bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolism of3H‐dehydroepiandrosterone sulphate by subjects with steroid sulphatase deficiency
Authors: Bergner E. A. , Shapiro L. J. 
Published: June 2005

SummaryPatients with steroid sulphatase deficiency develop ichthyosis with accumulation of cholesterol sulphate in plasma and in the stratum corneum. The present study was undertaken to determine whether desulphation of the C19 steroid DHEAS is also impaired. The mean plasma concentrations of DHEA and androstenedione were significantly lower for patients than for controls (p<0.02 and 0.001) while the mean concentration of DHEAS was higher (p<0.002). Following intravenous administration of3H‐DHEAS, one patient failed to desulphate3H‐DHEAS as evidenced by an absence of urinary3H‐glucuronides. A second produced normal amounts of urinary3H‐glucuronides (indicative of desulphation capacity) in a baseline study but did not desulphate3H‐DHEAS following ampicillin treatment to alter gut microflora. A third patient had consistent sulphatase activity with and without ampicillin.
Pattern reversal visual evoked potentials in phenylketonuria
Authors: Giovannini M. , Valsasina R. , Villani R. , Ducati A. , Riva E. , Landi A. , Longhi R. 
Published: June 2005

SummaryThe pathogenesis of brain dysfunction in phenylketonuria (PKU) is still under investigation. Hyperphenylalaninaemia results in increased turnover of myelin. In order to demonstrate the derangement of myelinization in PKU we studied the visual evoked potentials (VEP) in 14 PKU patients and in 20 normal subjects. VEP findings were correlated with the metabolic control of the disease and with the electroencephalographic findings. VEP were more sensitive than the EEG in detecting a neurological dysfunction. VEP are influenced by dietary control and are normal only in children with good metabolic control.
Dyggve‐Melchior‐Clausen syndrome with increased pipecolic acid in plasma and urine
Authors: Roesel R. A. , Carroll J. E. , Rizzo W. B. , van der Zalm T. , Hahn D. A. 
Published: June 2005

SummaryA child with the Dyggve‐Melchior‐Clausen syndrome associated with elevated pipecolic acid levels in plasma and urine is described. Other studies of peroxisomal function, including phytanic acid, very long‐chain fatty acids, and plasmalogen synthesis, were normal. This disorder may represent an incompletely characterized defect in peroxisomal metabolism.
Genetic expression of Menkes disease in cultured astrocytes of the macular mouse
Authors: Kodama H. , Meguro Y. , Abe T. , Rayner M. H. , Suzuki K. T. , Kobayashi S. , Nishimura M. 
Published: June 2005

SummaryThe copper concentration was investigated in the cultured astrocytes from macular mice, an animal model of Menkes disease. An excessive amount of copper was accumulated in the astrocytes as copper‐metallothionein. These results show that the underlying genetic defect of the macular mouse is expressed in the astrocytes. A similar situation may exist in Menkes disease and cause a failure of copper transport to neurones.
Worldwide survey of neonatal screening for biotinidase deficiency
Authors: Wolf B. 
Published: June 2005

SummaryNeonatal screening for biotinidase deficiency has been conducted in 14 countries since 1984. To 31 December 1990, 8 532 617 newborns were screened. One hundred and forty‐two infants with biotinidase deficiency were identified; 76 infants with profound deficiency (<10% of mean normal serum activity) and 66 infants with partial deficiency (10–30% of mean normal activity). The estimated incidence of profound biotinidase deficiency is 1:112 271 (1:85 000 to 1:145 000; 95% confidence limits) and the incidence of partial deficiency is 1:129 282 (1:112 700 to 1:177 000). The incidence of combined profound and partial deficiency is 1:60 089 newborns (1:49 500 to 1:73 100). The estimated frequency of the allele for biotinidase deficiency is 0.004 and an estimated 1 in 123 individuals is heterozygous for the disorder.
Neonatal screening for biotinidase deficiency in East‐Hungary
Authors: Havass Z. 
Published: June 2005

SummaryThere are two types of multiple carboxylase deficiency, the neonatal form with holocarboxylase synthetase defect and the late‐onset form with biotinidase deficiency. We report our preliminary experiences in screening for biotinidase deficiency. In total 43 493 infants were screened for the deficiency of the enzyme biotinidase; 0.14% false positive results that necessitated requests for second blood samples and two newborns with a biotinidase defect were identified during our pilot study. The definitive diagnosis required the demonstration of enzyme deficiency in serum. Both of the patients have residual biotinidase activity: 3.59% and 7.55%. These two newborns with biotinidase deficiency are treated with daily supplementation of free biotin. According to our preliminary results biotinidase deficiency satisfies all the criteria for incorporation into the national newborn mass screening.
Combined xanthine and sulphite oxidase defect due to a deficiency of molybdenum cofactor
Authors: Roesel R. A. , Bowyer F. , Blankenship P. R. , Hommes F. A. 
Published: June 2005

AbstractIncreased urinary excretion of xanthine, hypoxanthine, sulphite, thiosulphate and decreased serum uric acid were observed in an infant with profound failure to thrive. Other clinical findings included refractory seizures, spastic quadriplegia and profound psychomotor retardation. The patient died at 20 months of age. There were no detectable activities for xanthine oxidase and sulphite oxidase in the postmortem liver. Urothione, which is the metabolic excretory product of the molybdenum cofactor for molybdoenzymes was not present in the urine. A deficiency of the molybdenum cofactor which is common to both xanthine and sulphite oxidase is presumed to be the metabolic defect responsible for the absent activities of both enzymes.
Identification of cystic fibrosis homozygotes and heterozygotes by isoelectric focussing of serum proteins
Authors: Getliffe K. A. , Ward L. C. , Shepherd R. W. 
Published: June 2005

AbstractScreening of 44 cystic fibrosis homozygotes, 17 heterozygotes and 36 normal controls, by identification of cystic fibrosis protein (CFP), was performed on sera using an improved isoelectric focussing technique. CFP was observed in 91% of homozygotes, 88% of heterozygotes and 8% of normal controls tested. Partial purification of CFP by chromatofocussing indicates that CFP has a molecular weight of about 52000u. It is speculated that CFP is a normal serum protein that exhibits a quantitative difference in concentration between CF homozygotes, heterozygotes and normals.
Phosphoglycerate kinase: Studies on normal and a mutant human enzyme
Authors: Svirklys L. G. , Lee C. S. , O'Sullivan W. J. 
Published: June 2005

AbstractPhosphoglycerate kinase was purified from a number of tissues obtained at autopsy from a subject with the deficiency. Properties of the mutant enzyme were compared to those of PGK purified from tissue obtained from normal subjects. The purified enzyme from the propositus contained two components, a minor fraction (about 2–5%) which behaved similarly to the normal enzyme during the purification procedure, and a major fraction (>95%) which could not be purified by the same procedure. The major fraction demonstrated a number of other properties which differed from the normal. These included a tendency to form aggregates, increased heat sensitivity and altered nucleotide substrate specificity. The smaller fraction appeared to have effectively identical properties to that of the normal enzyme. In keeping with its X‐linked mode of inheritance, phosphoglycerate kinase from all normal tissues appeared to have identical kinetic properties, although evidence for minor variations, presumably due to post‐translational modifications, was obtained.
Clinical consequences of hyperlipidaemia
Authors: Thompson G. R. 
Published: June 2005

SummaryHyperlipidaemia is a common and important clinical entity which frequently has a genetic basis. The chief features of severe hypertriglyceridaemia are eruptive xanthomata and acute pancreatitis, whereas most forms of hypercholesterolaemia are associated with premature coronary heart disease. This applies especially to familial hypercholesterolaemia, which is also characterized by tendon xanthomata. Better recognition of hyperlipidaemia allied to recent improvements in treatment should help reduce the frequency of its disabling and sometimes fatal consequences.
Apolipoprotein polymorphism and multifactorial hyperlipidaemia
Authors: Utermann G. 
Published: June 2005

SummaryApolipoproteins AIV, B, E, and the Lp(a) glycoprotein are genetically polymorphic in humans. Three common allelesɛ2,ɛ2 andɛ4 control the polymorphism of apolipoprotein E. These code for proteins which differ in functional properties, e.g. receptor binding activity andin vivo catabolism. This explains the significant effect of the apoE gene locus on the variability of plasma lipoprotein concentrations and moreover the implication of apoE alleles in the aetiology of multifactorial forms of hyperlipidaemia e.g. familial type III hyperlipidaemia (apoE2; arg158→cys) and polygenic hypercholesterolaemia (apoE4; cys112→arg). A further gene locus controls the concentrations in plasma of the Lp(a) lipoprotein that is composed of an LDL‐like particle containing apoB‐100 and the disulphide‐bonded Lp(a) glycoprotein. The latter exhibits a genetic size polymorphism (MW∼400kD‐700kD) that is controlled by at least seven autosomal alleles. These alleles at the same time are involved in determining the plasma concentrations of the lipoprotein that range from <1 mg/dl to >200mg/dl. Thus there is evidence that genetic variability in apolipoproteins relates to the variability of lipoprotein concentrations in the population and is implicated in the aetiology of multifactorial hyperlipidaemias.
Strategy for the screening of tetrahydrobiopterin deficiency among hyperphenylalaninaemic patients: 15‐Years experience
Authors: Dhondt J. ‐L. 
Published: June 2005

SummaryTetrahydrobiopterin deficiency in hyperphenylalaninaemic babies has to be rapidly recognized since the disease requires a specific treatment. Based on 15 years experience, we report on the evolution of a strategy for the detection of such patients. A total of 913 hyperphenylalaninaemic patients have been studied and 15 tetrahydrobiopterin deficiences have been detected or confirmed.DHPR assay in dried blood samples and pteridine measurement in urine collected on filter paper combine convenient sampling and reliable tests for systematic investigation of hyperphenylalaninaemic patients for cofactor deficiency.
First trimester diagnosis of Inherited Metabolic Disease: Experience in the UK
Authors: Besley G. T. N. , Young E. P. , Fensom A. H. , Cooper A. 
Published: June 2005

SummaryExperience with first trimester diagnosis of inherited metabolic disease is still limited. In this report, data are collected from four major centres in the UK which provide a prenatal diagnosis service based on specific enzyme or gene product assay. The data were presented at a workshop on ‘First Trimester Diagnosis of Inherited Metabolic Disease’ held at the Institute of Child Health, London, on 21st June 1990.Approximately 100 different metabolic diseases can now be diagnosed in the first trimester, but because of the rarity of many of the disorders, experience of positive diagnoses, based on enzyme deficiency in fresh chorionic villus samples (CVS), cultured villus cells or early amniocentesis samples, is likely to be limited. It is, however, important that these results are reported and similarly that any problems which arise are fully documented.
Use of 4‐trifluoromethylumbelliferyl‐α‐l‐iduronide as a new substrate for detection of α‐l‐iduronidase deficiency in human tissues and for rapid prenatal diagnosis of Hurler disease
Authors: Tsvetkova I. V. , Karpova E. A. , Voznyi Y. V. , Zolotukhina T. V. , Biryukov V. V. , Semyachkina A. N. 
Published: June 2005

SummaryResults are presented of α‐l‐iduronidase assays in the leukocytes of normal individuals, patients with Hurler disease and heterozygous carriers. The assays were carried out using 4‐methylumbelliferyl‐α‐l‐iduronide and 4‐trifluoromethylumbelliferyl‐α‐l‐iduronide as substrates. It was shown that 4‐trifluoromethylumbelliferyl‐α‐l‐iduronide, along with the commonly used 4‐methylumbelliferyl‐α‐l‐iduronide, can serve as a specific substrate for α‐l‐iduronidase and is therefore suitable for demonstrating the enzyme deficiency in patients with Hurler disease, as well as the decrease of enzyme activity in heterozygous disease carriers. Using the two substrates a prenatal diagnosis of Hurler disease in a fetus was made on the basis of the lack of enzyme activity in amniotic fluid cell cultures. The diagnosis was confirmed by the results of α‐l‐iduronidase activity assay in fetal liver and kidney. It was found that 4‐trifluoromethylumbelliferyl‐α‐l‐iduronide is highly efficient for the rapid detection of α‐l‐iduronidase deficiency directly in pieces of tissues and in placenta, which is important for the prenatal diagnosis of Hurler disease.
Characterization of the mutations in three patients with pyruvate dehydrogenase E1α deficiency
Authors: Hansen L. L. , Brown G. K. , Kirby D. M. , Dahl H. ‐H. M. 
Published: June 2005

SummaryThe human pyruvate dehydrogenase complex catalyses the oxidative decarboxylation of pyruvate to acetyl‐CoA. Defects in several of the seven subunits have been reported, but the majority of mutations affect the E1 component and especially the E1α subunit. However, the clinical presentation of patients with pyruvate dehydrogenase E1α deficiency is extremely variable. Dependency of the brain on pyruvate dehydrogenase activity and localization of the gene for the somatic form of the pyruvate dehydrogenase E1α subunit to the X chromosome provide the basis for a better understanding of the variation in the clinical manifestations. Further understanding of the function and interaction of subunits and the pathophysiology of pyruvate dehydrogenase deficiency necessitates the characterization of mutations in the pyruvate dehydrogenase complex. We report the analysis of three patients with pyruvate dehydrogenase E1α deficiency. One female has a three base pair deletion which affects dephosphorylation of the subunit. Of two males analysed, one has a two base pair deletion causing a shift in the reading frame. The other has a base change, resulting in an Arg to His substitution. All three mutations are located near the carboxyl terminus of the subunit.
Acyl‐CoA oxidase, peroxisomal thiolase and dihydroxyacetone phosphate acyltransferase: Aberrant subcellular localization in Zellweger syndrome
Authors: van Roermund C. W. T. , Brul S. , Tager J. M. , Schutgens R. B. H. , Wanders R. J. A. 
Published: June 2005

SummaryWe have studied the presence and subcellular localization of peroxisomal 3‐oxoacylcoenzyme A thiolase, acylcoenzyme A oxidase and acyl‐CoA: dihydroxyacetonephosphate acyltransferase (DHAPAT) in fibroblasts from control subjects and patients with an inherited deficiency of peroxisomes (Zellweger syndrome), using immunofluorescence spectroscopy and density gradient centrifugation techniques. The results show that Zellweger cells contain unprocessed thiolase and unprocessed acyl‐CoA oxidase which are associated with structures containing a peroxisomal integral membrane protein of 69 kDa and having a density much lower than that of normal peroxisomes. The residual DHAPAT activity present in Zellweger cells is also contained in these structures. We conclude that these structures represent defectively assembled peroxisomes which may still be capable of importing some peroxisomal proteins.
Atypical riboflavin‐responsive glutaric aciduria, and deficient peroxisomal glutaryl‐CoA oxidase activity: a new peroxisomal disorder
Authors: Bennett M. J. , Pollitt R. J. , Goodman S. I. , Hale D. E. , Vamecq J. 
Published: June 2005

SummaryInvestigation of cultured skin fibroblasts in a patient with atypical riboflavin‐responsive glutaric acidura revealed a marked deficiency of peroxisomal glutaryl‐CoA oxidase. This is the first patient to be reported with glutaric aciduria caused by a peroxisomal rather than a mitochondrial dysfunction. This enzyme appears to be specific for glutaryl‐CoA, as lauryl‐CoA and dodecanedioyl‐CoA oxidase activities in the fibroblasts were both normal. The urinary excretion of glutaric acid (0.5 mmol mmol creatinine−1) suggests that the flux through this pathway is considerably less than the mitochondrial flux through glutaryl‐CoA dehydrogenase. The elevated glutaric acid excretion (to 0.8 mmol mmol creatinine−1) in response to lysine loading suggests that lysine is a precursor.
The pathogenesis of the Lesch‐Nyhan syndrome: ATP use is positively related to hypoxanthine supply to hypoxanthine guanine phosphoribosyltransferase
Authors: Harkness R. A. , McCreanor G. M. , Greenwood R. 
Published: June 2005

SummaryIn order to explain features of severe hypoxanthine guanine phosphoribosyltransferase (HPRT) deficiency, the Lesch‐Nyhan syndrome, a continuous supply of substrate, hypoxanthine, for the enzyme must be generated. This supply must be increased in association with increased ATP turnover.We have shown that ATP turnover continuously supplies hypoxanthine for recycling by the enzyme HPRT and that this supply increases curvilinearly with increasing ATP turnover. The effects of increasing exercise on ATP turnover were examined using a Latin square experimental design. The outputs of hypoxanthine, xanthine, urate and creatinine were measured. The data were then examined statistically.
2‐Deoxy‐d‐glucose uptake and fatty acid content in fibroblast cultures from children with syndromic paucity of interlobular bile ducts (alagille syndrome)
Authors: Couturier M. , Lemonnier F. 
Published: June 2005

Summary2‐Deoxy‐d‐glucose (2‐DOG) uptake was studied in skin fibroblast cultures from control children and children with Alagille syndrome or syndromic paucity of interlobular bile ducts (PILBD). No significant differences in uptake were observed between patients and controls. However, as the scatter of the results was larger in the fibroblasts from patients, we attempted to establish for these patients a relationship between 2‐DOG uptake and some biochemical parameters. We observed an inverse relationship between this uptake and the levels of plasma cholesterol and phospholipids (r=−0.85). Compared to controls, 2‐DOG uptake was significantly lower in cultures from patients who had very high levels of cholesterol (P2 group), but not in cultures from patients with moderately increased levels of cholesterol (P1 group). The level of total cellular cholesterol in cultured cells from the P1 and P2 groups was not significantly different from the control level, but we found marked differences between the concentrations of fatty acids. In the cultures from patients (especially the P2 group), we observed a significant increase in total fatty acids; among the saturated fatty acids, this increase chiefly concerned the 18:0 (14%) and among the polyunsaturated then −3 fatty acids (55%). The high concentrations of 20:5, 22:5 and 22:6, which enhance membrane fluidity, might explain the decrease in 2‐DOG uptake found in the cultures from patients (P2 group) with PILBD. The nature of these abnormalities might be connected with the genetic origin of Alagille syndrome
Normal vitamin requirements in neonates and infants
Authors: Bates C. J. 
Published: June 2005

AbstractInformation about vitamin requirements by neonates and infants has been derived from studies of the composition of breast milk, from feed‐response trials, from the occurrence of overt deficiency in infants fed damaged milk formulae, and by extrapolation from experimental deficiency studies on adult humans and on animals. Our knowledge is far from complete, however, and dietary recommendations have been formulated for only about half the known vitamins in the UK. In the near future, studies with stable isotope‐labelled vitamins should help to define pool sizes and turnover rates that are associated with particular intakes and thus give firmer evidence about requirements.
Intestinal transport of vitamins
Authors: Rose R. C. 
Published: June 2005

AbstractAnimals rely on acquiring through their diet, certain micronutrients required to support metabolism that we refer to as vitamins. The water‐soluble vitamins are absorbed in the intestine only slowly by simple diffusion; specific mechanisms of transport have evolved that normally insure complete availability of each substrate to the organism. Secondary genetic errors that result in the impairment of an intestinal transport mechanism may become debilitating.
Hyperphenylalaninaemia caused by defects in biopterin metabolism
Authors: Kaufman S. 
Published: June 2005

AbstractThe hepatic phenylalanine hydroxylating system consists of three essential components, phenylalanine hydroxylase, dihydropteridine reductase and the non‐protein coenzyme, tetrahydrobiopterin. The reductase and the pterin coenzyme are also essential components of the tyrosine and tryptophan hydroxylating systems. Recent studies have shown that there are three distinct forms of phenylketonuria or hyperphenylalaninaemia, each caused by the lack of one of these essential components. The variant forms of the disease that are caused by the lack of dihydropteridine reductase or tetrahydrobiopterin are characterized by severe neurological deterioration, impaired functioning of tyrosine and tryptophan hydroxylases and the resultant deficiency of tyrosine‐ and tryptophan‐derived monoamine neurotransmitters in brain.
Differential diagnosis of tetrahydrobiopterin deficiency
Authors: Niederwieser A. , Ponzone A. , Curtius H. ‐Ch. 
Published: June 2005

AbstractSix hundred and seventy‐three children (483 newborns and 190 older selected children) were screened for tetrahydrobiopterin (BH4) deficiency by HPLC of urine pterins and BH4 load test. One patient with GTP cyclohydrolase I deficiency, 36 patients with dihydrobiopterin synthetase (DHBS) deficiency (of which six were in the newborn and 30 in the older children) and 14 with dihydropteridine reductase deficiency (DHPR) were found. All 37 patients with defective BH4 biosynthesis responded to a BH4 load by lowering of the elevated serum phenylalanine concentration but four of 14 patients with DHPR deficiency did not. Measurement of DHPR activity in blood spots on Guthrie cards is recommended. Since subvariants of patients with BH4 deficiency exist, homovanillic acid, 5‐hydroxyindole acetic acid, pterins, phenylalanine, and tyrosine in cerebrospinal fluid should be measured for diagnosis and the control of therapy. The activity of the phosphate‐eliminating enzyme (a key enzyme in BH4 biosynthesis and part of “DHBS”) was measured in human liver and activities of approx. 1 n U (mg protein)−1 were found. In the liver biopsy of a patient with DHBS deficiency no activity (less than 3% of controls) was demonstrated.
Enzyme studies in biotin‐responsive disorders
Authors: Bartlett K. , Ghneim H. K. , Stirk H. ‐J. , Wastell H. 
Published: June 2005

AbstractThere appear to be at least two underlying aetiologies for combined carboxylase deficiency; firstly, a failure of biotinylation of apocarboxylases due to a mutation of holocarboxylase synthetase (EC 6.3.4.10) which results in an enzyme with a highKm with respect to biotin and secondly, a failure of biotinylation due to a lowered availability of biotin due to biotinidase deficiency (EC 3.5.1.12). In both these disorders secondary defects of all four biotin‐dependent carboxylases result which in turn causes the excretion of the metabolites characteristic of the isolated carboxylase deficiencies. In addition, both disorders respond biochemically and clinically to the administration of large amounts of biotin.