bluuebunny/crossref_metadata_2025_split huggingface dataset:
3‐Hydroxy‐3‐methylglutaryl‐coenzyme A (HMG‐CoA) lyase deficiency in Saudi Arabia
Authors: Ozand P. T. , Al Aqeel A. , Gascon G. , Brismar J. , Thomas E. , Gleispach H. 
Published: June 2005

SummaryDeficiency of 3‐hydroxy‐3‐methylglutaryl‐CoA lyase has been studied in 11 Saudi infants. The diagnosis was established by the measurement of enzyme activity in lymphocytes, in fibroblasts and, in seven patients, by the gas chromatography/mass spectrometer pattern of excreted organic acids in the urine. In seven infants the disease caused a devastating acidotic attack within the first day of life, while in two the crisis occurred by the third day of life. In two infants from one family the disease appeared later in infancy. The clinical presentation of an acidotic attack is lethargy, hyperpnoea, tachypnoea and seizures, either at birth (two infants), following first feeding (in five infants), or following vomiting or refusal of food in later infancy. The acidotic attacks recurred later in life following minor illness or refusal to eat. The acidosis of this enzyme deficiency progresses rapidly, leading to cardiopulmonary arrest and death within hours of onset unless treated promptly. In four surviving infants diagnosed and treated early, development is normal. Magnetic resonance and computerized tomography brain scans in these infants, however, show white matter lesions and mild atrophy.
Phenotypic variability and abnormal type I collagen unstable at body temperature in a family with mild dominant osteogenesis imperfecta
Authors: Tenni R. , Biglino P. , Dyne K. , Rossi A. , Filocamo M. , Pendola F. , Brunelli P. , Buttitta P. , Borrone C. , Cetta G. 
Published: June 2005

SummaryAutosomal dominant inheritance of a mild form of osteogenesis imperfecta (osteogenesis imperfecta type I) with different phenotypic expression was found in a family. Phenotypic expression was different for the affected mother and son, in the presence of the same biochemical results.Dermal fibroblast cultures synthesized normal and mutant type I collagen α chains. Collagen heterotrimers containing abnormal chains were overmodified along the entire triple helical domain and showed an unusually low denaturation temperature, so far found only in lethal cases. The mild phenotype in the family is probably due to the fact that abnormal type I collagen molecules are more likely to be degraded than utilized in the extracellular matrix.
Clinical and biochemical findings in parents of children with vitamin D‐dependent rickets type II
Authors: Yokota I. , Takeda E. , Ito M. , Kobashi H. , Saijo T. , Kuroda Y. 
Published: June 2005

SummaryVitamin D‐dependent rickets type II is a rare disease caused by a disorder of the receptor for 1, 25‐dihydroxyvitamin D (1, 25(OH)2D). Several parameters of this receptor‐effector system were investigated to obtain biochemical information on the presumed heterozygotes of vitamin D‐dependent rickets type II in parents of five patients and in their age‐matched controls. It was found that the serum concentrations of 1,25‐(OH)2D and 24,25‐dihydroxy‐vitamin D (24, 25(OH)2D), and the ratio of 1,25‐(OH)2D/24,25‐(OH)2D differed significantly in the parents from those of the patients and the respective control groups. In the parents' cultured skin fibroblasts, the activity of 25‐hydroxyvitamin D‐24‐hydroxylase induced by 10−8 mol/L 1, 25‐(OH)2D3 ranged from 50 to 82% of that of their controls (versus 1–13% of controls for the patients). The binding capacity of the parents' [3H]1, 25‐(OH)2D3 to the nucleus was 38–54% of that of their control subjects (versus 7–27% of controls for the patients). The parents' values were thus in a range between those of the patients and the control groups. These findings suggest that, in the parents, a partial impairment of the receptor system for 1,25‐(OH)2D led to an imbalance of vitamin D metabolism, thus confirming that vitamin D‐dependent rickets type II is an autosomal recessive inherited disease. Serum concentrations of 1, 25‐(OH)2D and 24,25‐(OH)2D may provide useful parameters for detecting heterozygotes of this disease.
Neutral lipid storage disease with ichthyosis: Serum apolipoprotein levels and cholesterol metabolism in monocyte‐derived macrophages
Authors: Bergman R. , Aviram M. , Bitterman‐Deutsch O. , Oiknine Y. , Shemer A. , Srebnik A. , Brook J. G. , Friedman‐Birnbaum R. 
Published: June 2005

SummaryNeutral lipid storage disease with ichthyosis (NLSDI) is an inherited metabolic disorder characterized by accumulation of neutral lipids, in a wide variety of cells, by a still unknown mechanism. Previous studies have shown normal cholesterol content in NLSDI granulocytes, fibroblasts and skin cells. Monocyte‐derived macrophages possess an additional pathway of cholesterol uptake, which is not shared by these cells and which is not regulated by intracellular cholesterol levels. This pathway is thought to play a rôle in the process of atherosclerosis. Three NLSDI patients were studied. The serum levels of triglycerides, cholesterol, high‐density lipoprotein cholesterol, and apolipoproteins A‐I and B were within normal limits in all three patients. The intracellular levels of free and esterified cholesterol were measured in the monocyte‐derived macrophages of one patient and found to be normal, while the triglyceride concentrations were twice as high as normal. The cholesterol esterification rates, which serve as a sensitive indicator of intracellular changes in cholesteryl ester levels, were normal in the monocyte‐derived macrophages of all three patients. These findings provide further evidence that cholesterol metabolism is not disturbed in NLSDI, and it may be inferred that in this respect these patients are not at increased risk for atherosclerosis.
Fruits and vegetables are a source of galactose: Implications in planning the diets of patients with Galactosaemia
Authors: Gross K. C. , Acosta P. B. 
Published: June 2005

SummaryIt has become apparent that removing dairy products from the diets of patients with galactosaemia does not sufficiently diminish the deleterious signs. We have determined the amount of soluble monomeric galactose in 45 fruits and vegetables using capillary gas chromatography and selective ion monitoring. Galactose contents ranged from less than 0.1 mg per 100 g of tissue in artichoke, mushroom, olive, and peanut to 35.4 mg per 100 g in persimmon. Fruits and vegetables with over 10 mg per 100 g included date, papaya, bell pepper, tomato and watermelon. These results will provide important data for planning the diets of patients with galactosaemia.
Biosynthesis of tetrahydrobiopterin in man
Authors: Curtius H. ‐Ch. , Heintel D. , Ghisla S. , Kuster Th. , Leimbacher W. , Niederwieser A. 
Published: June 2005

AbstractThe biosynthesis of tetrahydrobiopterin (BH4) from dihydroneopterin triphosphate (NH2P3) was studied in human liver extract. The phosphate‐eliminating enzyme (PEE) was purified ~750‐fold. The conversion of NH2P3 to BH4 was catalyzed by this enzyme in the presence of partially purified sepiapterin reductase, Mg2+ and NADPH. The PEE is heat stable when heated at 80°C for 5 min. It has a molecular weight of 63 000 daltons. One possible intermediate 6‐(1′‐hydroxy‐2′‐oxopropyl)5,6,7,8‐tetrahydropterin(2′‐oxo‐tetrahydropterin) was formed upon incubation of BH4 in the presence of sepiapterin reductase and NADP+ at pH 9.0. Reduction of this compound with NaBD4 yielded monodeutero threo and erythro‐BH4, the deuterium was incorporated at the 2′ position. This and the UV spectra were consistent with a 2′‐oxo‐tetrahydropterin structure. Dihydrofolate reductase (DHFR) catalyzed the reduction of BH2 to BH4 and was found to be specific for the pro‐R‐NADPH side. The sepiapterin reductase catalyzed the transfer of the pro‐S hydrogen of NADPH during the reduction of sepiapterin to BH2. In the presence of crude liver extracts the conversion of NH2P3 to BH4 requires NADPH. Two deuterium atoms were incorporated from (4S‐2H)NADHP in the 1′ and 2′ position of the BH4 side chain. Incorporation of one hydrogen from the solvent was found at position C(6). These results are consistent with the occurrence of an intramolecular redox exchange between the pteridine nucleus and the side chain and formation of 6‐pyruvoyl‐5,6,7,8‐tetrahydropterin(tetrahydro‐1′‐2′‐dioxopterin) as intermediate.
Biotinidase deficiency: A novel vitamin recycling defect
Authors: Wolf B. , Grier R. E. , Secor McVoy J. R. , Heard G. S. 
Published: June 2005

AbstractThe recent finding that biotinidase deficiency is the primary biochemical defect in late‐onset multiple carboxylase deficiency has stimulated new interest in the inherited disorders of biotin‐dependent carboxylases. The clinical and biochemical features of biotinidase deficiency are discussed. We also speculate about two exciting areas currently being investigated: the localization of action of biotinidase, and the possible role of the enzyme as a binding or carrier protein for biotin.
Biotinidase deficiency: Factors responsible for the increased biotin requirement
Authors: Baumgartner E. R. , Suormala T. , Wick H. , Bausch J. , Bonjour J. ‐P. 
Published: June 2005

AbstractInability to recycle biotin from endogenous biocytin in congenital biotinidase deficiency is associated with increased requirement of exogenous free biotin. We have observed that severe biotin depletion with clinical and biochemical consequences occurs within 12 days after birth in a newborn patient and within 15–20 days after withdrawal of biotin supplementation in four other patients. Our studies have shown that:

Urinary loss of biotin and biocytin are major causes for this rapid biotin depletion.

Intestinal absorption of biotin seems to be normal at least at the loading dose of 1.5 µg/kg.

At normal or subnormal plasma biotin concentrations biocytin is found in low concentrations (below 1 nmoll−1) in plasma of patients but at much higher concentrations in urine (100–600 nmoll−1).

An oral load of biocytin results in patients in unchanged biotin levels but in a marked rise of biocytin in plasma followed by rapid renal excretion of biocytin whereas in controls biotin levels in plasma increase rapidly and biocytin remains below detection levels.
The role of vitamin E in the treatment of the neurological features of abetalipoproteinaemia and other disorders of fat absorption
Authors: Muller D. P. R. , Lloyd J. K. , Wolff O. H. 
Published: June 2005

AbstractStudies in patients with abetalipoproteinaemia and other chronic and severe fat malabsorptive states, and neuropathological studies in the vitamin E‐deficient human, monkey and rat indicate that vitamin E is important for normal neurological function. Appropriate vitamin E supplementation is, therefore, advisable for all patients with chronic fat malabsorption who have low serum vitamin E concentrations.
Mutation of the 97‐197‐197‐1subunit of the pyruvate dehydrogenase complex, in relation to heterogeneity
Authors: Kitano A. , Endo F. , Matsuda I. , Miyabayashi S. , Dahl H‐H. M. 
Published: June 2005

SummaryPyruvate dehydrogenase complex was studied using bio‐ and immunochemical methods in cultured cells derived from two patients with the severe type and one patient with the mild type of pyruvate dehydrogenase complex deficiency. In patients 1 and 2, enzyme activity was all but undetectable and associated with the absence of E1α subunit of the complex. Patient 3 had a slightly reduced level of enzyme activity, and this was associated with a larger form of E1α subunit. The amount and size of E1α mRNA in the three patients was similar to that of control samples. Thus, the severity of E1α deficiency in these three patients is likely to depend on the type of mutation in the pyruvate dehydrogenase E1α subunit and the synthesis and degradation rate of the subunit.
A therapeutic trial withN‐acetylcysteine in subjects with hereditary glutathione synthetase deficiency (5‐oxoprolinuria)
Authors: Mårtensson J. , Gustafsson J. , Larsson A. 
Published: June 2005

SummaryIn a therapeutic trial, the effect of short‐term low‐dosageN‐acetylcysteine supplementation on glutathione metabolism was investigated in two patients with hereditary glutathione deficiency (5‐oxoprolinuria). Clinical and neurophysiological examinations of the patients indicated progressive neurological damage.The pretreatment concentrations of total and free glutathione in leukocytes were 15–20% of normal, whereas the corresponding γ‐glutamylcysteine levels were increased. In plasma, the glutathione concentrations were similarly decreased, but no γ‐glutamylcysteine was detected. Total glutathione in erythrocytes was markedly decreased. Low urinary excretion of cysteinylglycine, cyst(e)ine, taurine,N‐acetylcysteine, mercaptolactate and mercaptoacetate and reduced leukocyte taurine levels constituted additional evidence of decreased intracellular availability of cysteine, i.e. glutathione.Oral supplementation withN‐acetylcysteine (5 mg/kg × 3/day) had no effect on acid‐base balance, erythrocyte glutathione levels or 5‐oxoproline concentrations in plasma and urine. In leukocytes, the glutathione concentrations were increased by 20–30%, whereas the γ‐glutamylcysteine levels were essentially unaltered. In parallel, the urinary excretion of cysteinylglycine was increased and the leukocyte levels and urinary outputs of sulphur amino acids were restored. No side‐effects of the treatment were noted. The results indicate thatN‐acetylcysteine may be of value in increasing the low intracellular glutathione concentrations and cysteine availability in patients with hereditary glutathione synthetase deficiency.
Prenatal diagnosis of infantile sialic acid storage disease in a twin pregnancy
Authors: Lake B. D. , Young E. P. , Nicolaides K. 
Published: June 2005

SummaryA diagnosis of infantile sialic acid storage disease was made in an infant who died aged 17 months. In the mother's next pregnancy no morphological or biochemical abnormality was found in chorionic villi, amniotic fluid, cultured amniotic fluid cells or fetal blood and a normal boy was born. In the subsequent pregnancy an ultrasound scan revealed a twin pregnancy. Chorionic villus samples were obtained from both twins and microscopic and biochemical analysis indicated one twin to be affected with sialic acid storage disease. Selective fetocide was performed. The unaffected twin proceeded to term.
Homocitrullinuria and homoargininuria in lysinuric protein intolerance
Authors: Kato T. , Sano M. , Mizutani N. 
Published: June 2005

SummaryA 14‐year‐old boy with lysinuric protein intolerance had increased plasma and urinary concentrations of homocitrulline and homoarginine. The accumulation of carbamylphosphate due to depleted supply of ornithine for the urea cycle may be responsible for the enhanced synthesis of homocitrulline and homoarginine. A renal clearance study showed that the tubular transport of homoarginine in the patient was impaired. In lysinuric protein intolerance, membrane transport system for homoarginine may be defective because it is presumed that homoarginine shares a common transport system with the dibasic amino acids.
Cystinuria and its treatment: 25 years experience at St. Bartholomew's hospital
Authors: Stephens A. D. 
Published: June 2005

SummaryCystinuria is an inherited condition affecting the active transport of the diamino acids cystine, ornithine, lysine and arginine across the renal tubule and the small intestine. The only clinical effect is the production of urinary tract stones and if these can be prevented the affected individuals can lead a normal life. In many people cystine stones can be dissolved and new stone formation prevented by a high fluid intake, but if this does not succeed regular treatment with penicillamine will do so. Although many side‐effects have been described with penicillamine treatment it is rare for them to be severe enough to prevent its use in patients with cystinuria. Since the clinical effects of cystinuria can be prevented by either a high fluid intake or by penicillamine it is important to make the diagnosis in affected individuals as soon as possible and cystinuria should therefore be considered in all people (regardless of age) who form urinary stones.
Neonatal pyruvate carboxylase deficiency with renal tubular acidosis and cystinuria
Authors: Oizumi J. , Shaw K. N. F. , Giudici T. A. , Carter M. , Donnell G. N. , Ng W. G. 
Published: June 2005

AbstractThis report concerns a patient with severe congenital lacticacidosis associated with proximal renal tubular acidosis and cystinuria. Enzyme studies with cultured skin fibroblasts obtained from the patient revealed zero pyruvate carboxylase activity, but propionyl‐CoA carboxylase activity was normal. Administration of various vitamins in large amounts did not improve the clinical condition. In contrast, the patient began to thrive when her diet was supplemented with aspartic acid, asparagine, glutamic acid, and glutamine. The particular dietary treatment used and the biochemical findings merit consideration for management of future cases.
Thermal activation of hexosaminidase A in a genetic compound with Tay‐Sachs disease
Authors: Ben‐Yoseph Y. , Baylerian M. S. , Momoi T. , Nadler H. L. 
Published: June 2005

AbstractIncrease in total hexosaminidase activity has been observed during heat treatment of serum and leukocyte specimens from a 1‐year‐old boy with cherry‐red spot and severe and progressive mental and motor deterioration. The activity increased 40% in the first 40–70 min of incubation at 50°C and pH 4.3, but declined thereafter and was only slightly above the initial activity in the final 2–3 h of incubation. Heat treatment of specimens from family members revealed very reduced rates of inactivation of hexosaminidase in the proband's father and some paternal relatives, whereas those of the mother and some maternal relatives were indistinguishable from those of Tay‐Sachs carriers. Mixing experiments with enzyme preparations from the proband, normal controls and patients with Tay‐Sachs disease resulted in additive values and did not support the possibility of inhibitor‐ or activator‐related defect. Fractionation of heat‐treated samples by ion exchange chromatography and electrophoresis, as well as examination of the separated fractions for their thermostability, have shown that hexosaminidase A is the activated component and hexosaminidases B, I1 and I2 are not affected. These findings suggest that the patient is a genetic compound and the apparent thermal activation is probably due to formation of hexosaminidase A from altered α‐subunits produced by the paternal mutant α‐allele and β‐subunits produced by the normal β‐alleles.
Physical and kinetic properties of β‐glucosidase in Gaucher disease
Authors: Karazeh A. , Carroll M. 
Published: June 2005

AbstractMembrane‐bound ‘acid’ β‐glucosidase of human spleen was solubilized with either sodium cholate or ‘Cutscum’. The solubilized enzyme in type 1 (adult) Gaucher disease was less heat‐stable than the normal enzyme, and when precipitated by ammonium sulphate it had a higher apparent molecular weight than the corresponding normal enzyme. The normal β‐glucosidase was activated by taurocholate, whereas the Gaucher enzyme was inhibited. The decrease in ‘acid’ β‐glucosidase activity in Gaucher disease was associated with a profound deficiency of that form of the enzyme which bound to Concanavalin A. The results are consistent with faulty processing of newly synthesized ‘acid’ β‐glucosidase in type 1 Gaucher disease.
Problems of prenatal diagnosis of non‐ketotic hyperglycinaemia
Authors: Wendt L. V. , Similä S. , Ruokonen A. , Hartikainen‐Sorri A. ‐L. 
Published: June 2005

AbstractNon‐ketotic hyperglycinaemia (NKH) is a rare disorder of amino acid metabolism, causing severe, frequently lethal neurological symptoms in the neonatal period. There is no curative therapy, and attempts at prenatal diagnosis have been unsuccessful.In the present study the usefulness of the determination of the glycine/serine ratio in the prenatal diagnosis of NKH was studied. The glycine/serine ratio of the amniotic fluid of the last trimester of pregnancies with a fetus affected with NKH was higher (8.5 ± 3.3; mean ± SD) than in pregnancies of NKH‐heterozygote mothers with a healthy fetus (4.1 ± 1.7) or than in pregnancies of healthy mothers (4.3 ± 1.5). There is, however, overlapping of individual values, which limits the usefulness of this test for prenatal diagnosis of NKH.
Xanthine oxidase deficiency and ‘Dalmatian’ hypouricaemia: Incidence and effect of exercise
Authors: Harkness R. A. , Coade S. B. , Walton K. R. , Wright D. 
Published: June 2005

AbstractIn order to study the effects of raising the hypoxanthine concentration in plasma on its metabolism and renal handling, the effects of intense exercise have been investigated in a patient with xanthine oxidase deficiency. Despite the 90‐fold increased concentration of hypoxanthine in plasma above resting levels in normal individuals, the intracellular concentration of the initial product of hypoxanthine in cells, IMP, was unaffected. Evolution may have stabilized intracellular nucleotide concentrations against the large fluctuations in plasma hypoxanthine which occur during exercise. The renal handling of hypoxanthine is consistent with ‘filtration’. In contrast, xanthine clearances may exceed those for creatinine and urinary concentrations do not correlate with those for creatinine; ‘secretion’ may be involved. Xanthine excretion may reflect guanine breakdown. A retrospective survey of urate concentrations in blood from 47 420 patients followed by further selected investigations detected 2 women with persistent marked hypouricaemia and high urinary urate clearances, ‘Dalmatian’ hypouricaemia. High pressure liquid chromatographic analysis of plasma extracts can distinguish xanthine oxidase deficiency from other causes of hypouricaemia.