bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biochemical and molecular basis for mitochondrial cardiomyopathy in neonates and children
Authors: Marin‐Garcia J. , Ananthakrishnan R. , Goldenthal M. J. , Pierpont M. E. 
Published: December 2002

AbstractDefects in myocardial bioenergetics have been reported in patients with cardiomyopathy but their molecular basis and role in pathophysiology remain unclear. We sought to establish a molecular basis for cardiac mitochondrial respiratory enzyme abnormalities frequently present (75%) in a group of 16 children (including 2 neonates) with end‐stage cardiomyopathy. Decreased specific activity levels were found in complexes I, III, IV and V but not in II, the only complex that is entirely nuclear encoded. Sequence analysis of cardiac mtDNA revealed 4 patients harbouring heteroplasmic mtDNA mutations in cytb, tRNAArg, and ND5 at highly conserved positions. These mutations were present neither in controls nor in patients without enzymatic defect. In addition, 4 patients exhibited marked reduction in cardiac mtDNA levels. The basis for respiratory enzyme abnormalities can be explained in a subset of our patients as a result of either pathogenic mtDNA mutation or depletion. Patients harbouring both DNA and enzymatic defects fulfil rigorous criteria defining mitochondrial cardiomyopathy.
Brain phenylalanine concentration in the management of adults with phenylketonuria
Authors: Moats R. A. , Koch R. , Moseley K. , Guldberg P. , Guttler F. , Boles R. G. , Nelson M. D. 
Published: December 2002

AbstractDiagnosis by newborn screening and the implementation of a phenylalanine‐restricted diet have resulted in normal neurological development in approximately 10 000 persons with phenylketonuria (PKU) in the United States. While it is accepted that a phenylalanine‐restricted diet is necessary in childhood, the recommended concentration of phenylalanine in the blood varies. Clinicians now must make recommendations for adults with PKU who probably tolerate higher levels of phenylalanine than children. This factor, quality of life issues, the expense of the diet, and varying genetic and socio‐economic backgrounds, make the choice of dietary recommendations difficult.Molecular analysis of the mutations in PKU has provided insight but has not resulted in clear recommendations for phenylalanine concentration in the blood. Magnetic resonance imaging has provided the recognition that white‐matter changes are present in PKU. However, owing to poor correlation of white‐matter changes with clinical factors, analysis of white‐matter changes has not proved useful. We hypothesize that measurement of brain phenylalanine directly will aid in clinical decision making.Twenty‐one subjects with PKU had blood and brain phenylalanine measured simultaneously. Fifteen were randomly selected, 2 were examined for clinical reasons and 4 exceptional patients were chosen because they had maintained high IQs, despite having high historic blood concentrations and having been off the diet for at least 10 years. The correlation of blood and brain phenylalanine is in general poor. However, the four exceptional patients all had relatively low concentrations of phenylalanine in their brains compared to their blood. We suggest that their good clinical status, despite high historic blood levels, is due to their comparatively low brain levels of phenylalanine. We further suggest that measurement of brain phenylalanine concentration is useful in the management of PKU patients.
Mitochondrial DNA mutations at nucleotide 8993 show a lack of tissue‐ or age‐related variation
Authors: White S. L. , Shanske S. , McGill J. J. , Mountain H. , Geraghty M. T. , DiMauro S. , Dahl H.‐H. M. , Thorburn D. R. 
Published: December 2002

AbstractTwo pathogenic mitochondrial DNA mutations, a T‐to‐G substitution (8993T>G) and a T‐to‐C substitution (8993T>C), at nucleotide 8993 have been reported. We describe 13 pedigrees with mitochondrial DNA mutations at nucleotide 8993; 10 pedigrees with the 8993T>G mutation and three with the 8993T>C mutation. Prenatal diagnosis of the nucleotide 8993 mutations is technically possible. However, there are three major concerns: (i) that there is variation in mutant loads among tissues; (ii) that the mutant load in a tissue may change over time; and (iii) that the genotype–phenotype correlation is not clearly understood. We have used the 13 pedigrees to determine specifically the extent of tissue‐ and age‐related variation of the two mutations at nucleotide 8993 in the mitochondrial DNA. The tissue variation was investigated by analysing two or more different tissues from a total of 18 individuals. The age‐related variation of the mutation was investigated by comparing the amount of both mutations in blood taken at birth and at a later age. No substantial tissue variation was found, nor was there any substantial change in the proportion of either mutation over periods of 8–23 years in the four individuals studied. In addition, we noted that two features were remarkably common in families with nucleotide 8993 mutations, namely (i) unexplained infant death (8 cases in 13 pedigrees), and (ii) de novo mutations (5 of the 10 8993T>G pedigrees).
Lysosomal transport disorders
Authors: Mancini G. M. S. , Havelaar A. C. , Verheijen F. W. 
Published: December 2002

AbstractIn the group of lysosomal storage diseases, transport disorders occupy a special place because they represent rare examples of inborn errors of metabolism caused by a defect of an intracellular membrane transporter. In particular, two disorders are caused by a proven defect in carrier‐mediated transport of metabolites: cystinosis and the group of sialic acid storage disorders (SASD). The recent identification of the gene mutations for both disorders will improve patient diagnosis and shed light on new physiological mechanisms of intracellular trafficking.
Dramatic improvement in mitochondrial cardiomyopathy following treatment with idebenone
Authors: Lerman‐Sagie T. , Rustin P. , Lev D. , Yanoov M. , Leshinsky‐Silver E. , Sagie A. , Ben‐Gal T. , Munnich A. 
Published: December 2002

AbstractIdebenone, a synthetic analogue of coenzyme Q10, has been shown to improve cardiac function in patients with Friedreich ataxia and a deficiency of respiratory chain complexes I–III. We describe a woman with severe combined right and left heart failure due to a mitochondrial cardiomyopathy. The patient underwent an endomyocardial biopsy as part of an evaluation for cardiac transplantation. It showed severely decreased respiratory complex activities dependent on CoQ, pointing to CoQ depletion. Following idebenone treatment there was a dramatic improvement in her clinical status with resolution of the heart failure.
Behavioural and emotional problems in early‐treated adolescents with phenylketonuria in comparison with diabetic patients and healthy controls
Authors: Weglage J. , Grenzebach M. , Pietsch M. , Feldmann R. , Linnenbank R. , Denecke J. , Koch H. G. 
Published: December 2002

AbstractEven early‐treated patients with phenylketonuria (PKU) have a higher risk of psychosocial maladjustment. This study was performed to determine whether emotional and behavioural problems are specific in phenylketonurics and whether they depend on the quality of biochemical control. This comparative study covered 42 PKU patients aged 10–18 years (mean 14.7 years) and 42 diabetic patients matched for sex, age and socioeconomic status. Patients' groups were compared with a control sample of healthy controls (n=2900) from an epidemiological study. We used the Child Behavior Check List (CBCL) according to Achenbach, intelligence quotient (IQ) test according to Weiss, and monitoring of blood phenylalanine concentrations and HBA1 concentrations. Internalizing problems such as depressive mood, anxiety, physical complaints or social isolation were significantly elevated in both phenylketonuric and diabetic patients, whereas externalizing problems were not. The two patient groups did not differ significantly either in the degree or in the pattern of their psychological profile. In both groups no significant correlations could be computed between the psychological characteristics and the biochemical control, the IQ, and the socioeconomic status. No patient was undergoing psychiatric treatment or psychotherapy. Our results strongly support a psychological perspective for the development of behavioural and emotional problems in both phenylketonuric and diabetic patients. Thus, medical treatment should be accompanied by psychological support for the families.
Behaviour and school achievement in patients with early and continuously treated phenylketonuria
Authors: Stemerdink B. A. , Kalverboer A. F. , van der Meere J. J. , van der Molen M. W. , Huisman J. , de Jong L. W. A. , Slijper F. M. E. , Verkerk P. H. , van Spronsen F. J. 
Published: December 2002

AbstractThirty patients with early and continuously treated phenylketonuria (PKU) between 8 and 20 years of age were compared with 30 controls, matched individually for age, sex, and educational level of both parents, on behaviour rating scales for parents and teachers as well as a school achievement scale. PKU patients, as a group, demonstrated more problems in task‐oriented behaviour and average academic performance than did matched controls. Interestingly, whereas male PKU patients were rated significantly lower on introversion by their teachers, female patients were rated significantly higher on introversion and lower on extraversion than matched controls. This sex difference was also reflected in the relationship between measures of dietary control and the behaviour clusters, suggesting that male and female patients respond differently to elevated Phe levels or the stress associated with PKU. The teacher rating on average academic performance of the PKU patients was associated with recent level of dietary control, which suggests that it might be improved by more strict adherence to the diet. In addition, academic performance correlated negatively with the behaviour cluster negative task orientation. Further studies are recommended to obtain a more complete evaluation of this relationship and to replicate the current findings on larger samples.
Genotypes and phenotypes of patients in the UK with carbohydrate‐deficient glycoprotein syndrome type 1
Authors: Imtiaz F. , Worthington V. , Champion M. , Beesley C. , Charlwood J. , Clayton P. , Keir G. , Mian N. , Winchester B. 
Published: December 2002

Abstract18 UK patients (14 families) have been diagnosed with the carbohydrate‐deficient glycoprotein syndrome (CDGS), type 1, on the basis of their clinical symptoms and/or abnormal electrophoretic patterns of serum transferrin. Eleven out of the 16 infants died before the age of 2 years. Patients from 12 families had a typical type 1 transferrin profile but one had a variant profile and another, who had many of the clinical features of CDGS type 1, had a normal profile. Eleven of the patients (10 families) with the typical type 1 profile had a deficiency of phosphomannomutase (PMM), (CDGS type 1a) but there was no correlation between residual enzyme activity and severity of disease. All these patients were compound heterozygotes for mutations in the phosphomannomutase (PMM2) gene, with 7 out of the 10 families having the common R141H mutation. Eight different mutations were found, including three novel ones. There was no correlation between genotype and phenotype, although siblings had similar phenotypes. Three patients, including the one with the normal transferrin profile, did not have a deficiency of phosphomannomutase or phosphomannose isomerase (CDGS 1b).
Acylcarnitines in plasma and blood spots of patients with long‐chain 3‐hydroxyacyl‐coenzyme A dehydrogenase defiency
Authors: Van Hove J. L. K. , Kahler S. G. , Feezor M. D. , Ramakrishna J. P. , Hart P. , Treem W. R. , Shen J.‐J. , Matern D. , Millington D. S. 
Published: December 2002

AbstractThe acylcarnitines in plasma and blood spots of 23 patients with proven deficiency of long‐chain 3‐hydroxyacylcoenzyme A dehydrogenase were reviewed. Long‐chain 3‐hydroxyacylcarnitines of C14:1, C14, C16 and C18:1 chain length, and long‐chain acylcarnitines of C12, C14:1, C14, C16, C18:2 and C18:1 chain length were elevated. Acetylcarnitine was decreased. In plasma, elevation of hydroxy‐C18:1 acylcarnitine over the 95th centile of controls, in combination with an elevation of two of the three acylcarnitines C14, C14:1 and hydroxy‐C16, identified over 85% of patients with high specificity (less than 0.1% false positive rate). High endogenous levels of long‐chain acylcarnitines in normal erythrocytes reduced the diagnostic specificity in blood spots compared with plasma samples. The results were also diagnostic in asymptomatic patients, and were not influenced by genotype. Treatment with diet low in fat and high in medium‐chain triglyceride decreased all disease‐specific acylcarnitines, often to normal, suggesting that this assay is useful in treatment monitoring.
Psychiatric symptoms of inherited metabolic disease
Authors: Estrov Y. , Scaglia F. , Bodamer O. A. F. 
Published: December 2002

AbstractInborn errors of metabolism often present with a variety of psychiatric symptoms. With improved diagnosis and treatment options, many patients have increased lifespans; consequently, issues of long‐term quality of life are coming to the forefront. Mental health concerns are among these issues. To demonstrate the connection between the course of metabolic disease and its psychiatric manifestations, four different inborn errors of metabolism are reviewed: phenylketonuria, Wilson disease, acute intermittent porphyria, and metachromatic leukodystrophy.
Rolipram does not normalize very long‐chain fatty acid levels in adrenoleukodystrophy protein‐deficient fibroblasts and mice
Authors: Netik A. , Hobel A. , Rauschka H. , Molzer B. , Forss‐Petter S. , Berger J. 
Published: December 2002

AbstractIn its severe form, X‐linked adrenoleukodystrophy (X‐ALD) is a lethal neurodegenerative disorder with inflammatory demyelination, in which defective peroxisomal β‐oxidation causes accumulation of very long‐chain fatty acids (VLCFA) in tissues and plasma, in particular in the nervous system and adrenal glands. Recently, several drugs have been reported to reduce VLCFA in cultured human fibroblasts of X‐ALD patients, and therefore to be potential candidates for novel therapeutic treatments in X‐ALD. Among the most promising of these substances is the antidepressant rolipram, because of favourable adverse event profile in clinical studies and its additionally reported anti‐inflammatory action. To further elucidate the effects of rolipram on peroxisomal β‐oxidation and VLCFA accumulation, we administered rolipram orally in the diet to ALD protein‐deficient mice and ALD protein‐deficient cultured human and mouse fibroblasts and assayed the accumulation of VLCFA. In contrast to the previously reported reduction of VLCFA, our data did not demonstrate a decrease in VLCFA content either in vivo or in vitro. NMR spectroscopic analysis verified the structural integrity and purity of the rolipram used here, thus excluding inauthenticity as a reason for the discrepancy. We therefore suggest that rolipram should be excluded from the current list of potential therapeutic agents for X‐ALD.
Blood lipids and endothelial function in glycogen storage disease type III
Authors: Hershkovitz E. , Donald A. , Mullen M. , Lee P. J. , Leonard J. V. 
Published: December 2002

AbstractWe have assessed early indicators of arterial disease in patients with glycogen storage disease type III (GSD III; McKusick 232400), investigating the plasma lipid and lipoprotein profile and endothelial function. Eleven patients, aged 10–39 years, were recruited together with age‐, sex‐ and smoking status‐matched controls. Brachial artery responses were assessed by high‐resolution ultrasonographic measurement of the diameter of the brachial artery at baseline, after reactive hyperaemia and in response to sublingual glyceryl trinitrate (GTN).The means of plasma cholesterol (total and HDL and LDL subfractions), triglycerides, apo‐A1, apo‐B, Lp(a) and the atherogenic index were similar in both groups. Cardiac troponin I was below the lower limits of detection (<0.03g/L) in all subjects. The GSD III patients had similar body mass index (BMI) and brachial artery diameter to the control group (BMI 22.6±5.6 vs 22.3±5kg/m2; brachial artery diameter 3.4±0.5 vs 3±0.7mm). When compared to the baseline diameter, the maximal flow‐mediated dilatation of the brachial artery after reactive hyperaemia was 9.3±2.1% (mean±SD) in the GSD III patients and 6.5±3.5% in the control group, a difference of 1.8% (95% CI 0.07% to 5.5%). The maximal dilatation of the brachial artery after GTN administration was 18.3±6.4% in the GSD III patients and 17.9±6.5% in the control group, a difference of 0.4% (95% CI –6.9% to 7.7%.In conclusion, we found no evidence of abnormal plasma lipid and lipoprotein profile or endothelial dysfunction in patients with GSD III. They are unlikely to be at increased risk of premature atherosclerosis.
Features of carnitine palmitoyltransferase type I deficiency
Authors: Olpin S. E. , Allen J. , Bonham J. R. , Clark S. , Clayton P. T. , Calvin J. , Downing M. , Ives K. , Jones S. , Manning N. J. , Pollitt R. J. , Standing S. J. , Tanner M. S. 
Published: December 2002

AbstractCarnitine palmitoyltransferase type I (CPT I) is unique among long‐chain fatty acid oxidation enzymes in that there are two tissue‐specific isoforms, ‘hepatic’ and ‘muscle’, which are encoded by two separate genes. The ‘hepatic’ isoform is expressed in liver, kidney and fibroblasts and at low levels in the heart, while the other isoform occurs in skeletal muscle and is the predominant form in heart. Reported patients with CPT I deficiency lack activity of the hepatic isoform and present before 30 months of age with hypoketotic hypoglycaemia, hepatomegaly with raised transaminases, seizures and coma. We discuss four new cases in three families showing, variously, renal tubular acidosis, transient hyperlipidaemia and, paradoxically, myopathy with elevated creatinine kinase or cardiac involvement in the neonatal period as additional features that deserve wider recognition.
Acylcarnitines in fibroblasts of patients with long‐chain 3‐hydroxyacyl‐CoA dehydrogenase deficiency and other fatty acid oxidation disorders
Authors: Shen J. J. , Matern D. , Millington D. S. , Hillman S. , Feezor M. D. , Bennett M. J. , Qumsiyeh M. , Kahler S. G. , Chen Y.‐T. , Van Hove J. L. K. 
Published: December 2002

AbstractMitochondrial fatty acid oxidation disorders cause hypoglycaemia, hepatic dysfunction, myopathy, cardiomyopathy and encephalopathy. Despite their recognition for more than 15 years, diagnosis and treatment remain difficult. To help design rational diagnostic and therapeutic strategies, we studied the pathophysiology of accumulating metabolites in a whole‐cell system. Acylcarnitines were quantified in cells and media of cultured fibroblasts after incubation with L‐carnitine and fatty acids. Following incubation with palmitate, long‐chain 3‐hydroxyacyl‐CoA dehydrogenase (LCHAD)‐deficient fibroblasts compared with controls showed elevation of hydroxypalmitoyl‐ and palmitoylcarnitine and reduction of C10‐ and shorter acylcarnitines, and following incubation with linoleate an increase in C14:2‐, C18:2‐ and hydroxy‐C18:2‐acylcarnitines and reduction in C10:1‐acylcarnitines. Hydroxyacylcarnitines remained more intracellular compared to corresponding saturated acylcarnitines. Incubation with decanoate and octanoate showed absence of hydroxylated acylcarnitines and correction of secondary metabolic disturbances, suggesting that optimal treatment should include medium‐chain triglycerides of these chain lengths. Fibroblasts of patients with other fatty acid oxidation disorders showed distinct elevations of disease‐specific acylcarnitines. This acylcarnitine analysis allows the diagnosis of LCHAD deficiency and its differentiation from other fatty acid oxidation disorders, which can pose difficulties in vivo. The strategy has allowed in‐depth analysis with different substrates, providing suggestions for the rational design of treatment trials.
Do Coping Styles Differ Across Sociocultural Groups? The Role of Measurement Equivalence in Making This Judgment
Authors: Prelow Hazel M. , Tein Jenn-Yun , Roosa Mark W. , Wood Jennifer 
Published: December 2002

AbstractCross‐sociocultural group measurement equivalency is an important issue that generally has not been studied in the coping literature. Measurement equivalency of the COPE (Carver, Scheier, & Weintraub, 1989) was assessed across two sociocultural groups, a sample of 100 Anglo middle‐class divorced mothers and a sample of 122 low‐income Mexican American/Mexican immigrant mothers. A series of restrictive confirmatory factor analyses revealed that seven of the COPE's subscales may be measuring the same underlying construct across populations. However, scores derived from the subscales may not represent the same magnitude of the construct in these two groups. This study makes an important first step in furthering the understanding of coping strategies in low‐income Mexican American/Mexican immigrant mothers. This study also illustrates the importance of testing for measurement equivalency before conducting comparative research in disparate populations.
The Roles of Ethnicity and School Context in Predicting Children's Victimization by Peers
Authors: Hanish Laura D. , Guerra Nancy G. 
Published: December 2002

AbstractThis study examines the prevalence, stability, and contextual correlates of peer victimization in a sample of African‐American, Hispanic, and non‐Hispanic White urban elementary school‐age children. A total of 1956 children (40% African‐American, 42% Hispanic, and 18% White) attending any 1 of 14 public elementary schools located in one large and one mid‐sized Midwestern city participated in this study. Peer ratings of victimization were obtained at two points in time, separated by a 2‐year period. Findings revealed that risk for being victimized by peers varied by ethnicity and by school context. Hispanic children had lower victimization scores than did either African‐American or White children. These findings, however, were moderated by school context, such that attending ethnically integrated schools was associated with a significantly higher risk of victimization for White children and a slightly lower risk of victimization for African‐American children and did not affect the risk of victimization for Hispanic children. In addition, African‐American children were less likely than Hispanic and White children to be repeatedly victimized by peers over time. The importance of considering ethnicity and context in explaining peer victimization is discussed and suggestions for preventive interventions and future research are provided.
Natural Disaster and Depression: A Prospective Investigation of Reactions to the 1993 Midwest Floods
Authors: Ginexi Elizabeth M. , Weihs Karen , Simmens Samuel J. , Hoyt Danny R. 
Published: December 2002

AbstractA statewide sample of 1735 Iowa residents, approximately half of whom were victims of the 1993 Midwest Floods, participated in interviews 1 year prior to, and 30 to 90 days after, the disaster. Employing a rigorous methodology including both control‐group comparisons and predisaster assessments, we performed a systematic evaluation of the disaster's impact. Overall, the disaster led to true but small rises in depressive symptoms and diagnoses 60–90 days postflood. The disaster–psychopathology effect was not moderated by predisaster depressive symptoms or diagnostically defined depression; rather, predisaster symptoms and diagnoses uniquely contributed to increases in postdisaster distress. However, increases in symptoms as a function of flood impact were slightly greater among respondents with the lowest incomes and among residents living in small rural communities, as opposed to on farms or in cities. Implications for individual‐ and community‐level disaster response are discussed.