bluuebunny/crossref_metadata_2025_split huggingface dataset:
A D255H substitution in the arylsulphatase A gene of two unrelated Belgian patients with late‐infantile metachromatic leukodystrophy
Authors: Lissens W. , Vervoort R. , Van Regemorter N. , Van Bogaert P. , Freund M. , Verellen‐Dumoulin C. , Seneca S. , Liebaers I. 
Published: June 2005

SummaryMetachromatic leukodystrophy (MLD) is an autosomal recessive disease of myelin metabolism caused by a deficiency in the lysosomal enzyme arylsulphatase A (ARSA). We have identified a new mutation in exon 4 of the ARSA gene of two unrelated Belgian patients with late‐infantile MLD. The mutation predicts an aspartic acid‐to‐histidine substitution at position 255 in arylsulphatase A (D255H), in a highly conserved region among sulphatases. Transient expression of the mutation in COS cells did not show an increase in ARSA activity. Both patients were compound heterozygotes carrying the frequent splice site mutation in intron 2 (459+1G→A) on the other allele.
The effect of ethanol on glucose production in phosphorylase b kinase deficiency
Authors: Collins J. E. , Bartlett K. , Leonard J. V. , Aynsley‐Green A. 
Published: June 2005

SummaryGlucose production was measured using stable isotopic techniques in two patients with phosphorylase b kinase deficiency before and after oral ethanol (0.75 g/kg). Glucose production was normal before the ethanol. In one patient, who did not take the full dose of ethanol, glucose production rose initially and then fell. In the other, glucose production fell steadily and in both patients blood lactate concentrations rose. Blood glucose concentrations decreased.Patients with this enzyme deficiency are dependent on the gluconeogenic pathway when fasting and, therefore, ethanol may be potentially hazardous.
Dermatoglyphic study in children with phenylketonuria
Authors: Balci S. , Tanzer F. , Atasu M. , Özalp İ 
Published: June 2005

SummaryDermatoglyphic findings in 19 patients with phenylketonuria (11 male and 8 female), 39 of their relatives (18 female and 21 male) and 500 controls (TRC) were not statistically significant among the three groups studied. There was no definite relationship between the phenylketonuric gene and the dermatoglyphic patterns.The parents of half the phenylketonuria cases are not consanguineous; thus the phenylketonuria gene may be more frequent in Turkey than other European countries.
Incidence and features of galactosaemia in Saudi Arabs
Authors: Moammar H. , Ratard R. , Cheriyan G. , Mathew P. 
Published: June 2005

SummaryOver a 12‐year period (1983 to 1994), 11 cases of classical galactosaemia were identified in the Saudi Aramco Medical Services Organization (SAMSO). This yields an incidence of 12 cases per 100 000 live births in the Eastern Province of Saudi Arabia. A higher proportion of infants presented with infections compared to reports in the literature. Screening for galactosaemia is highly recommended in this high‐risk population.
l‐2‐Hydroxyglutaric aciduria: Neuropathological correlations and first report of severe neurodegenerative disease and neonatal death
Authors: Chen E. , Nyhan W. L. , Jakobs C. , Greco C. M. , Barkovich A. J. , Cox V. A. , Packman S. 
Published: June 2005

Summaryl‐2‐Hydroxyglutaric aciduria is a rare organic aciduria associated with neurological and particularly cerebellar abnormalities. These abnormalities developed in childhood or later in all previously described patients. We report a more severe form ofl‐2‐hydroxyglutaric aciduria in which an infant presented shortly after birth with hypotonia, apnoea, and seizures, leading to death in the perinatal period. Computerized tomography scans of the brain at 1 day and 2 weeks of age showed abnormal low density of the cerebellum. Examination of the brain showed brainstem and cerebellar atrophy with neuronal loss and gliosis in an olivopontocerebellar distribution. The diagnosis ofl‐2‐hydroxyglutaric aciduria should be considered in any non‐dysmorphic newborn with progressive neurological abnormalities and CNS imaging suggesting low density and size of the cerebellum. The diagnostic consideration is based initially on clinical findings. Conventional urine organic acid analysis reveals the presence of 2‐hydroxyglutaric aciduria. Specific diagnosis requires methodologies which distinguish thel‐ from thed‐isomer.
Prenatal and postnatal diagnosis of menkes disease, an inherited disorder of copper metabolism
Authors: Tønnesen T. , Horn N. 
Published: June 2005

Summary105 patients with Menkes disease have been diagnosed from64Cu‐uptake studies in fibroblasts. These results are presented together with chase results following removal of64Cu from the medium for 16 Menkes patients. Second‐trimester prenatal diagnosis has been performed in 80 pregnancies with male karyotype. These64Cu‐uptake results show some overlap between the upper end of the normal range and the lower end of the Menkes range. Results are presented to show that a combination of64Cu‐uptake and chase results offers a better diagnostic potential than64Cu‐uptakeper se. Chorionic villus copper values from 53 first‐trimester prenatal diagnoses are presented. Maternal deciduum from some of these pregnancies contain similar high amounts of copper as found in the chorionic villus samples from affected fetuses.64Cu‐uptake in cultured chorionic villi from affected fetuses and unaffected fetuses is not discriminatory. Chase results seem however to offer a better diagnostic potential.
The inborn errors of peroxisomal β‐oxidation: A review
Authors: Wanders R. J. A. , van Roermund C. W. T. , Schutgens R. B. H. , Barth P. G. , Heymans H. S. A. , van den Bosch H. , Tager J. M. 
Published: June 2005

SummaryIn recent years a growing number of inherited diseases in man have been recognized in which there is an impairment in peroxisomal β‐oxidation. In some diseases this is due to the (virtual) absence of peroxisomes leading to a generalized loss of peroxisomal functions including peroxisomal β‐oxidation. In most inborn errors of peroxisomal β‐oxidation, however, peroxisomes are normally present and the impairment in peroxisomal β‐oxidation is due to the single or multiple loss of peroxisomal β‐oxidation enzyme activities. In all these disorders there is accumulation of very‐long‐chain fatty acids in plasma, which allows biochemical diagnosis of patients affected by an inborn error of peroxisomal β‐oxidation to be done via gas‐chromatographic analysis of plasma very‐long‐chain fatty acids. Subsequent enzymic and immunological investigations are required to identify the precise enzymic defects in these patients. In all inborn errors of peroxisomal β‐oxidation known today there are multiple abnormalities, especially neurological with death usually occurring in the first decade of life. Prenatal diagnosis of these disorders has recently become possible.
A comparison of [9,10‐3H]palmitic and [9,10‐3H]myristic acids for the detection of defects of fatty acid oxidation in intact cultured fibroblasts
Authors: Manning N. J. , Olpin S. E. , Pollitt R. J. , Webley J. 
Published: June 2005

SummaryThe production of tritiated water from [9,10‐3H]myristic acid can be used as a screening assay for the detection of medium‐chain acyl‐CoA dehydrogenase deficiency, multiple acyl‐CoA dehydrogenation defects (glutaric aciduria type 2 and ethylmalonic‐adipic aciduria types), and some types of hydroxydicarboxylic aciduria. Comparison with the release of tritiated water from [9,10‐3H]palmitic acid may give an indication of the chain‐length specificity of the metabolic defect. In a case of ethylmalonic‐adipic aciduria such a prediction has been confirmed by examination of accumulated intermediates in the affected fibroblasts.
Carnitine deficiency with cardiomyopathy presenting as neonatal hydrops: Successful response to carnitine therapy
Authors: Steenhout P. , Elmer C. , Clercx A. , Blum D. , Gnat D. , van Erum S. , Vertongen F. , Vamos E. 
Published: June 2005

SummaryA small‐for‐date infant presented at birth with severe non‐immune hydrops, cardiac failure, metabolic acidosis and hypoglycaemia. Ultrasonography disclosed a cardiomyopathy. Initial therapy consisting of artificial ventilation, inotropes and diuretics resulted in partial disappearance of oedema without significant improvement in cardiac function. Episodes of hypoglycaemia recurred despite continuous glucose influsions.Total serum carnitine from cord blood was 1.65 nmoles/ml and was undetectable on day 20. Oraldl‐carnitine supplements resulted in normoglycaemia, dramatic improvement in cardiac function and restoration of serum carnitine levels to normal values. The infant was thereafter maintained on carnitine therapy. Follow‐up over 1 year showed moderate growth retardation and normal developmental milestones.In order to account for such a severe neonatal presentation of carnitine deficiency, a combination of defective pre‐ and postnatal carnitine supply with an inborn error of carnitine handling is considered. The present case illustrates the need for evaluation of carnitine status in fetuses and neonates presenting with hydrops associated with cardiac failure.
Comparison of patients with complete and partial biotinidase deficiency: Biochemical studies
Authors: Suormala T. M. , Baumgartner E. R. , Wick H. , Scheibenreiter S. , Schweitzer S. 
Published: June 2005

SummarySeventeen partially biotinidase‐deficient patients detected by neonatal screening or family studies were compared with four patients with classical biotinidase deficiency. Using a sensitive HPLC method for biotinidase in plasma (substrate: biocytin) the patients could be divided into two groups: one with residual biotinidase activity, and the second with undetectable biotinidase activity (0‐activity). Biocytin excretion, characteristically elevated in 0‐activity patients, decreased rapidly with increasing residual biotinidase activity and was almost normal when residual activity exceeded 2–3% of mean normal. In one patient with classical disease (0‐activity) biotin deficiency, typical organic aciduria and multiple carboxylase deficiency were found as early as at the second week of life. In contrast, 13 infants with residual activities from 1.2% to 23% had no remarkable clinical or biochemical abnormalities. However, in three 5‐, 14‐ and 15‐year‐old healthy siblings with residual biotinidase activities between 2.3% and 4.2%, biotin deficiency was proven by decreased activities of the mitochondrial carboxylases in lymphocytes (30–57% of mean normal) and, in the older siblings, also by subnormal plasma biotin concentrations. In biotinidase deficiency, biotin depletion presumably occurs earlier in the brain than in other tissues and may thus first affect the central nervous system. For this reason and because of discrete biochemical abnormalities found in a patient with residual biotinidase activity of 8%, we suggest that at least all patients with residual activities below 10% should be treated with biotin.
Type I glycogen storage disease with vasoconstrictive pulmonary hypertension
Authors: Furukawa N. , Kinugasa A. , Inoue F. , Imashuku S. , Takamatsu T. , Sawada T. 
Published: June 2005

SummaryA case of glycogen storage disease (GSD) type I with vasoconstrictive pulmonary hypertension is described.
Identification of new mutations in the ornithine transcarbamylase (OTC) gene in Korean families
Authors: Yoo H.‐W. , Kim G.‐H. , Lee D.‐H. 
Published: June 2005

SummaryOrnithine transcarbamylase (OTC) deficiency, an X‐linked inborn error of the urea cycle, is known to be heterogeneous genetically as well as phenotypically. Molecular defects of Korean patients with OTC deficiency have not been reported. To investigate molecular lesions resulting in OTC deficiency, the OTC genes of unrelated symptomatic or asymptomatic female heterozygotes were amplified exon by exon and analysed by direct sequencing of double‐stranded DNA. Three new mutations, two missense and one nonsense, were detected: (1) a C‐to‐T transition in codon 44 in exon 2 replacing a threonine by an isoleucine (T44I) was found in a late‐onset symptomatic female patient but not in her asymptomatic mother; (2) a C‐to‐T transition in codon 214 creating a newRsaI recognition site in exon 6 and substituting tyrosine for histidine (H214Y) was identified in an asymptomatic female carrier whose son developed acute neonatal onset of OTC deficiency; (3) a C‐to‐T transition in codon 320 (arginine) abolishing aTaqI recognition site and creating a newBClI site in exon 9 with generation of a stop codon (R320X) leading to premature termination in the enzyme. This nonsense mutation was found in a symptomatic female patient and her asymptomatic mother whose son died of OTC deficiency during the neonatal period. In addition, we found a G‐to‐A transition in codon 141 in exon 5 causing substitution of glutamine for arginine (R141Q) in a female obligate heterozygote whose previous three sons succumbed to acute neonatal‐onset OTC deficiency. This missense mutation has been described previously and is known to eliminate aTaqI recognition site in exon 5.
Comparative biochemical studies in fibroblasts from patients with different forms of Leigh syndrome
Authors: Vazquez‐Memije M. E. , Shanske S. , Santorelli F. M. , Kranz‐Eble P. , Davidson E. , De Vivo D. C. , DiMauro S. 
Published: June 2005

SummaryWe have compared respiratory chain enzyme activities, ATP synthesis, and ATP hydrolysis in cultured fibroblast mitochondria from patients with Leigh syndrome (LS) due to: (i) cytochrome oxidase (COX) deficiency (#6); (ii) pyruvate dehydrogenase complex (PDHC) deficiency (#4); and (iii) maternally inherited LS (MILS) with the T8993G mutation in the ATPase 6 gene of mtDNA (#5). Enzyme activities were normal in patients with MILS and variably decreased in those with COX and PDHC deficiency. ATP hydrolysis was normal or mildly decreased in all three groups. In contrast, ATP synthesis was decreased in all patients but more markedly in those with MILS, and especially with pyruvate/malate as substrate. These studies show that impaired ATP production is the common feature of all three forms of LS, but it is both more severe and more specific in MILS, consistent with the genetic defect.
Pyruvate carboxylase defect: Metabolic studies on cultured skin fibroblasts
Authors: Oizumi J. , Ng W. G. , Donnell G. N. 
Published: June 2005

AbstractOxidative studies using a number of radioactive carbon‐labelled substrates on intact cultured skin fibroblasts from a patient with pyruvate carboxylase deficiency revealed dysfunction of the Krebs cycle. The suppression of CO2 production from aspartate but not glutamine strongly suggests that the defective function lies in the aspartate‐malate shuttle. Furthermore, there is an unusual dependence on glutamine for the maintenance of growth of the patient's cells compared to normal cells. Glutamine could not be replaced by aspartate supplementation. A secondary defect resulting in accumulation of lipid material was also demonstrated in this study.It is speculated that the intracellular level of oxaloacetate may also be diminished in the patient's cells. Oxaloacetate is primarily generated by the carboxylation of pyruvate catalysed by pyruvate carboxylase.
Partial deficiency of dihydroxyacetone phosphate acyltransferase activity in both classical and infantile Refsum's diseases
Authors: Van Crugten J. T. , Paton B. , Poulos A. 
Published: June 2005

AbstractWe measured the activity of dihydroxyacetone phosphate acyltransferase (DHAP‐AT) in fibroblasts of controls and patients with classical Refsum's disease (RD), infantile Refsum's disease (IRD) and Zellweger's syndrome (ZS). We confirmed that DHAP‐AT activity is severely reduced in ZS fibroblasts and amniocytes. We also demonstrated a partial deficiency of DHAP‐AT activity in RD and IRD fibroblast cultures. These diseases are probably distinct but related entities in which peroxisomal biogenesis is affected to varying degrees.
Ornithine transcarbamylase deficiency: a case with a truncated enzyme precursor and a case with undetectable mRNA activity
Authors: Kodama H. , Ohtake A. , Mori M. , Okabe I. , Tatibana M. , Kamoshita S. 
Published: June 2005

AbstractThe cell‐free translation of ornithine transcarbamylase (OTC) mRNA from the livers of two heterozygous patients (from different families) with OTC deficiency was performed. The enzyme activities and the immunoreactive proteins in both patients were about 5% of those in controls. Immunoblotting assay of liver extracts from both patients showed decreased amounts of the OTC protein. The mRNA from the liver of patient 1 directed the synthesis of a very small amount of OTC precursor of normal subunit size (40 000 Da), whereas that from patient 2 directed the synthesis of small amounts of two distinctin vitro products; one was 40 000 Da and the other was about 30 000 Da. Thein vitro product of normal precursor synthesized with mRNA from patient 2 was converted to mature‐sized OTC by isolated rat liver mitochondria, whereas the smaller product was degraded during the incubation with the mitochondria. These results indicate that in both patients the translatable level of mRNA for active OTC from liver cells was much lower than that in the controls. The results also suggest that in patient 2, the smaller product presumably derived from an abnormal gene could not be transferred to the mitochondria.
A new patient with hyperornithinaemia, hyperammonaemia and homocitrullinuria treated early with low protein diet
Authors: Gjessing L. R. , Lunde H. A. , Undrum T. , Broch H. , Alme A. , Lie S. O. 
Published: June 2005

AbstractThe characteristic biochemical disturbances of the amino acid and pyrimidine metabolism are described and illustrated by the first case of the HHH syndrome reported in Norway. The disorder was treated with a low protein diet at an early age and the patient developed normally on this diet.
Plasma amino acid values and pancreatic β‐cell function in phenylketonuria
Authors: Antonozzi I. , Carducci C. , Vestri L. , Manzari V. , Dominici R. 
Published: June 2005

AbstractIn 16 phenylketonuric (PKU) patients aged 5–12 years, plasma glucose, immunoreactive insulin (IRI), C‐peptide (CP) and plasma amino acids were measured in basal conditions and under a standard oral glucose tolerance test (OGTT).The β‐cell response to OGTT was higher in PKU patients than in normal subjects as demonstrated by peak levels and areas under the curves of plasma concentrations of IRI and of CP. A significant correlation was observed between plasma phenylalanine values and both IRI and CP ‘output’ in PKU patients. Mean concentrations of branched chain amino acids and tyrosine in plasma decreased significantly during OGTT, while phenylalanine values increased in PKU subjects.
A new family affected by the syndrome of hyperornithinaemia, hyperammonaemia and homocitrullinuria
Authors: Rodes M. , Ribes A. , Pineda M. , Alvarez L. , Fabregas I. , Alvarez E. Fernandez , Coude F. X. , Grimber G. 
Published: June 2005

AbstractWe have reported three cases of hyperornithinaemia associated with hyperammonaemia and homocitrullinuria (HHH). They deal with two brothers and a sister from a family where the parents and four other children are healthy on clinical and biochemical examination. The biochemical findings in our patients indicate the existence of a defect in the transport of ornithine into the mitochondria. Cultured skin fibroblasts from two of these patients incorporated six times less [14C]ornithine into protein as compared to control cells. The most characteristic sign of the clinical picture is the progressive spastic paraparesis found in one of the cases. Ornithine supplementation and restricted protein intake may be useful in the treatment of this syndrome since after three years of treatment the clinical response was favourable and the patients showed no adverse clinical effects.
Molecular genetics of phosphorylase kinase: cDNA cloning, chromosomal mapping and isoform structure
Authors: Kilimann M. W. 
Published: June 2005

SummaryA deficiency in phosphorylase kinase is responsible for several forms of glycogen storage disease which differ in heredity and affected tissues. This is so because phosphorylase kinase consists of four different subunits and has multiple tissue‐specific isoforms. To elucidate the molecular basis of phosphorylase kinase deficiencies, the cDNAs encoding the subunitsα andβ were cloned and sequenced. Each subunit was shown to be encoded by a single gene. Theα subunit gene was mapped to chromosome Xq12–q13 and theβ subunit gene to chromosome 16q12–q13. Isoform cDNAs reveal differential mRNA splicing. Thus, the stage is set for the molecular characterization of the genes and their deficiency mutations.
Disorders of glycoprotein degradation
Authors: Cantz M. , Ulrich‐Bott B. 
Published: June 2005

SummaryThe intracellular degradation of glycoproteins occurs predominantly in the lysosomes through the concerted action of proteases and glycosidases. Genetic defects in any of the enzymes cleaving the oligosaccharide side chains lead to specific diseases because of an excessive lysosomal accumulation of partially degraded material, mostly oligosaccharides.This paper presents an overview of the biochemistry and the clinical spectrum of this group of diseases including sialidosis, galactosialidosis,α‐andβ‐mannosidosis, fucosidosis, aspartylglucosaminuria, andα‐N‐acetylgalactosaminidase deficiency (Schindler disease). In addition, the sialic acid storage disorder (Salla disease) which is caused by a defect in the lysosomal transport of this acidic monosaccharide is included because of functional and clinical correlations.
α‐ andβ‐mannosidoses
Authors: Cooper A. , Hatton C. E. , Thornley M. , Sardharwalla I. B. 
Published: June 2005

SummaryClinical, pathological and biochemical findings in the mannosidoses are described. Family studies showed granulocyte‐rich white cell fractions to be the tissue of choice for carrier detection inβ‐mannosidosis. Metabolic labelling studies using [3H] mannose demonstrated accumulation of Manβ1‐4GlcNAc in cultured skin fibroblasts from a patient with this condition. Alternative methods of egress from lysosomes were suggested for this compound by its secretion into culture medium and apparent reduction of storage with time in cultures.β‐mannosidase deficient goats are not thought to be a true animal model of the human condition, as although they showed a similar enzyme deficiency, the clinical presentation is much more severe and the major storage material (Manβ1‐4GlcNAcβ1‐4GlcNAc) is different.
Clinical application of somatic gene therapy in inborn errors of metabolism
Authors: Ledley F. D. 
Published: June 2005

SummaryRapid advances in recombinant DNA and gene transfer technologies provide the potential for somatic gene therapy of inborn errors of metabolism in which the genetically defective function will be restored by transfer of a normal gene into somatic cells. The therapeutic potential and safety of gene therapy has been explored in cultured cells and experimental animals, but therapeutic clinical trials have not yet been proposed or performed. The technologies which may make somatic gene replacement therapy feasible need to be considered and criticised from a clinical perspective. Clinical trials will be necessary to determine the efficacy of somatic gene therapy and address concerns about safety.