bluuebunny/crossref_metadata_2025_split huggingface dataset:
Successful pregnancy outcome in a woman with argininosuccinate lyase deficiency
Authors: Mardach M. R. , Roe K. , Cederbaum S. D. 
Published: December 2002

AbstractArgininosuccinic aciduria (ASAD) is caused by deficiency of the fourth enzyme of the urea cycle, argininosuccinic acid lyase (EC 4.3.2.1; McKusick 207900). It results in the accumulation of large amounts of argininosuccinic acid in tissues and all the body fluids (Brusilow and Horwich 1995). The disorder may vary in severity from neonatal hyperammonaemia, which if untreated is fatal, to a biochemical abnormality without apparent clinical sequelae (Brusilow and Horwich 1995). A number of patients survive to adulthood and an increasing number have normal or near normal intelligence (Brusilow and Horwich 1995). There are, however, few reports of pregnancy outcome in women affected with this condition. Those available suggest that the offspring may not be at risk for development delay (Ward et al 1990; Worthington et al 1996). We report here the birth of two children to a woman affected with this disorder. Both were entirely normal developmentally as judged by formal testing. It supports the notion that this condition may not be embryotoxic due either to the inherent nontoxic nature of argininosuccinate or to its failure to cross the placenta in adequate amounts.
Benefits of normalizing plasma phenylalanine: Impact on behaviour and health. A case report
Authors: Williams K. 
Published: December 2002

AbstractAn elderly man with mental retardation who had never received dietary treatment for his phenylketonuria was placed on a phenylalanine‐restricted diet. Social skills and walking gait improved and a new interest in the objects in his environment developed spontaneously. A 2‐year analysis of diet, blood plasma phenylalanine levels and behavioural state indicated that small differences in phenylalanine intake impacted his well‐being. Of significant note, leg tremor and spasm that precipitated severe self‐injury were only reversible when plasma blood phenylalanine concentrations were titrated to near normal ranges and daily phenylalanine intake was strictly controlled. This case may offer a potential explanation for some of the late treatment failures that have been reported and suggest new avenues to explore in the late treatment of PKU.
Holocarboxylase synthetase deficiency: Report of a case with onset in late infancy
Authors: Touma E. , Suormala T. , Baumgartner E. R. , Gerbaka B. , Ogier de Baulny H. , Loiselet J. 
Published: December 2002

AbstractA case of holocarboxylase synthetase (HCS) deficiency of late‐infantile onset is presented and compared with the common manifestations in previously reported patients. Our patient had her first episode at 20 months followed by recurrent episodes of metabolic acidosis with ketolactic acidosis responding dramatically to a short trial of biotin and thiamin. The main clinical findings were metabolic acidosis with alteration in consciousness and respiration, which are in accordance with findings in earlier reported patients with both neonatal‐onset and infantile‐onset forms of HCS deficiency. The diagnosis of HCS deficiency was made only at the age of 5.5 years during a metabolic work‐up when organic acid analysis was performed. This revealed elevated urinary excretion of the characteristic metabolites, 3‐hydroxypropionate, 3‐hydroxyisovalerate and methylcitrate, suggesting multiple carboxylase deficiency (MCD). MCD was demonstrated in fibroblasts of our patient, but only when the cells were grown in a medium with a very low biotin concentration of10−10mol/L. Kinetic studies of reactivation of deficient propionyl‐CoA carboxylase activity with biotin in intact fibroblasts revealed a mildly decreased reactivation rate and only a 3–5 times higher biotin requirement as compared with controls. These findings are in accordance with a mild form of HCS deficiency.This child responded to 10mg/day of biotin with normal lymphocyte carboxylase activities and adequate school performance at 10 years of age.
Transport of phytanic acid on lipoproteins in Refsum disease
Authors: Wierzbicki A. S. , Sankaralingam A. , Lumb P. J. , Hardman T. C. , Sidey M. C. , Gibberd F. B. 
Published: December 2002

AbstractPatients with Refsum disease accumulate significant quantities of phytanic acid in adipose and neural tissue. The accumulation can be reversed by following a diet low in phytanic acid, yet the mechanism of transport of this fatty acid is obscure. We investigated the distribution of phytanic acid in different lipoprotein subfractions in 11 patients with Refsum disease and 9 unaffected siblings. Plasma phytanic acid was distributed on VLDL (16.2%±12.2%), IDL (1.77%±1.64%), LDL (34.8%±12.6%) and HDL (14.3%±7.87%). No correlations with any parameter were seen with total phytanic acid content. Weak nonsignificant correlations were found with the fractional distribution of phytanic acid and VLDL triglyceride (r=0.35; p=0.12) and plasma HDL‐cholesterol (r=0.32; p=0.16) and with LDL:HDL cholesterol ratio (r=0.33; p=0.14). Significant correlation of the fractional distribution of phytanic acid on lipoprotein particles was noted with the ratio of apolipoprotein B:apolipoprotein A1‐containing particles (r=0.46; p=0.03) and apolipoprotein B:apolipoprotein A1 in HDL2 (r=0.53; p=0.01). This suggests that the import–export balance for phytanic acid in plasma is related to forward and reverse cholesterol transport on lipoprotein particles, and only weakly to plasma cholesterol and triglycerides. These ratios of apolipoprotein particles may play a significant role in determining the rate of phytanic acid elimination in patients with Refsum disease.
Novel mutations in patients with fructose‐1,6‐bisphosphatase deficiency
Authors: Herzog B. , Wendel U. , Morris A. A. M. , Eschrich K. 
Published: December 2002

AbstractFructose‐1,6‐bisphosphatase (FBPase) deficiency is an autosomal recessive disorder of gluconeogenesis. Mutations have recently been identified in Japanese patients but none has been reported in patients of other ethnic backgrounds. We have undertaken sequence analysis on genomic DNA isolated from leukocytes of four patients with FBPase deficiency. Homozygous mutations were found in all four cases. One patient was homozygous for the common mutation identified in Japanese patients (960‐961insG in exon 7). The other three patients were all homozygous for novel mutations (35delA in exon 1, 778G→A in exon 6 and 966delC in exon 7). Normal and mutant FBPases were expressed in prokaryotic (E. coli TG2) and eukaryotic (COS1) cells. In cell‐free extracts the mutant proteins were enzymatically inactive, indicating that the mutations are responsible for the disease. In one affected family, molecular genetic analysis allowed the diagnosis to be excluded promptly in a newborn child 3 days after birth.
Biochemical monitoring of treatment for galactosaemia: Biological variability in metabolite concentrations
Authors: Hutcheson A. C. J. , Murdoch‐Davis C. , Green A. , Preece M. A. , Allen J. , Holton J. B. , Rylance G. 
Published: December 2002

AbstractRed cell galactose 1‐phosphate (Gal‐1‐P) concentrations and urinary galactitol excretion have been suggested as biochemical indices of dietary compliance in classical transferase‐deficient galactosaemia. We report our experience of measuring both in 32 patients over 0–10.9 years (median 3.45). A total of 438 blood specimens for Gal‐1‐P and 383 urine specimens for galactitol assay were received; 317 pairs of specimens were collected at the same time. Concentrations of both analytes fell rapidly over the first 2–3 months following dietary intervention, to mean (geometric SD) levels of 225 (1.60) μmol/L red cells for Gal‐1‐P and 388 (1.19) μmol/mmol creatinine for galactitol. Concentrations then fell exponentially over the next 7–8 years, with times to half‐disappearance of 6.3 years for Gal‐1‐P and 6.4 years for galactitol, to levels of 104 (1.58) and 193 (1.36) respectively in patients aged over 10 years. Concentrations of both analytes were independent of the presence of the common Q188R mutation. Mean intra‐ and inter‐individual coefficients of variation (CV) across the range of values studied were 36% and 61% for Gal‐1‐P, and 37% and 42% for galactitol. Analytical CVs were 3.6% for Gal‐1‐P and 5.5% for galactitol, indicating that the major source of variability is biological. The correlation coefficient between Gal‐1‐P and galactitol in paired samples overall was 0.33; the regression equation being [Galactitol] = 0.84[Gal‐1‐P]+176. Serial measurements of both Gal‐1‐P and galactitol may be valuable in monitoring galactosaemia, but high intra‐individual biological variability limits their usefulness. Standardization of sample collection times may improve this. Further work is needed to assess the predictive values of both analytes for long‐term outcome.
Disorders of mitochondrial fatty acyl‐CoA β‐oxidation
Authors: Wanders R. J. A. , Vreken P. , den Boer M. E. J. , Wijburg F. A. , Van Gennip A. H. , IJlst L. 
Published: December 2002

AbstractIn recent years tremendous progress has been made with respect to the enzymology of the mitochondrial fatty acid β‐oxidation machinery and defects therein. Firstly, a number of new mitochondrial β‐oxidation enzymes have been identified, including very‐long‐chain acyl‐CoA dehydrogenase (VLCAD) and mitochondrial trifunctional protein (MTP). Secondly, the introduction of tandem MS for the analysis of plasma acylcarnitines has greatly facilitated the identification of patients with a defect in fatty acid oxidation (FAO). These two developments explain why the number of defined FAO disorders has increased dramatically, making FAO disorders the most rapidly growing group of inborn errors of metabolism. In this review we describe the current state of knowledge of the enzymes involved in the mitochondrial oxidation of straight‐chain, branched‐chain and (poly)unsaturated fatty acyl‐CoAs as well as disorders of fatty acid oxidation. The laboratory diagnosis of these disorders is described, with particular emphasis on the methods used to identify the underlying enzyme defect and the molecular mutations. In addition, a simple flowchart is presented as a guide to the identification of mitochondrial FAO‐disorders. Finally, treatment strategies are discussed briefly.
Long‐chain 3‐hydroxyacyl‐CoA dehydrogenase deficiency: Variable expressivity of maternal illness during pregnancy and unusual presentation with infantile cholestasis and hypocalcaemia
Authors: Ibdah J. A. , Dasouki M. J. , Strauss A. W. 
Published: December 2002

AbstractPatients with long‐chain 3‐hydroxyacyl‐CoA dehydrogenase (LCHAD) deficiency present with a Reye‐like syndrome, cardiomyopathy, or sudden unexpected death. We describe an unusual presentation in a patient with unsuspected LCHAD deficiency. The proband presented at 2 months of age with an acute infantile hypocalcaemia and vitamin D deficiency associated with occult, unexplained cholestatic liver disease. Sudden, unexpected death occurred at 8 months. Molecular analysis revealed homozygosity for the prevalent LCHAD (1528G>C, E474Q) mutation. The mother had pre‐eclampsia during the third trimester of her pregnancy. In a subsequent pregnancy, she developed severe acute fatty liver of pregnancy (AFLP) and intrauterine fetal death at 33 weeks of gestation. In conclusion, infantile hypocalcaemia is an unusual phenotype associated with LCHAD deficiency. The maternal pregnancy history documents that fetal LCHAD deficiency is associated with a spectrum of maternal illnesses ranging from pre‐eclampsia to life‐threatening AFLP.
Automated mutation analysis
Authors: Ravine D. 
Published: December 2002

AbstractAutomated mutation analysis brings with it a vastly increased capacity in the number of test samples that can be processed at a time, as well as much improved test reproducibility. Until now, the introduction of automation into this field had been restricted to the use of semiautomated sequencing systems to make the most of the sequence information extractable from a single lane in an electrophoretic gel or in a polymer‐filled glass capillary. Much effort is now being directed into harnessing the potential of DNA microarrays (DNA chips) and there is increasing interest in the potential of matrix‐assisted mass spectrometry for determining the detail of large nucleic acid molecules. Meanwhile, there are other important recent developments already available, including robotic workstations, the further development of the allele‐specific oligonucleotide assay into microtitre formats, and its use with fluorescence for real‐time quantitative PCR analysis. Implementation of these developments in appropriate settings can further streamline the routine of molecular diagnostic laboratories, allowing them to take greater advantage of the recent surge of gene discoveries and their associated disease‐causing mutations.
Long‐term follow‐up following bone marrow transplantation for Hunter disease
Authors: Vellodi A. , Young E. , Cooper A. , Lidchi V. , Winchester B. , Wraith J. E. 
Published: December 2002

AbstractBone marrow transplantation (BMT) was performed in 10 patients with Hunter disease (mucopolysaccharidosis type II, iduronate‐2‐sulphatase deficiency). The donor was an HLA‐identical sibling in 2 cases, an HLA‐nonidentical relative in 6 cases, a volunteer unrelated donor in 1 case, and details were not available in 1 case. Only three patients have survived for more than 7 years post BMT; however, this high mortality probably resulted from poor donor selection. In two, there has been a steady progression of physical disability and mental handicap. One patient has maintained normal intellectual development, with only mild physical disability. It is possible that BMT may be useful in selected patients with MPS II.
Functional magnetic resonance imaging: Clinical applications and potential
Authors: Matthews P. M. , Clare S. , Adcock J. 
Published: December 2002

AbstractDemonstration that contrast in magnetic resonance images can be generated based on differences in blood oxygenation has led to an explosion of interest in so‐called functional magnetic resonance imaging (FMRI). FMRI can be used to map increases in blood flow that accompany local synaptic activity in the brain. The technique has proved remarkably sensitive and has been used to map a broad range of cognitive, motor and sensory processes in the brain entirely non‐invasively. More recently, efforts have been made to extend this technique to the analysis of clinical problems. A major application is for presurgical localization of cerebral functions, e.g. in the surgical treatment of epilepsy. The technique also is beginning to provide information on functional consequences of abnormal brain development. Perhaps most exciting are applications to neurological impairments that are not associated with structural abnormalities, such as learning problems, dyslexia and movement disorders. It is possible that useful applications of FMRI may be found for directly mapping sites of action of CNS‐active drugs. Although the extent of the potential clinical applications of this new brain mapping technique is not clear, the widespread availability of MRI scanners suggests that the technique should in some form soon become a routine tool in major neuroradiological centres.
Intermittent jaundice in patients with acute leukaemia: A common mutation of the bilirubin uridine‐diphosphate glucuronosyltransferase gene among Asians
Authors: Kimura T. , Akaba K. , Ikegami T. , Akiba K. , Kanazawa C. , Katsuura M. , Shimizu Y. , Imaizumi M. , Lin C. , Hayasaka K. 
Published: December 2002

AbstractThe Gly71Arg mutation of the hepatic bilirubin UDP glucuronosyltransferase (B‐UGT) gene associated with Gilbert syndrome prevails among Japanese and its gene frequency is 0.13. Among 20 patients with acute leukaemia, 4 patients showed intermittent unconjugated hyperbilirubinaemia during the course of combined chemotherapy. The Gly71Arg mutation was detected in all 4 patients with hyperbilirubinaemia, but was not found in 16 patients without hyperbilirubinaemia. Two of them were heterozygotes and one was a homozygote for the Gly71Arg mutation, and the other was a compound heterozygote of the Gly71Arg mutation and TA insertion mutation in the TATA box of the B‐UGT gene. In addition to the complications leading to hyperbilirubinaemia, including liver damage due to drugs, viral infections or tumour cell infiltrations and alloimmune haemolysis, carrier status for the Gly71Arg mutation should be considered in a patient with leukaemia showing intermittent hyperbilirubinaemia during the course of chemotherapy, especially among Japanese, Koreans and Chinese owing to its prevalence in those populations.
Single‐cell analysis of mitochondrial DNA in patients and a carrier of the tRNALeu(UUR) gene mutation
Authors: Saitoh S. , Momoi M. Y. , Yamagata T. , Nakauchi H. , Nihei K. , Fujii M. 
Published: December 2002

AbstractWe examined heteroplasmy of mutated mitochondrial DNA in single peripheral lymphocytes derived from 4 individuals carrying the nt 3243 A‐to‐G mutation, including two patients with MELAS, a patient with cardiomyopathy, deafness and diabetes mellitus, and the asymptomatic mother of one of the MELAS patients. In these subjects, all lymphocytes examined were heteroplasmic to different degrees, with a wider range of heteroplasmy evident in the symptomatic patients than in the healthy carrier.
Central nervous system involvement in gyrate atrophy of the choroid and retina with hyperornithinaemia
Authors: Valtonen M. , Näntö‐Salonen K. , Jääskeläinen S. , Heinänen K. , Alanen A. , Heinonen O. J. , Lundbom N. , Erkintalo M. , Simell O. 
Published: December 2002

AbstractIn gyrate atrophy of the choroid and retina with hyperornithinaemia (GA), a genetically determined deficiency of ornithine {3}d‐aminotransferase activity leads to high ornithine concentrations in body fluids. GA is characterized by centripetally progressing retinal and choroidal destruction and selective atrophy with tubular aggregates in type II skeletal muscle fibres. These findings have been suggested to be mediated by hyperornithinaemia‐induced deficiency of high‐energy creatine phosphate. As abnormal brain magnetic resonance images and electroencephalograms are found in another disorder of creatine metabolism, guanidinoacetate methyltransferase deficiency, we investigated the central nervous system involvement in GA, which seems to be associated with a milder degree of phosphocreatine deficiency. We compared 23 untreated GA patients with age‐matched healthy controls, and with 9 patients who had received creatine or creatine precursor supplementation daily for several years. The mean age of the patients (32±18 years) was similar to that of the controls (36±22 years). The MRI or EEG findings of the patients on creatine supplementation did not differ from those of the untreated group. Brain MRI revealed degenerative lesions in the white matter in 50% of the GA patients, and 70% of the patients had premature atrophic changes, with a striking increase in the number of Virchow's spaces. Of the patients whose EEG was recorded, 58% had abnormal slow background activity, focal lesions or high‐amplitude β rhythm (>50μV). The EEG findings were not associated with the MRI changes or with the age or the sex of the patients. Early degenerative and atrophic brain changes and abnormal EEG are thus features of GA, in addition to the well‐characterized eye and muscle manifestations.
Apolipoprotein E polymorphism and serum concentrations in patients with glycogen storage disease type Ia
Authors: Trioche P. , Francoual J. , Capel L. , Odièvre M. , Lindenbaum A. , Labrune P. 
Published: December 2002

AbstractIn patients with glycogen storage disease type Ia (glucose‐6‐phosphatase deficiency), serum triglyceride concentrations are markedly raised, whereas phospholipids and cholesterol levels are only moderately elevated. In addition, both VLDL and LDL lipoprotein fractions are raised. Despite these abnormalities, endothelial vascular dysfunction and atherosclerosis seem to be rare in such patients. In view of the crucial role of apolipoprotein E (apoE) in lipid metabolism, we studied both apoE polymorphism (40 patients) and serum concentration (20 patients) in patients with glycogen storage disease type Ia. The distribution of each allele at the apoE locus was similar to that reported in the general population, whereas serum apoE concentrations were raised in our patients. Raised apoE levels in the serum could play an important role in counterbalancing the at‐risk‐for‐atherosclerosis lipid profile of patients with glycogen storage disease type Ia. Moreover, E3 and E4 polymorphisms, predominant in our patients, have a high triglyceride binding capacity and are thus able to increase triglyceride clearance. However, the origin of raised concentrations of apoE is not completely clear though, bearing in mind previous reports regarding serum protein concentrations in such patients, increased hepatic synthesis is likely.
Congenital porto–left renal venous shunt as a cause of galactosaemia
Authors: Mizoguchi N. , Sakura N. , Ono H. , Naito K. , Hamakawa M. 
Published: December 2002

AbstractCongenital porto–left renal venous (PRV) shunt was found to be the cause of galactosaemia in four galactosaemic neonates detected by mass screening (Paigen method). The patients did not have hereditary galactosaemias and were diagnosed as having galactosaemia of unknown cause, because porto–systemic venous (PS) shunts had not been recognized. At the time of diagnosis, hypergalactosaemia was not severe (0.44–0.55 mmol/L; 8–10 mg/dl) and plasma concentration of total bile acids (TBA) did not suggest a PS shunt (46–50 μmol/L). However, slightly but consistently increased concentrations of galactose and TBA strongly suggested the presence of a PS shunt, and careful ultrasonographic investigation revealed PRV shunt. We conclude that PRV shunt should be suspected in patients with hypergalactosaemia of unknown cause.
The increased sensitivity of neurons with elevated glucocerebroside to neurotoxic agents can be reversed by imiglucerase
Authors: Pelled D. , Shogomori H. , Futerman A. H. 
Published: December 2002

AbstractWe have recently demonstrated that incubation of cultured rat hippocampal neurons with conduritol β‐epoxide (CBE), an inhibitor of glucocerebrosidase, the enzyme defective in Gaucher disease, results in changes in intracellular morphology and in functional calcium stores. Changes in levels of functional calcium stores are directly related to neuronal cell death. We now show that neurons incubated with either CBE or a non‐hydrolysable analogue of GlcCer (glucosylthioceramide), are more sensitive to the toxic effects of high concentrations of glutamate and of a variety of metabolic inhibitors. A linear relationship exists between level of accumulation of GlcCer and the extent of neuronal cell death. The deleterious effects of elevated GlcCer levels can be completely reversed by addition of human glucocerebrosidase (imiglucerase) to the culture medium. Imiglucerase is internalized to lysosomes, where it presumably degrades excess GlcCer. This suggests that the limited success of enzyme replacement therapy in neuronopathic forms of Gaucher disease is not due to lack of efficacy of glucocerebroside in degrading GlcCer in neurons of the central nervous system, and adds impetus to attempts to develop ways to efficiently deliver glucocerebrosidase to the brains of neurologically compromised Gaucher disease patients.