bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnosis in relationship to treatment of hyperphenylalaninaemia
Authors: Blaskovics M. E. 
Published: June 2005

AbstractPKU is not a single simply defined entity. It is part of a spectrum of the hyperphenylalaninaemias. Natural protein loading studies with uniform Phe equivalents are simple, and they are an inexpensive and safe way to determine or catagorize the types of hyperphenylalaninaemias (excluding defects of biopterin). Evidence from the US PKU Collaborative Study indicates that all patients with PKU do not require indefinite or prolonged restrictive dietary therapy to maintain normal intellectual functioning. Although there are as yet no absolute criteria, it appears that the milder forms of PKU may need treatment for a shorter period of time.
Problems related to diet management of maternal phenylketonuria
Authors: Acosta P. B. , Stepnick‐Gropper S. 
Published: June 2005

AbstractProvision of nutritionally complete elemental diets for pregnant women with PKU requires greater knowledge of ‘conditionally’ essential nutrient requirements than is presently available as well as application of known information. Formulation of elemental products needs to be improved to enhance aroma and taste and to decrease osmolality. Designers of the metal and vitamin components should keep in mind that a major portion (70–80%) of most of these nutrients must be obtained from the elemental products. Thus deletion of suspected essential minerals or vitamins could cause serious deficiencies. On the other hand, knowledge of appropriate ratios that make for improved trace metal absorption should be applied. Clinical nutritionists need to assist patients in selection of foods that are low in binding substances and provide ‘conditionally’ essential nutrients in adequate amounts. Closer cooperation between clinical nutritionists, nutrition scientists and food technologists should result in improved elemental products for care of pregnant women with PKU.
Presentation of the data of the Italian registry for oculocutaneous tyrosinaemia
Authors: Fois A. , Borgogni P. , Cioni M. , Molinelli M. , Frezzotti R. , Bardelli A. M. , Lasorella G. , Barberi L. , Durand P. , Di Rocco M. , Romano C. , Parini R. , Corbetta C. , Giovannini M. , Riva E. , Balato N. , Sartorio R. , Mollica F. , Zammarchi E. , Battini M. L. 
Published: June 2005

ConclusionsType II tyrosinaemia in Italy has no regional preponderance. Neuromotor retardation and/or microcephaly seem to be correlated with the higher values of tyrosine. Enzyme studies have been refused in all patients. Treatment with a low tyrosine diet has been successful when accepted: since in many patients the diagnosis was made rather late, it is not possible to evaluate the results of the diet for the prevention of neuromotor retardation.
Studies on the molecular defect in phenylketonuria and hyperphenylalaninaemia using antibodies against phenylalanine hydroxylase
Authors: Bartholomé K. , Dresel A. 
Published: June 2005

AbstractMonospecific antibodies against human phenylalanine hydroxylase were prepared. Liver extract of 10 patients with phenylketonuria (PKU) and of two patients with hyperphenylalaninaemia were examined for reactivity toward the antibodies in crossed immunoelectrophoresis. In all patients phenylalanine hydroxylase could be detected. In nine out of 10 patients with PKU the mutant enzyme did not differ from the wild type enzyme with respect to the electrophoretic mobility. In one case the mutant enzyme had a more negative charge. In the patients with hyperphenylalaninaemia the enzyme of one patient had normal electrophoretic mobility and the enzyme of the other differed from the normal enzyme. No difference could be shown in heterozygotes for PKU.
Turnover of the fast components of myelin and myelin proteins in experimental hyperphenylalaninaemia. Relevance to termination of dietary treatment in human phenylketonuria
Authors: Hommes F. A. , Eller A. G. , Taylor E. H. 
Published: June 2005

AbstractThe turnover of myelin and of myelin protein fractions has been measured in the central nervous system of rats who were placed on a hyperphenylalaninaemia‐inducing diet (3%L‐phenylalanine and 0.12%p‐chlorophenylalanine added to the normal laboratory chow) when they were 25 days of age. A considerably increased turnover of the fast component of myelin and of myelin protein fractions was observed, which was not found in weight‐matched controls or in controls fed the normal laboratory chow supplemented with 0.12%p‐chlorophenylalanine. The increased turnover is therefore due to the hyperphenylalaninaemic condition and not due to the slow‐down in growth or the presence ofp‐chlorophenylalanine. Furthermore, an inhibition of myelin synthesis due to the hyperphenylalaninaemic condition has been observed.Since these effects on myelin metabolism can be demonstrated to occur even when the brain has matured considerably, prudence should be exercised in considering the termination of the dietary treatment of patients with phenylketonuria.
Carrier detection in ornithine transcarbamylase deficiency
Authors: Haan E. A. , Danks D. M. , Grimes A. , Hoogenraad N. J. 
Published: June 2005

AbstractWe have studied six known heterozygotes for ornithine transcarbamylase (McKusick 31125; OTC) deficiency. All had abnormal results when tested by measurement of urine orotic acid after protein loading. Duodenal mucosa OTC assay detected fewer of the known heterozygotes but was a useful supplementary test. Urine orotic acid excretion after protein loading is influenced by age and results from women being tested must be compared with those from controls of appropriate age.
Decreased transport of ornithine across the inner mitochondrial membrane as a cause of hyperornithinaemia
Authors: Hommes F. A. , Ho C. K. , Roesel R. A. , Coryell M. E. , Gordon B. A. 
Published: June 2005

AbstractHyperornithinaemia due to a transport defect of ornithine across the inner mitochondrial membrane was demonstrated in three patients by measuring ornithine uptake by fibroblast mitochondria. Particulate compartments and soluble cytoplasm of fibroblasts were separated by a slight modification of the digitonin method of Zuurendonk and Tager. Patient's fibroblast pellet fraction contained significantly less radioactivity than control fibroblast pellet fraction after incubation of fibroblasts with [14C]‐ornithine. Since neither of the patients was deficient in ornithine‐δ‐oxoacid aminotransferase, we concluded that in these hyperornithinaemia patients a defect exists for transport of ornithine across the inner mitochondrial membrane. The exact nature of this transport defect remains to be elucidated.
Stimulation of ketogenesis by propionate in isolated rat hepatocytes: An explanation for ketosis associated with propionic acidaemia and methylmalonic acidaemia?
Authors: Rosario P. , Medina J. M. 
Published: June 2005

AbstractThe effect of propionate on ketone body production from oleate and octanoate in isolated rat hepatocytes was studied. Propionate (5 mmol/l) stimulated ketogenesis from oleate and octanoate, although the effect was more pronounced when octanoate was used as substrate. Propionate decreased CO2 production from fatty acids, suggesting that propionate inhibited the oxidation of free fatty acid carbons through the tricarboxylic acid cycle. Our results suggest that propionate enhanced ketogenesis as a consequence of the decrease in the rate of the tricarboxylic acid cycle, caused by propionate and/or its derivatives. The stimulation of ketogenesis caused by propionate is discussed as the possible cause of ketosis associated with propionic acidaemia and methylmalonic acidaemia.
Annotation Molecular genetics of methylenetetrahydrofolate reductase deficiency
Authors: Rozen R. 
Published: June 2005

SummaryIn severe MTHFR deficiency with neonatal or adolescent onset, 9 rare mutations have been identified. In mild MTHFR deficiency with thermolabile enzyme, a single common mutation (an alanine‐to‐valine substitution) is involved, but a genetic‐nutrient interactive effect is required to produce mild hyperhomocysteinaemia. This interactive effect has been proposed to be a risk factor for arteriosclerosis and for neural‐tube defects. Large‐scale studies are required for confirmation of the role of MTHFR in these multifactorial processes as well as to assess its role in other folate‐dependent disorders.
Haemostatic variables in phenylketonuric children under dietary treatment
Authors: Schulpis K. H. , Platokouki H. , Papakonstantinou E. D. , Adamtziki E. , Bargeliotis A. , Aronis S. 
Published: June 2005

SummaryClassical phenylketonuria (PKU) (McKusick 261600) is an inborn error of metabolism treated by a controlled low‐phenylalanine (Phe) diet started as soon as possible in the first days of life. Such a diet can be achieved with vegetable protein and can be considered non‐atherogenic because of the reduction of animal products. Thirty patients with PKU were classified into two groups according to their annual mean Phe levels. Their daily protein intake was largely replaced by PKU2 Milupa which contains a mixture of amino acids. The product has no phenylalanine or fat of any kind. Thirty‐eight (38) individuals of comparable age were used as controls. Group A (n=15) had good compliance with the special diet (Phe mean 192±115 µmol/L); group B (n=15) did not strictly adhere to the diet (Phe mean 595±263 µmol/L). Certain haemostatic components (factors I, VII, VIII, and X, antithrombin III, protein C, and plasminogen) and lipid variables (cholesterol, triglycerides, high‐density lipoprotein, low‐density lipoprotein, very‐low‐density lipoprotein) as well as Phe levels were estimated. All the haemostatic factors studied were found within the normal range with the exception of a significant reduction in protein C in both groups of PKU patients. Furthermore, a statistically significant reduction in factor VII and X concentrations was observed in patients on strict diet. Cholesterol and low‐density lipoprotein concentrations were significantly lower in PKU children compared to normal controls. It is suggested that even though the special diet of PKU children, especially in group A, is rich in vegetables, the reduced fat intake might have impaired the absorption of vitamin K and its delivery to the site of synthesis of vitamin K‐dependent haemostatic factors.
Removal of branched‐chain amino acids andα‐ketoisocaproate by haemofiltration and haemodiafiltration
Authors: Gouyon J. B. , Semama D. , Prévot A. , Desgres J. 
Published: June 2005

SummaryVenovenous haemofiltration (VVHF) and haemodiafiltration (VVHDF) were performed with a neonatal haemo(dia)filter (Miniflow 10, Hospal) on 8 anaesthetized rabbits infused with branched‐chain amino acids (leucine, isoleucine and valine) andα‐ketoisocaproate. The branched‐chain amino acids (BCAA) andα‐ketoisocaproate blood levels were close to those previously observed in neonates with maple syrup urine disease when extracorporeal blood purification was required. VVHF and VVHDF performances were assessed with two different blood flows ( and 16.6 ml/min). VVHDF was performed with four dialysate flow rates ( and 3.0 L/h).Within each period, clearances of the three BCAA were strictly similar. BCAA clearances obtained by VVHF were similar to ultrafiltration rates (respectively, 0.78±0.14 and 1.79±0.28 ml/min at high and low;p<0.05). Theα‐ketoisocaproate clearances obtained by VVHF were 0.39±0.17 and 0.92±0.43 ml/min at low and high (not significantly different).Whatever the value, the VVHDF procedures always allowed higher BCAA andα‐ketoisocaproate clearances as compared with the corresponding VVHF period with similar. BCAA clearances obtained by VVHDF with a 0.5 L/h dialysate flow were 4.1±0.5 and 5.4±0.5 mL/min at low and high, respectively. The concurrentα‐ketoisocaproate clearances were 2.5±0.8 and 2.9±1.0 ml/min.
Stable‐isotope selected‐ion monitoring quantification of methylmalonic acid in dried filter‐paper urine samples
Authors: Parnet J. M. , Divry P. , Vianey‐Saban C. , Mathieu M. 
Published: June 2005

SummaryUrea and creatinine were measured by Kodak Ektachem methods and methylmalonic acid by stable‐isotope gas chromatography—mass spectrometry in 24 urine samples from patients with methylmalonic acidaemia. For each sample analyses were performed both directly on the liquid urine and on an aliquot which had been blotted onto filter paper and dried. There was good correlation between the methylmalonate/creatinine ratios in liquid and dried urine (r2=0.983). Urine dried on filter paper can be used advantageously for monitoring treatment in patients with this disorder.
ALDP expression in fibroblasts of patients with X‐linked adrenoleukodystrophy
Authors: Kemp S. , Mooyer P. A. W. , Bolhuis P. A. , van Geel B. M. , Mandel J. L. , Barth P. G. , Aubourg P. , Wanders R. J. A. 
Published: June 2005

SummaryThe adrenoleukodystrophy gene encodes a peroxisomal integral membrane protein (ALDP) consisting of 745 amino acids with a molecular weight of 75 kDa. ALDP expression was studied in fibroblasts from 24 male ALD patients from 17 unrelated ALD kindreds. In four kindreds an identical 2‐base‐pair deletion was found. We report the absence of ALDP in 12 kindreds carrying nonsense mutations, frame shifts or amino acid substitutions in the carboxy terminus of ALDP, together accounting for 71% of the ALD kindreds. ALDP was present in five kindreds (29%) with amino acid substitutions in the amino terminal half of the protein; in two of these kindreds ALDP was present although at a reduced level. The absence of truncated proteins suggests that the carboxy terminus has a function in the stabilization of ALDP.
Phospholipids accumulation in mucolipidosis IV cultured fibroblasts
Authors: Bargal R. , Bach G. 
Published: June 2005

SummaryCultured fibroblasts from mucolipidosis IV patients accumulated phospholipids when compared to normal controls or cells from other genotypes. The major stored compounds were identified as phosphatidylcholine, phosphatidylethanolamine and to a larger extent lysophosphatidylcholine and lysobisphosphatidic acid. Pulse chase experiments of32P‐labelled phospholipids showed increased retention of these compounds in the mucolipidosis IV lines throughout the pulse and chase periods. Phospholipase A1, A2, C, D and lysophospholipase showed normal activity in the mucolipidosis IV lines and thus the metabolic cause for this storage remains to be identified.
Evidence for both endogenous and exogenous sources of the sphingomyelin storage in lymphoid cell lines from patients with Niemann‐Pick disease types A and B
Authors: Levade T. , Salvayre R. , Maret A. , Douste‐Blazy L. 
Published: June 2005

SummaryEpstein‐Barr virus‐transformed lymphoid cell lines from normal individuals and from patients with Niemann‐Pick disease types A, B or C were subjected to various culture conditions in order to study the source of the characteristic lysosomal storage of sphingomyelin observed in the tissues of Niemann‐Pick patients. The culture medium was supplemented with a serum substitute devoid of lipoproteins or with one of the following lipid sources: fetal calf serum, human low‐density lipoprotein (LDL), or human high‐density lipoprotein (HDL). Storage of sphingomyelin was demonstrated under all tested culture conditions in cells deficient in acid sphingomyelinase (Niemann‐Pick disease types A and B). In contrast, the sphingomyelin concentration in the lymphoid cell line from a Niemann‐Pick type C patient (not deficient in sphingomyelinase) was normal. After more than 30 days in a medium devoid of sphingomyelin, the Niemann‐Pick types A and B lymphoid cell lines showed accumulation of sphingomyelin about twice control. The concentration was higher when cells were grown in a medium supplemented with lipids, particularly human LDL or HDL. These results are consistent with the hypothesis that both exogenous and endogenous sphingomyelins participate in the lysosomal storage observed in lymphoid cell lines from patients with Niemann‐Pick disease types A and B.
Biochemical studies on prolidase in sera from control, patients with prolidase deficiency and their mother
Authors: Ohhashi T. , Ohno T. , Arata J. , Kodama H. 
Published: June 2005

SummaryProlidase activity in serum from normal subjects and the mother of two patients was readily detected without adding Mn2+ to the assay, and the activity was increased by addition of Mn2+ to the assay or preincubation with Mn2+. However, the activity in serum from patients with prolidase deficiency against gly‐pro, leu‐pro and val‐pro could not be detected irrespective of Mn2+ conditions and activity against met‐pro, ala‐pro and phe‐pro also showed a marked reduction compared to controls. Both normal and the patients' mother's prolidase activity against gly‐pro was reduced about 20% at 60°C compared to the activity at 37°C, but the addition of Mn2+ at 55°C increased the activity about 1.8‐fold, whereas prolidase activity of patients could not be increased by the addition of Mn2+. The addition of Co2+ increased prolidase activity in serum from control and the patients' mother but did not increase the heat stability. These results indicate that prolidase in serum from patients with prolidase deficiency is altered rather than markedly reduced in amount.
Abetalipoproteinaemia in adults: Role of vitamin therapy
Authors: MacGilchrist A. J. , Mills P. R. , Noble M. , Foulds W. S. , Simpson J. A. , Watkinson G. 
Published: June 2005

SummaryThe retinal and neurological complications of abetalipoproteinaemia may be preventable by replacing vitamins A and E from an early age, but their role in adult presentations is less clear. Two adult females with abetalipoproteinaemia have received 8 and 10 years respectively of replacement therapy with vitamins A, E and linoleic acid. In Case 1, visual function improved objectively on commencing therapy but has subsequently deteriorated and her neuropathy has slowly progressed. The rate of progression of neurological impairment in Case 2 was slowed but not halted by therapy, and her severe visual disturbance was unaffected. Replacement by fat soluble vitamins has only a limited role in the management of abetalipoproteinaemia once irreversible neurological/retinal damage has occurred.
Amniotic fluid glycoasparagines in fetal aspartylglycosaminuria
Authors: Mononen I. , Kaartinen V. , Mononen T. 
Published: June 2005

SummaryMidterm amniotic fluid samples from one pregnancy with the fetus affected by aspartylglycosaminuria and from 11 normal pregnancies were analysed for glycoasparagines accumulating in urine in aspartylglycosaminuria. The aspartylglucosamine concentration in the affected pregnancy was about five times higher than in the controls, but the absolute value was very low being only about one‐thousandth of that in urine in aspartylglycosaminuria and one‐tenth of that in urine samples from normal adults. In total monosaccharide analysis, only galactose content in the affected amniotic fluid was slightly elevated compared to controls, indicating that higher glycoasparagines typical of urine in aspartylglycosaminuria were not accumulated in significant amounts. The data demonstrate that the analysis of glycoasparagines in amniotic fluid is not likely to permit reliable prenatal diagnosis of aspartylglycosaminuria.
Fatal lactic acidosis due to deficiency of E1 component of the pyruvate dehydrogenase complex
Authors: Birch‐Machin M. A. , Shepherd I. M. , Solomon M. , Yeaman S. J. , Gardner‐Medwin D. , Sherratt H. S. A. , Lindsay J. G. , Aynsley‐Green A. , Turnbull D. M. 
Published: June 2005

SummaryPyruvate dehydrogenase complex deficiency is thought to be a common cause of lactic acidosis. We report a patient with lactic acidosis and intermittent weakness. The rate of oxidation of pyruvate by intact skeletal muscle and liver mitochondrial fractions was impaired and pyruvate dehydrogenase complex (PDC) activity was low. The amounts of immunoreactive dihydrolipoyl transacetylase and dihydrolipoyl dehydrogenase in liver and skeletal muscle mitochondrial fractions from the patient were normal. However, there were markedly lower concentrations of both theα andβ subunits of the E1 component of PDC.
Fifteen years' experience with 212 hyperammonaemic cases at a Metabolic Unit
Authors: Tokatli A. , Coşkun T. , Özalp İ 
Published: June 2005

SummaryTwo hundred and twelve cases with hyperammonaemia, diagnosed at the Metabolic Unit of Hacettepe Children's Hospital over the past 15 years, were evaluated both clinically and biochemically.
Allele‐specific amplification of genomic DNA for detection of deletion mutations: Identification of a French‐Canadian tay‐sachs mutation
Authors: Kaplan F. , Boulay B. , Bayleran J. , Hechtman P. 
Published: June 2005

SummaryA rapid and efficient method for the detection of a 7.6‐kb deletion in theβ‐hexosaminidase Aα‐subunit gene, a mutant allele causing Tay‐Sachs disease in French Canadians, is described. The protocol involves PCR (polymerase chain reaction) amplification of target sequences on normal and mutant chromosomes. Three amplification primers, a single 5′ primer complementary to normal and mutant DNA templates and two 3′ primers specific for normal and mutant DNA templates are required. The primers direct amplification of two unique fragments (normal and mutant) that are easily separated by gel electrophoresis. Allele‐specific oligonucleotide hybridization using normal and mutant probes to genomic DNA samples from normal, heterozygous and homozygous individuals confirms these results and is consistent with results of genotypic classification of individuals using Southern analysis. The method is applicable to detection of deletion mutations in cases where some deletion‐flanking sequence is known.
Type I hereditary tyrosinaemia: Presentation of 11 cases
Authors: Coşkun T. , Özalp İ. , Koçak N. , Yüce A. , Çaglar M. , Berger R. 
Published: June 2005

SummaryDiagnostic information is supplied for the early detection of subacute and chronic forms of type I tyrosinaemia.
Chronic inflammatory bowel disease in glycogen storage disease type 1B
Authors: Sanderson I. R. , Bisset W. M. , Milla P. J. , Leonard J. V. 
Published: June 2005

SummaryTwo children with glycogen storage disease type 1B developed chronic inflammatory bowel disease. The first, a 7‐year‐old boy, had ileitis and later developed perianal disease. The second developed colitis by the age of 9 years; in both the features were consistent with Crohn disease. The children had neutropenia and neutrophil mobility defects characteristic of GSD‐1B. It is suggested that these neutrophil abnormalities are important in the pathogenesis of the bowel inflammation.
Primary hyperoxaluria type I: Ultrastructural observations in liver biopsies
Authors: Iancu T. C. , Danpure C. J. 
Published: June 2005

SummaryThe liver ultrastructure of four patients with the peroxisomal disease primary hyperoxaluria type I has been investigated. In all cases, peroxisomes of normal appearance were present in the parenchymal cells, except that they were somewhat reduced in number and size. In all patients, conspicuous lipofuscin was present, presumably resulting from the various metabolic disturbances to which the livers were subjected during the course of their disease. Considerable hepatocyte iron overloading was found in the three patients who had been haemodialysed and/or had blood transfusion. Whether the relatively mild peroxisomal abnormalities (as compared to other peroxisomal diseases, such as Zellweger's syndrome) found in these hyperoxaluric patients are related directly to the peroxisomal deficiency of alanine:glyoxylate aminotransferase, or whether they are a secondary phenomenon, resulting from the consequent metabolic disturbance, remains to be elucidated.