alfa was safe and effective in female patients heterozygous for Fabry disease.
Respiratory complex II defect in siblings associated with a symptomatic secondary block in fatty acid oxidation
Authors: Gargus J. J. , Boyle K. , Bocian M. , Roe D. S. , Vianey‐Saban C. , Roe C. R. 
Published: December 2003

AbstractSummary: The mitochondrial oxidative phosphorylation and fatty acid oxidation pathways have traditionally been considered independent major sources of cellular energy production; however, case reports of patients with specific enzymatic defects in either pathway have suggested the potential for a complex interference between the two. This study documents a new site of interference between the two pathways, a site in respiratory complex II capable of producing clinical signs of a block in fatty acid oxidation and reduced in vitro activity of acyl‐CoA dehydrogenases. The initial patient, and later her newborn sibling, had mildly dysmorphic features, lactic acidosis and a defect in mitochondrial respiratory complex II associated with many biochemical features of a block in fatty acid oxidation. Results of in vitro probing of intact fibroblasts from both patients with methyl[2H3]palmitate and L‐carnitine revealed greatly increased [2H3]butyrylcarnitine; however, the ratio of dehydrogenase activity with butyryl‐CoA with anti‐MCAD inactivating antibody (used to reveal SCAD‐specific activity) to that with octanoyl‐CoA was normal, excluding a selective SCAD or MCAD deficiency. Respiratory complex II was defective in both patients, with an absent thenoyltrifluoroacetone‐sensitive succinate Q reductase activity that was partially restored by supplementation with duroquinone. Although secondary, the block in fatty acid oxidation was a major management problem since attempts to provide essential fatty acids precipitated acidotic decompensations. This study reinforces the need to pursue broadly the primary genetic defect within these two pathways, making full use of increasingly available functional and molecular diagnostic tools.
Mutations in galactose‐1‐phosphate uridyltransferase gene in patients with idiopathic presenile cataract
Authors: Karas N. , Gobec L. , Pfeifer V. , Mlinar B. , Battelino T. , Lukac‐Bajalo J. 
Published: December 2003

AbstractSummary: Impaired activity of the enzyme galactose‐1‐phosphate uridyltransferase (GALT) has been proposed as a risk factor for idiopathic presenile cataract. A study was undertaken to determine the prevalence of the three most common mutations in the GALT gene (Q188R, K285N and N314D, including its variant Duarte‐2) in a group of Slovenian patients with idiopathic presenile cataract. GALT activity was determined in the erythrocytes of 30 cataract patients. DNA was isolated from their blood and analysed for Q188R, K285N and N314D mutations and IVS5−24G>A intronic variation by means of polymerase chain reaction and digestion with restriction enzymes. The average GALT activity of the cataract group was 19.5±4.9 U/g Hb, which is lower than the normal range (p = 0.034). Frequencies of Q188R, K285N, N314D and Duarte‐2 alleles in the cataract group were 0.00%, 5.0%, 11.7% and 3.3%, respectively. Only the frequency of the K285N mutation was significantly higher in the patient group than in the control group (p = 0.0244). Our results support the reported association of decreased GALT activity with idiopathic presenile cataract. Molecular analysis indicates that, in the Slovenian population, this association is linked to the K285N mutation, which is neonatally benign in heterozygotes.
Short Report: Normalization of low biotinidase activity in a child with biotin deficiency after biotin supplementation
Authors: Kimura M. , Fukui T. , Tagami Y. , Fujiwaki T. , Yokoyama M. , Ishioka C. , Kumasaka K. , Terada N. , Yamaguchi S. 
Published: December 2003

AbstractWe report findings in a Japanese boy with severe skin rash attributable to biotin deficiency. The patient had an intracranial malformation and developed biotin deficiency due to tube feeding with a single formula for over one year. Results of urinary organic acid analysis were consistent with multiple carboxylase deficiency, and low biotinidase activity was also observed. After biotin supplementation, the skin rash improved and biotinidase activity normalized. We speculate that biotin is one regulating factor in the biosynthesis of biotinidase.
Environmental Unpredictability and the Value of Social Information for Foraging Starlings
Authors: Rafacz Michelle , Templeton Jennifer J. 
Published: December 2003

AbstractEnvironmental and behavioral cues are useful sources of information that allow group foraging individuals to improve their foraging success. Few studies to date, however, have examined how varying degrees of environmental unpredictability may affect when and how individuals use the social information they obtain in foraging groups. In this experiment, European starlings (Sturnus vulgaris) were tested to determine in which type of environment, predictable or unpredictable, social information would be the most valuable. Subjects were placed under one of four conditions: an unpredictable environment with either (1) an informing demonstrator bird or (2) an uninforming demonstrator; or a predictable environment with either (3) an informing demonstrator or (4) an uninforming demonstrator. Environmental predictability was manipulated by altering the meaning of available color cues. Subjects in the unpredictable environment that had an informing demonstrator performed significantly better than subjects in an unpredictable environment with an uninforming demonstrator, although only on the second day of testing. Subjects in both the predictable conditions performed similarly to each other. The results suggest that social information is more valuable to individuals in an unpredictable environment than it is in a predictable environment; however, there appears to be a time lag in the ability of the birds to recognize the value of this information.
The Role of Ultraviolet‐A Reflectance and Ultraviolet‐A‐Induced Fluorescence in Budgerigar Mate Choice
Authors: Pearn Sophie M. , Bennett Andrew T. D. , Cuthill Innes C. 
Published: December 2003

AbstractMany parrots have plumage that either reflects strongly in the ultraviolet‐A (UVA) waveband, between 315–400 nm, or exhibits UVA‐induced fluorescence. Previous experimental work on budgerigars (Melopsittacus undulatus) suggests that UVA reflectance plays a role in mate choice, as in other diurnal birds, but evidence for fluorescent cues playing a role is unconvincing. Here we report two experiments on budgerigars, designed to determine whether fluorescent cues play a role in signalling when UVA reflectances are absent, an approach which separates removal of UVA reflectance from removal of fluorescence. First, we determined whether the choices of different females are correlated under these treatment conditions. Secondly, we investigated female preferences for fluorescing and non‐fluorescing males when UVA reflections are absent, to determine whether the yellow emissions of fluorescence are playing a role in mate choice. Results from experiment 1 do not suggest that females agree on which males are attractive when UVA reflectances are absent, with only half of the subjects choosing the same male. Neither did different females make the same choices in experiment 2. This lack of agreement provides further evidence that UVA reflectances from males play an important role in female choice in this species. Experiment 2 provides no evidence to suggest that UVA‐induced fluorescence plays a role in mate choice. Overall, our study supports previous findings showing that UVA reflectance plays a role in sexual signalling in this species, but provides no evidence to suggest the same for fluorescence when UVA reflectances are absent.
In vitro cariogenic potential of Candida albicans
Authors: Nikawa H. , Yamashiro H. , Makihira S. , Nishimura M. , Egusa H. , Furukawa M. , Setijanto D. , Hamada T. 
Published: November 2003

SummaryThe adherence and dissociation of Candida albicans, C. tropicalis, Streptococcus mutans and S. sanguis to six substrates including hydroxylapatite (HAP) which exhibit various hydrophobicity, was examined by the use of a bioluminescent adenosine triphosphate (ATP) assay. Dissolution of HAP by C. albicans or S. mutans was determined spectrophotometrically by the use of o‐cresolphthalein complexone. In the adherence of C. tropicalis, S. mutans and S. sanguis, the amount of adherent cells correlated with the hydrophobicity of the substrates. In contrast, the adherence of C. albicans to HAP was extraordinary high, although the adherence of the fungi also correlated with the hydrophobicity of the substrates, except for HAP. The yeasts attached to HAP was effectively removed by high concentration of either phosphate or calcium ions. The amount of calcium‐release from HAP caused by C. albicans and S. mutans was 113 μg ml−1 (final pH = 3.45), and 5.4 μg ml−1 (final pH 4.81), respectively and the maximum growth of C. albicans and S. mutans was 107 cfu ml−1 and 7.4 × 1012 cfu ml−1, respectively. The results, taken together, suggest that C. albicans adhere to HAP specifically through electrostatic interaction, and that, in a much smaller number (1.0/7.4 × 105), C. albicans possesses the ability to dissolve HAP to a greater extent (approximately 20‐fold) when compared with S. mutans.