bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma lipids and lipoproteins of a patient with cholesteryl ester storage disease
Authors: Kostner G. M. , Hadorn B. , Roscher A. , Zechner R. 
Published: June 2005

AbstractThe plasma lipids, lipoproteins and lipolytic enzymes of a patient suffering from cholesterol ester storage disease were investigated and followed over a time period of 3 years. The patient was hypertriglyceridacmic and cholesterolaemic and exhibited very low levels of high density lipoproteins. These lipoproteins consisted almost exclusively of the HDL‐subfraction‐3. Apolipoprotein‐B was elevated and apoAI and AII were grossly reduced. The activity of lipoprotein lipase was normal, but hepatic lipase values were increased. Lecithin : cholesterol acyltransferase was in the upper normal range. The corresponding lipoprotein and enzyme values of one brother were within normal limits but some components measured in the plasma of the father were abnormal. It is speculated that the low plasma HDL levels in this disease may be a consequence of increased hepatic lipase activity in addition to a derangement in the reverse cholesterol flow.
Persistent succinylacetone excretion after liver transplantation in a patient with hereditary tyrosinaemia type I
Authors: Tuchman M. , Freese D. K. , Sharp H. L. , Whitley C. B. , Ramnaraine M. L. , Ulstrom R. A. , Najarian J. S. , Ascher N. , Buist N. R. M. , Terry A. B. 
Published: June 2005

AbstractA liver transplant was performed on a 4‐year‐old female in liver failure caused by hereditary tyrosinaemia, with hepatocellular carcinoma following a negative evaluation for metastases. However, serum alpha‐fetoprotein levels never returned to normal after the surgery. Urinary succinylacetone (SA) was detected in her urine prior to transplantation despite strict adherence to a low‐tyrosine diet. Other patients with severe liver disease awaiting liver transplantation do not excrete SA in the urine. She continued to excrete SA during the postoperative period despite normal liver functions. Oral tyrosine loading resulted in significant elevation of SA excretion. Possible explanations for this observation and clinical and therapeutic relevance are discussed.
The glasgow register of congenital anomalies 1972–88: A critical review
Authors: Stone D. H. 
Published: June 2005

SummarySince 1972, the Glasgow Register of Congenital Anomalies has collected population‐based data on all anatomical, metabolic and genetic congenital anomalies. Multiple sources of ascertainment, with no time limit for registration, are used. Its objectives are the detection of epidemics, the calculation of prevalence rates, the epidemiological investigation of malformations and the study of cohorts of survivors. A review of the achievements of the Register to date suggests that these objectives have only partly been fulfilled, though a number of recent measures, including the association of the Register with the multi‐centre European Registry (EUROCAT), have improved its future prospects. Previously unpublished data on cystic fibrosis and phenylketonuria are presented indicating that the prevalence rates of these disorders are stable and comparable to those of other centres, while the prevalence of hypothyroidism appears to have risen slightly since 1982.
Transient neonatal tyrosinaemia
Authors: Rice D. N. , Houston I. B. , Lyon I. C. T. , Macarthur B. A. , Mullins P. R. , Veale A. M. O. , Guthrie R. 
Published: June 2005

SummaryChildren who had presented with transient neonatal tyrosinaemia (TNT) were compared with a group of unaffected controls at 7–9 years of age. A comprehensive psychometric assessment revealed significant differences between the groups in adaptive behaviour, psycholinguistic abilities, and speed of learning. In nearly all components of the tests used, higher levels of TNT were associated with lower levels of performance. This study demonstrates that TNT, a condition commonly regarded as benign in the short term, has long‐term effects which may be detrimental to the child in school.
Comparison between the formation and the oxidation of dicarboxylylcarnitine esters in rat liver and skeletal muscle: Possible implications for human inborn disorders of mitochondrialβ‐oxidation
Authors: Vamecq J. , Draye J. ‐P. 
Published: June 2005

SummaryThe activity of dicarboxylyl‐CoA synthetase previously reported in rat liver was detected, in the presence of added detergents, in rat skeletal muscle. In both tissues, carnitine dicarboxylyltransferase activities were recorded but their substrate chain length specificity was, however, different. In rat skeletal muscle, but not liver, a carnitine‐dependent oxidation by intact mitochondria of dodecanedioyl‐CoA was easily detected by the spectrophotometric measurement of the substrate‐dependent ferricyanide reduction.The implications of the present data for the pathogenesis of disorders with excess urine dicarboxylylcarnitine esters are discussed.
Trimethylaminuria: The detection of carriers using a trimethylamine load test
Authors: Al‐Waiz M. , Ayesh R. , Mitchell S. C. , Idle J. R. , Smith R. L. 
Published: June 2005

SummaryA method potentially of value for investigating putative heterozygotes or carriers of trimethylaminuria by using a single oral dose of trimethylamine (TMA) is described. For healthy volunteers under normal dietary condition and following oral challenge with 300 mg and 600 mg TMA‐base, over 90% of the urinary TMA was excreted in the form of TMA (93.6 ± 1.6%). However, at a dose level of 900 mg TMA‐base, there was clear evidence of saturation of theN‐oxidation reaction as urinary TMA excretion declined to 77.2% (range 74.8–78.9) of the total dose of TMA. By contrast, in pedigree studies based upon propositi with trimethylaminuria, several parents were identified who showed clear evidence of saturation of theN‐oxidation of TMA at the 600 mg TMA‐base dose level, but not at 300 mg TMA‐base or under normal dietary condition. In these individuals, the proportion of urinary TMA as trimethylamineN‐oxide (TMAO) declined to (77.3 ± 1.7%). Accordingly we propose that the oral administration of 600 mg TMA‐base and the analysis of the following 0–8‐h urine collection may be useful for the investigation of possible carriers of trimethylaminuria.
Fibroblast α‐galactosidase a activity for identification of Fabry's disease heterozygotes
Authors: Fensom A. H. , Benson P. F. , Grant A. Ronayne , Jacobs L. 
Published: June 2005

AbstractThe identification of female carriers of Fabry's disease is important for genetic counselling since prenatal diagnosis of affected fetuses is possible. The activities of either total α‐galactosidase or α‐galactosidase A in cultured fibroblasts were similar in Fabry carriers and controls and cannot therefore be used for carrier detection. Better discrimination between carriers and controls was found when total α‐galactosidase activity was expressed as a ratio to β‐galactosidase activity, but overlap still occurred. However, there was complete discrimination between the ratio of α‐galactosidase A to β‐galactosidase in cultured fibroblasts from five carriers of Fabry's disease and either 11 controls, seven hemizygote affected males or two of their female relatives.
Brain disorders in relation to biochemical lesions
Authors: Wilson J. 
Published: June 2005

ConclusionThe paediatric neurologist confronted with an array of named and unnamed heredo‐degenerative disorders, as yet undefined biochemically, is continually frustrated by the therapeutic nihilism and by genetic counselling based on a statistical estimate of risk. Regrettably, clinical observation has provided few clues so far with which to direct research, but since further technical innovation is unlikely to provide helpful answers unless the appropriate questions are asked, it is essential that we go on trying to formulate proper questions.
Neutropenia and impaired neutrophil function in glycogenosis type Ib
Authors: Di Rocco M. , Borrone C. , Dallegri F. , Frumento G. , Patrone F. 
Published: June 2005

AbstractThe impairment of different neutrophil functions has recently been reported in some patients with glycogenosis Ib and neutropenia. However, no satisfactory explanation for these findings has so far been supplied. In order to investigate this problem, we have studied neutrophil functions (random locomotion and chemotaxis, O2− release, [1‐14C]glucose oxidation and cellular cytotoxicity) in two further patients with glycogenosis Ib and neutropenia. The results show that neutrophil dysfunctions related to the involvement of both hexose monophosphate shunt and anaerobic glycolysis were variable. The heterogeneity of neutrophil functional impairment in glycogenosis Ib and their possible relationship with the basic metabolic defect of the disease are discussed.
The pH of mitochondria of fibroblasts from a hyperornithinaemia, hyperammonaemia, homocitrullinuria‐syndrome patient
Authors: Metoki K. , Hommes F. A. 
Published: June 2005

AbstractThe intracellular pH of control fibroblasts and of fibroblasts of a HHH‐syndrome patient have been determined. Values of 6.94±0.15 and 7.05±0.14 for control and patient fibroblasts, respectively, were found. By means of analyses of malate in the cytosolic and particulate fractions of the fibroblasts the differences in pH between these two cellular compartments were estimated to be 1.34±0.12 and 1.38±0.18 for control and patient, respectively. Neither difference was statistically significant. The decrease in the rate of ornithine uptake by mitochondria of the patient's fibroblast is therefore not due to an increased intramitochondrial pH.
Immune functions in methylmalonicaciduria
Authors: Church J. A. , Koch R. , Shaw K. N. F. , Nye C. A. , Donnell G. N. 
Published: June 2005

AbstractA variety of phagocytic cell and lymphocyte assays were employed to evaluate the immune status of four patients with methylmalonicaciduria. One patient had a depressed absolute granulocyte count and two patients had depressed neutrophil and monocyte chemotactic responses. All subjects had normal neutrophil phagocytic and bactericidal activities. One patient had a decreased T‐cell number; blastogenic responses to phytohaemagglutinin and pokeweed mitogen were normal in all subjects. B lymphocyte measurements were variably abnormal; two children had decreased B‐cell numbers; two had marginally decreased IgG levels; a third had an undetectable rubella titre; and two had elevated serum IgE concentrations.In vitro exposure of normal cells to methylmalonic acid concentrations up to 50mg/100 ml did not affect chemotactic or lymphoproliferative responses.In conclusion, although B‐cell function may be affected, no consistent abnormality of lymphocyte or phagocytic cell functions could be attributed to the metabolic disorder.
Congenital dislocation of the hip: A possible inborn error of collagen metabolism
Authors: Skirving A. P. , Sims T. J. , Bailey A. J. 
Published: June 2005

AbstractSignificant changes in the type of collagen, the fibril diameter and the nature of the crosslinks have been demonstrated in the joint capsules of subjects with congenital displacement of the hip (CDH). These changes are probably tissue specific since no detectable change could be observed in the skin of these subjects compared to controls. These preliminary biochemical studies clearly demonstrate that CDH involves an error in collagen metabolism.
Serum and hair zinc as predictors of clinical symptoms in acrodermatitis enteropathica
Authors: Anttila P. , Simell O. , Salmela S. , Vuori E. 
Published: June 2005

AbstractHair‐ and serum‐zinc concentrations were measured in six patients with acrodermatitis enteropathica before and sequentially after cessation of zinc supplementation; supplementation was restarted when symptoms appeared. Serum zinc correlated accurately with zinc dosage and was lowest when symptoms of deficiency appeared. Hair zinc was initially age‐ and body size‐related and was minimally influenced by the supplementation break. Adult patients had continuously normal concentrations. In paediatric patients hair zinc was low. Their serum concentrations should probably be maintained slightly above or at the upper limit of reference values for prolonged periods for normalization of hair and perhaps tissue zinc contents.
A sensitive semi‐automated kinetic assay of α‐D‐glucosidase for the prenatal diagnosis of type 2 glycogenosis (Pompe's disease)
Authors: Blau K. 
Published: June 2005

AbstractPrenatal diagnosis of type 2 glycogenosis (Pompe's disease) has been done on cultured amniotic fluid cells, using a semi‐automated fluorimetric kinetic assay for α‐D‐glucosidase with 4‐methylumbelliferyl‐α‐D‐glucoside as substrate. The activity of the enzyme was related to that ofβ‐D‐galactosidase, and found to be absent in cells from an affected fetus. The diagnosis was confirmed in fetal liver, where the same assay was used to show absence ofα‐D‐glucosidase activity with normalβ‐D‐galactosidase activity, and where increased glycogen deposition was demonstrated histologically. This type of assay is generally applicable to lysosomal enzymes, and to other fluorigenic enzyme reactions.
Deranged isoleucine metabolism during ketotic attacks in patients with methylmalonic acidaemia
Authors: Duran M. , Bruinvis L. , Ketting D. , Wadman S. K. 
Published: June 2005

AbstractTwo patients with methylmalonic acidaemia due to methylmalonyl‐CoA mutase deficiency were studied for several years. Both exhibited at least two attacks of severe ketoacidosis, during which they excreted, in addition to methylmalonic acid, a number of abnormal compounds: 3‐hydroxypropionic acid, 2‐methyl‐3‐hydroxybutyric acid, 3‐hydroxy‐n‐valeric acid, 3‐oxo‐n‐valeric acid, 2‐methyl‐3‐oxobutyric acid, citraconic acid andN‐tiglylglycine. These compounds represent partly intermediary metabolites from the isoleucine degradation pathway and partly secondary metabolites of propionyl‐CoA and tiglyl‐CoA.
A new patient with dicarboxylic aciduria suggestive of medium‐chain acyl‐CoA dehydrogenase deficiency presenting as Reye's syndrome
Authors: Del Valle J. A. , Garcia M. J. , Merinero B. , Pérez‐Cerdá C. , Roman F. , Jimenez A. , Ugarte M. , Martínez‐Pardo M. , Ludeña C. , Camarero C. , del Olmo R. , Duran M. , Wadman S. K. 
Published: June 2005

AbstractA new patient with medium‐chain dicarboxylic aciduria and suberyl glycinuria during an attack of acute illness is reported. When, inadvertently he was given medium‐chain triglycerides for 2 days, the excretion of abnormal metabolites of medium‐chain fatty acids increased and hepatomegaly became more pronounced. During remission a low excretion of the metabolites were observed. After 16 h of fasting hypoglycaemia was accompanied by an increase of urinary dicarboxylic acids and ψ‐hydroxyacids similar to that found on admission. Interestingly this urinary organic acid pattern persisted 8 h after intravenous administration of glucose. In a blood sample obtained after 16 h of fasting there was hypoketonaemia and increased levels of total free fatty acids, octanoic, decanoic andcis‐4‐decenoic acids. These biochemical data suggest the existence of a deficiency at the level of medium‐chain acyl‐CoA dehydrogenase.
Dihydropteridine reductase deficiency: Non‐response to oral tetrahydrobiopterin load test
Authors: Lipson A. , Yu J. , O'Halloran M. , Potter M. , Wilken B. 
Published: June 2005

AbstractIn a child with dihydropteridine reductase deficiency (McKusick 26163) none of four separate oral tetrahydrobiopterin loading tests resulted in a decrease of the serum phenylalanine concentration. This test cannot be recommended for screening hyperphenylalaninaemic patients for dihydropteridine reductase deficiency.
Paired comparisons between early treated PKU children and their matched sibling controls on intelligence and school achievement test results at eight years of age
Authors: Koch R. , Azen C. , Friedman E. G. , Williamson M. L. ,   Writing Committee for the PKU Collaborative Study
Published: June 2005

AbstractEarly‐treated PKU children were compared to their matched non‐PKU sibling controls on Wechsler Intelligence Scale for Children (WISC) and Wide Range Achievement Test (WRAT) results at age 8. Fifty‐five PKU children had mean WISC Full Scale IQ score of 100, in comparison to a mean of 107 for their matched sibling controls (p=0.001). Treatment parameters significantly correlated with sibling‐PKU IQ score differences included maximum diagnostic phe level (r=0.244,p=0.036) and phe levels at age 6 (r=0.329,p=0.007) and at age 8 (r=0.489,p<0.0005). Fifty PKU subjects scored significantly lower than their matched sibling controls on standard scores of the WRAT Reading (102 vs. 107,p=0.016) and Arithmetic (96 vs, 101,p=0.006) subtests, and lower, but not significantly so, in Spelling (100 vs. 103,p=0.145). When the sample was grouped according to diet status at age 8, on‐diet PKUs scored at or above the level achieved by their siblings on all three scales of the WISC and all three WRAT subtests, whereas the off‐diet group scored from 7 to 13 points below their siblings on all measures.These results suggest that PKU children should restrict phe intake at least through their school years.
Metallothionein — Aspects related to copper and zinc metabolism
Authors: Cousins R. J. 
Published: June 2005

AbstractMetallothionein is a cysteine‐rich, low molecular weight protein that binds zinc, copper and cadmium. It is inducible in liver, kidney and intestine by glucocorticoids, changes in the dietary zinc supply, acute administration of various metals, food restriction, infection, stress and endotoxin treatment. Regulation of synthesis involves altered gene expression. The protein is fairly rapidly degraded when zinc is the primary metal species bound, but the degradation rate is diminished when cadmium or copper are bound as well. The net result of metallothionein production seems to be accumulation of bound metal and/or intracellular metal redistribution. The accumulation of copper in various tissues of individuals with Menkes' and Wilson's diseases may be related to altered metallothionein turnover. The physiological function is not clear, but the response of metallothionein to hormonal stimuli is suggestive of an important role in cellular metabolism.
Hudson memorial lecture: Wilson's disease: Genetics and biochemistry—their relevance to therapy
Authors: Walshe J. M. 
Published: June 2005

AbstractWilson's disease is an inherited metabolic disorder affecting children, adolescents and young adults. Before puberty the initial signs and symptoms are almost always related to liver damage, with or without haemolysis. After puberty neurological signs become increasingly prominent, always involving the motor centres, sometimes personality, never the sensory nervous system. The most characteristic physical sign is the Kayser Fleischer corneal pigment ring resulting from deposition of copper in Descemet's membrane.The primary genetic defect is not known but the disease appears to result from a failure, by the hepatocytes, to excrete copper via the bile. As a result this metal accumulates first in the liver then, when this organ is saturated, in the brain, the corneae, and to a lesser extent the kidneys. Once present in excess in the tissues copper poisons various enzyme systems leading to cellular damage and death. At present there is no satisfactory explanation for the pleomorphic nature of the disease much less of the often gross assymetry of the lesions in the brain.Treatment entails the establishment of a negative copper balance until the abnormal body stores of the metal have been removed. Thereafter the patient must be kept in balance for life. There are two main drugs available for this purpose, penicillamine and triethylene tetramine (Trientine). Both will achieve biochemical and clinical reversal of the disease. Penicillamine can give rise to a wide range of toxic reactions, mostly on an immunological basis; it is therefore essential to monitor the blood count and renal function regularly. Less is known at present of the potential of Trientine to induce unwanted side effects.Wilson's disease is characterized by recessive inheritance. It can be diagnosed in the presymptomatic stage by finding typical abnormalities of copper metabolism. All families should be screened and, where appropriate, prophylactic treatment started, thus aborting the clinical evolution of the disease.
Iron and haemochromatosis
Authors: Worwood M. 
Published: June 2005

AbstractThere have recently been considerable advances in the understanding of the inheritance of idiopathic haemochromatosis (McKusick 23520). The disorder is determined by a locus closely linked to the HLA loci on the short arm of chromosome 6. There is a recessive mode of transmission. The gene frequency may be as high as 0.05 in some parts of the world. HLA typing makes it possible to identify family members who are homozygous for idiopathic haemochromatosis and measurement of transferrin saturation and serum ferritin concentration will identify those with iron overload. Treatment is by regular phlebotomy. Few advances have been made in the 50 years in the understanding of the abnormality which permits the increased absorption of iron and which causes the iron overload.
The role of peroxisomes in mammalian cellular metabolism
Authors: Lazarow P. B. 
Published: June 2005

AbstractPeroxisomes, which are widely distributed in mammalian tissues, carry out several important functions in cellular metabolism. Production of alkylglycerol‐3‐phosphate, a key intermediate in the synthesis of plasmalogens and other ether lipids, occurs in the peroxisome. A fatty acid β‐oxidation system with significant differences from mitochondrial β‐oxidation is also found in the peroxisomes; the acetyl‐CoA produced is used for synthetic reactions. This pathway has a particularly important physiological role in the oxidation of very long chain fatty acids and the side chain of cholesterol. Peroxisomes also possess a number of oxidases that produce H2O2 which is decomposed by peroxisomal catalase. The function of this peroxisomal respiratory pathway is disposal of excess reducing equivalents, protection of the cell against H2O2 and possibly a role in thermogenesis in brown adipose tissue. Other peroxisomal functions include a role in gluconeogenesis and in purine and polyamine catabolism. Some enzymes of peroxisomes can be induced by dietary, hormonal and other physiological changes. The entire organelle proliferates under certain of these conditions.
Biogenesis of mitochondria and genetics of mitochondrial defects
Authors: Kroon A. M. , Van den Bogert C. 
Published: June 2005

AbstractMitochondria are formed by the concerted action of two genetic systems: the nucleocytoplasmic system and the intrinsic mitochondrial system. The genetic contribution of the mitochondria is modest because the genetic potential of mtDNA of mammals is restricted to the equivalent of about 16 000 base pairs. For various animals and man the complete base sequence of mtDNA is known and all possible polypeptide genes have now been assigned to subunits of the respiratory enzymes. The mtDNA sequences are not present on the nuclear genome.From a genetic point of view it is important that the inheritance of mtDNA is strictly maternal. Mutations of mtDNA primarily lead to impairments of energy metabolism. In view of the indispensability of oxidative phosphorylation for obligatory aerobic organisms, such mutations should be lethal. However, there are various inborn errors of metabolism with tissue‐specific manifestations, which are maternally inherited. The question discussed is whether these diseases can be explained on the basis of mutations of mitochondrial gene products. Tissue specificity poses a special problem, since it is not very attractive to assume that there is a heterogenous population of mtDNA molecules in the fertilized egg. Therefore, one should rather think in terms of a double mutational event, one tissue‐specific cytoplasmic and the other general mitochondrial. These mutations only give rise to metabolic disturbances if they are expressed together in the same cell.