bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of steroid metabolic profiling as an aid in the diagnosis of familial precocious puberty, a subgroup of true precocious puberty
Authors: Pike A. W. , Klein J. L. , Gotlin R. W. , Fennessey P. V. 
Published: June 2005

AbstractWe report the results of a study of a rare form of true precocious puberty in a family with a history of the condition. Only the male members manifest the trait, whereas it appears to be carried by both males and females. Routine urinary steroid analysis rapidly eliminated most of the classical enzyme defects associated with premature sexual maturation. Further investigation of urinary steroid extracts using gas chromatography and gas chromatography‐mass spectrometry revealed essentially normal prepubertal androgen values for the proband A at 4 years of age, and for his affected and carrier relatives when compared with healthy age‐matched individuals. While his plasma gonadotropin levels were in the prepubertal range, his plasma testosterone value was significantly elevated with values just below the normal range for an adult male.This is the fourteenth reported family with a vertical pattern of familial sexual precocity, but the first to have a steroid profile. Analysis suggests sex‐limited autosomal dominance with a greater than 90% penetrance. The elevated plasma testosterone concentration, prepubertal plasma gonadotropin concentration, minimal histopathologic evidence of gametogenesis and only moderate increase in testicular volume over the five‐year course of follow‐up support a diagnosis of the recently described condition of familial gonadotropin independent sexual precocity. The gas chromatography‐mass spectrometry urinary profiling shows elevated cortisol output but otherwise normal adrenal function.
Infantile Refsum's disease: Biochemical findings suggesting multiple peroxisomal dysfunction
Authors: Poll‐The B. T. , Saudubray J. M. , Ogier H. , Schutgens R. B. H. , Wanders R. J. A. , Schrakamp G. , van den Bosch H. , Trijbels J. M. F. , Poulos A. , Moser H. W. , van Eldere J. , Eyssen H. J. 
Published: June 2005

AbstractInfantile Refsum's disease was diagnosed in three male patients, presenting with facial dysmorphia, retinitis pigmentosa, neurosensory hearing loss, hepatomegaly, osteopenia and delayed growth and psychomotor development.An elevated plasma phytanic acid concentration and a deficient phytanic acid oxidase activity in fibroblasts were found with an accumulation of very long chain fatty acids in plasma and fibroblasts. There were elevated pipecolic acid levels in plasma, urine and CSF, and abnormal bile acid metabolites in plasma.Deficient activity of acylCoA: dihydroxyacetone phosphate acyl transferase was found in thrombocytes and fibroblasts of these patients as well as an impairedde novo plasmalogen biosynthesis in fibroblasts. These biochemical abnormalities, previously described in the Zellweger syndrome, suggest multiple peroxisomal dysfunction in our patients.
Lymphoid cell lines as a model system for the study of Wolman's disease: Enzymatic, metabolic and ultrastructural investigations
Authors: Nègre A. , Salvayre R. , Maret A. , Vieu C. , Bes J. C. , Borrone C. , Durand P. , Douste‐Blazy L. 
Published: June 2005

AbstractEpstein‐Barr virus (EBV) transformed lymphoid cell lines (LCL) were established from blood lymphocytes of a patient affected with Wolman's disease (WD) and from her parents. These LCL showed a severe deficiency in acid lipase activity using every substrate in comparison to LCL from normal subjects, in which acid lipase activity was similar to that in blood lymphocytes. In the LCL from Wolman's disease a major accumulation of neutral lipids was observed, mainly cholesteryl esters, CE (amount around 7 times higher than in normal cells and ratio of esterified/free cholesterol increased by 10 times) and to a lesser extent triglycerides, TG (amount increased by 1.5 times). Electron microscopy showed the storage vacuoles of neutral lipids quite characteristic of this lysosomal disease. The reported data demonstrated the validity of transformed LCL as a cellular model system in culture for experimental studies of Wolman's disease and for investigating the lysosomal metabolism of neutral lipids.
Direct identification of propionylcarnitine in propionic acidaemia: Biochemical and clinical results of oral carnitine supplementation
Authors: Duran M. , Ketting D. , Beckeringh T. E. , Leupold D. , Wadman S. K. 
Published: June 2005

AbstractUrinary short‐chain acylcarnitine in a patient with propionic acidaemia and low levels of free carnitine was found to consist mainly of propionylcarnitine. The compound was isolated by sequential paper and thin layer chromatography and identified by ammonia desorption chemical ionization mass spectrometry. Treatment of the patient with oral carnitine supplements led to a near‐normalization of the plasma free carnitine concentrations and an increase in his muscle tone. The propionylcarnitine excretion rose and there was a simultaneous decrease in the methylcitrate output. Carnitine treatment did not prevent the occurrence of an episode of metabolic decompensation.
Liver transplantation in a 23‐year‐old tyrosinaemia patient: Effects on the renal tubular dysfunction
Authors: Kvittingen E. A. , Jellum E. , Stokke O. , Flatmark A. , Bergan A. , Sødal G. , Halvorsen S. , Schrumpf E. , Gjone E. 
Published: June 2005

AbstractOrthotopic liver transplantation was performed on a 23‐year‐old female with hereditary tyrosinaemia. The disorder was diagnosed at 7 years of age due to severe rickets, and the patient was treated with a diet restricted in phenylalanine and tyrosine. Nineteen months before the transplantation she had an acute episode of diffuse gastrointestinal bleeding due to portal hypertension. Three subsequent bleeding episodes with accompanying ascites and signs of encephalopathy were considered life‐threatening.Nine months after the liver transplantation the patient is well, but serum transaminases are slightly elevated. Without dietary restrictions serum tyrosine and inorganic phosphate are normalized, no succinylacetone can be detected in serum, and urinary excretion ofp‐hydroxyphenyllactate andp‐hydroxyphenylpyruvate is normal.Excretion of amino acids, glucose andβ2‐microglobulin decreased significantly after the transplantation but is still elevated. The succinylacetone concentration in urine is about 20% of the preoperative level. After an oral tyrosine load, succinylacetone excretion increased sevenfold but no deterioration of the renal tubular function was observed and no tyrosine metabolites were detectable in serum. The findings indicate that the defective tyrosine metabolism occurs in the kidneys, but does not produce tubular dysfunction. The residual tubular dysfunction of the patient is probably due to irreversible damage of the tubular epithelium.
Multiple implantation of normal amnion into cattle with generalized glycogenosis type II
Authors: McC. Howell J. , Dorling P. R. , Dimarco P. N. , Taylor E. G. 
Published: June 2005

AbstractOne normal and two carrier calves, and two calves affected by generalized glycogenosis type II were given multiple transplants of normal bovine amnion inserted below the external oblique abdominal muscle in the flank. The interval between transplants was approximately 5 months. The amniotic tissue was not acutely rejected but a host versus graft reaction did occur. The level of acid α‐glucosidase activity in the amniotic tissue fell rapidly but was still present 2 months after transplantation. Enzyme levels in blood or other tissues did not rise. Excess glycogen deposition and muscle damage occurred in the affected calves and appeared to progress at a rate similar to that in untreated affected animals. One of the affected animals died aged 16 months, which was the same age as the longest surviving non‐treated animal in our herd. The other treated animal died aged 24 months.
Pompe's disease in Chinese and prenatal diagnosis by determination of α‐glucosidase activity
Authors: Lin C. ‐Y. , Hwang B. , Hsiao K. ‐J. , Jin Y. ‐R. 
Published: June 2005

AbstractWe measured the activities of two major forms of α‐glucosidase in lymphocytes and cultured fibroblasts from normal healthy controls and patients with Pompe's disease by using 4‐methylumbelliferyl‐α‐d‐glucoside as substrate. We found (1) enzyme activity of the pH4 and pH6 forms varied with age, and (2) patients with Pompe's disease showed very low activity of the pH4 form and a low ratio of pH4 to pH6 forms. We established a reference range and were also able to diagnose prenatally the homozygote and heterozygote forms of Pompe's disease which occurred in families of southern Chinese and aborigines in Taiwan. This enzyme biochemical study may be useful in anthropology.
Biochemical study of sialidosis type I in a Russian family
Authors: Tsvetkova I. V. , Petushkova N. A. , Zolotuchina T. V. , Kucharenko V. I. , Rosenfeld E. L. 
Published: June 2005

AbstractA 7‐year‐old boy from a Russian family with decreased vision and a cherry‐red spot but without any somatic and mental abnormalities is described in this paper. The decreased neuraminidase activity in the child's leukocytes and cultured skin fibroblasts and his 10‐fold increase in urinary sialyloligosaccharides allowed us to conclude that he was affected by type I sialidosis. Some other results of the biochemical study of this child and his parents are presented. It is the first case of sialidosis in the Russian population.
Normal dolichol concentration in urine sediments from four patients with neuronal ceroid lipofuscinosis (Batten's disease)
Authors: Paton B. C. , Poulos A. 
Published: June 2005

AbstractThe dolichol contents of urine sediments from a patient with infantile (Santavuori), a patient with late infantile (Jansky‐Bielschowsky) and two patients with juvenile (Spielmeyer‐Vogt) neuronal ceroid lipofuscinosis (Batten's disease) were not elevated when compared to those from healthy controls.
Purification and characterization of sialic acid containing materials accumulated in cultured skin fibroblasts from a patient with type II sialidosis
Authors: Scocca J. R. , Thomas G. H. , Miller C. , Reynolds L. 
Published: June 2005

AbstractSialyl conjugates which accumulate in sialidase deficient fibroblasts were made radioactive in the sialic acid moiety by culturing the cells in the presence of [3H]N‐acetylmannosamine. The accumulated radioactive compounds were fractionated by anion exchange chromatography and gel filtration. At least nine chromatographically distinct sialyl conjugates were obtained. Neutral and amino sugar analysis of these compounds indicated that all were sialyloligosaccharides of the type which could be derived from glycoproteins containing complex,N‐asparagine‐linked carbohydrate groups.
Arylsulphatase C activity in leukocytes of patients and carriers of X‐linked ichthyosis
Authors: Herrmann F. H. , Grimm U. , Hadlich J. 
Published: June 2005

AbstractIn Triton X‐100 solubilized leukocytes of 17 patients and 8 obligate carriers of X‐linked recessive ichthyosis (XLI) the activity of arylsulphatase C (ASC) was determined and expressed as the ratio to β‐galactosidase activity. The ASC/β‐gal ratio of XLI patients is markedly decreased (range 0.07–0.48) in comparison to the corresponding control group of males (range 1.3–2.7). The enzyme ratios of 8 obligate carriers of XLI are decreased (range 0.90–1.9) in comparison to the normal females (2.13–5.52). These results indicate that the determination of the enzyme ratio of ASC/β‐gal in Triton X‐100 solubilized leukocytes is a sensitive test for biochemical identification of patients and probably of carriers of XLI.
Mechanisms of blood glucose homeostasis
Authors: Hers H. ‐G. 
Published: June 2005

SummaryThe mechanisms by which glycogen metabolism, glycolysis and gluconeogenesis are controlled in the liver both by hormones and by the concentration of glucose are reviewed. The control of glycogen metabolism occurs by phosphorylation and dephosphorylation of both glycogen phosphorylase and glycogen synthase catalysed by various protein kinases and protein phosphatases. The hormonal effect is to stimulate glycogenolysis by the intermediary of cyclic AMP, which activates directly or indirectly the protein kinases. The glucose effect is to activate the protein phosphatase system; this occurs by the direct binding of glucose to glycogen phosphorylase which is then a better substrate for phosphorylase phosphatase and is inactivated. Since phosphorylasea is a strong inhibitor of synthase phosphatase, its disappearance allows the activation of glycogen synthase and the initiation of glycogen synthesis. When glycogen synthesis is intense, the concentrations of UDPG and of glucose 6‐phosphate in the liver decrease, allowing a net glucose uptake by the liver. Glucose uptake is indeed the difference between the activities of glucokinase and glucose 6‐phosphatase. Since the Km of the latter enzyme is far above the physiological concentration of its substrate, the decrease in glucose 6‐phosphate concentration proportionally reduces its activity.The control of glycolysis and of gluconeogenesis occurs mostly at the level of the interconversion of fructose 6‐phosphate and fructose 1,6‐bisphosphate under the action of phosphofructokinase 1 and fructose 1,6‐bisphosphatase. Fructose 2,6‐bisphosphate is a potent stimulator of the first of these two enzymes and an inhibitor of the second. It is formed from fructose 6‐phosphate and ATP by phosphofructokinase 2 and hydrolysed by a fructose 2,6‐bisphosphatase. These two enzymes are part of a single bifunctional protein which is a substrate for cyclic AMP‐dependent protein kinase. Its phosphorylation causes the inactivation of phosphofructokinase 2 and the activation of fructose 2,6‐bisphosphatase, resulting in the disappearance of fructose 2,6‐bisphosphate. The other major effector of these two enzymes is fructose 6‐phosphate, which is the substrate of phosphofructokinase 2 and a potent inhibitor of fructose 2,6‐bisphosphatase; these properties allow the formation of fructose 2,6‐bisphosphate when the level of glycaemia and secondarily that of fructose 6‐phosphate is high.
Diagnosis of glycogen storage disease
Authors: Shin Y. S. 
Published: June 2005

SummaryGlycogen storage diseases are associated with more than 15 different enzyme deficiencies and can be clinically divided mainly into two groups, those that affect primarily the liver and those that affect principally the muscle. In this report each glycogenosis has been clinically and biochemically documented and possibilities for an accurate and prompt diagnosis of the various types have been summarized. Most of the patients suffering from type II, type III, type IV and type VIa can easily be diagnosed by analysis of peripheral blood cells without the need for tissue biopsies. First trimester diagnosis using chorionic villi is feasible for severe forms of the glycogenoses, type IIa, type IIIa and type IV.
Galactose disorders: An overview
Authors: Holton J. B. 
Published: June 2005

SummaryThere are three separate disorders of galactose metabolism of clinical importance. Galactokinase deficiency mainly causes cataracts which regress without complications providing a galactose‐free diet is started early enough. UDPgalactose‐4‐epimerase deficiency seems extremely rare. A common feature of the two reported cases is nerve deafness. Galactose‐1‐phosphate uridyl transferase deficiency poses the greatest problems because of the poor long‐term outcome in spite of a galactose‐restricted diet, and with no clear indications of how and when the underlying damage occurs. Recent evidence of low erythrocyte and tissue UDPgal levels, associated with ovarian dysfunction, may indicate impaired galactoside synthesis. Administration of uridine corrects the UDPgal depletion and trials in which it is added to the galactose‐restricted diet have begun.
Regulation of galactose metabolism: Implications for therapy
Authors: Segal S. , Rogers S. 
Published: June 2005

SummaryIn view of evidence that dietary therapy of galactose‐1‐phosphate uridyltransferase deficiency has failed to prevent complications of the disorder, there is a need for new strategies in treatment. The enhancement of residual enzyme activity in tissues of galactosaemic patients should provide such an approach. This possibility is derived from knowledge of the regulation of transferase activity in normal animal tissues. The pertinent observations summarized herein are: (1) that hepatic transferase activity is modulated by various cellular metabolites, uridine nucleotides being of particular significance; (2) that transferase activity in the young rat liver is subject to developmental programming with a several‐fold increase after birth; (3) that transferase activity in pregnant rat liver is significantly increased which may be related to hormonal effects of progesterone; and (4) that pharmacological doses of folic acid may increase transferase activity. The basis of such regulation can give insight into sufficient augmentation of the residual activity to increase galactose utilization and thereby better the long‐term outcome.
The mechanisms of cataract formation
Authors: Schmitt C. , Hockwin O. 
Published: June 2005

SummaryThis review summarizes current knowledge concerning cataract formation. Metabolically induced forms of cataract are discussed, but mainly aspects of cataract formation in older patients are described, especially with respect to lens protein modifications and epidemiological results. In most cases, cataract in older people is a multifactorial process and therefore cataracts appear in a multitude of different morphological types. Only accurate documentation of lens disturbances and the use of reproducible methods can provide more detailed information about the complexity of the disease cataract.
Cataract and metabolic disease
Authors: Endres W. , Shin Y. S. 
Published: June 2005

SummaryIn addition to the already recognized metabolic diseases which have been associated with cataract formation, e.g. galactosaemia, galactokinase deficiency, Lowe's syndrome and diabetes, several other disorders can also lead to the development of cataracts. They are sorbitol dehydrogenase deficiency, uridine diphosphate galactose‐4‐epimerase deficiency, marginal maternal transferase and galactokinase deficiency, galactitol and sorbitol accumulation of unknown origin, heterozygosity for galactosaemia and galactokinase deficiency as well as the carrier state for Lowe's syndrome. In this review these metabolic disorders have been divided into five groups according to the age at the first appearance of lens clouding and the possible means of treatment have been discussed.
Plasma polyol levels in patients with cataract
Authors: Jakobs C. , Douwes A. C. , Brockstedt M. , Stellaard F. , Endres W. , Shin Y. S. 
Published: June 2005

SummaryGalactitol and sorbitol concentrations in plasma were determined in patients (with or without cataract) in whom homo‐ or heterozygosity for galactokinase, galactose‐1‐phosphate uridyltransferase, systemic or peripheral UDP‐galactose epimerase and sorbitol dehydrogenase deficiency was confirmed. For the above disorders it can be concluded that elevation of plasma polyols is not always related to the presence or absence of cataract. In all cases with cataract, however, the plasma galactitol or sorbitol levels were elevated. In another group of patients with unexplained congenital or infantile cataracts, but without apparent enzyme defects, mild to moderately elevated concentrations of plasma galactitol or sorbitol were found in about 45%. In 8% of this group the cataract and the elevated plasma galactitol concentration could possibly have been related to partial maternal enzyme deficiency. In all the other cases the elevated plasma polyol concentration remains unexplained but could indicate a further cause of cataract formation due to a hitherto unknown galactose or glucose metabolic aberration.
Schindler disease: An inherited neuroaxonal dystrophy due to α‐N‐acetylgalactosaminidase deficiency
Authors: Desnick R. J. , Wang A. M. 
Published: June 2005

SummaryThe clinical, pathological and biochemical features of a neuroaxonal dystrophy resulting from the deficient activity of lysosomal α‐N‐acetylgalactosaminidase are described. This neurodegenerative disorder was recognized in two brothers who had the typical clinical manifestations and neuropathological lesions observed in patients with Seitelberger disease, the infantile form of neuroaxonal dystrophy. Axonal ‘spheroids’ were observed histologically in the grey matter, and ultrastructural examination revealed the characteristic formations in dystrophic axons in the myenteric plexus and neocortex. Using a newly synthesized fluorogenic substrate, 4‐methylumbelliferyl‐α‐N‐acetylgalactosaminide, the markedly deficient activity ofα‐N‐acetylgalactosaminidase was demonstrated in the affected brothers while their consanguineous parents had intermediate activities, consistent with the autosomal recessive transmission of this disease. No detectableα‐N‐acetylgalactosaminidase was seen in immunoblots using monospecific rabbit antihumanα‐N‐acetylgalactosaminidase antibodies. Abnormally increased amounts of urinary glycopeptides were observed by high resolution thin layer chromatography. Analytical studies identified four of the accumulating urinary compounds, the blood group A trisaccharide GalNAcα1 → 3(Fucα1 → 2)Gal and threeO‐linked glycopeptides, GalNAcα1 →O‐serine and ‐threonine, NeuNAcα2 → 3Galβ1 → 3(NeuNAcα2 → 6)GalNAcα1 →O‐serine and ‐threonine, and NeuNAcα2 → 3Galβ1 → 4GlcNAcβ1 → 6(NeuNAcα2 → 3Galβ1 → 3)GalNAcα1 →O‐serine and ‐threonine. Of eight unrelated patients diagnosed as having infantile neuraxonal dystrophy by pathological studies, none had deficientα‐N‐acetylgalactosaminidase activity, emphasizing the biochemical heterogeneity underlying this diagnostic entity. These findings document the first delineation of a metabolic defect in an inherited neuroaxonal dystrophy and suggest that the axonal pathology in this disorder, and perhaps in the other neuroaxonal dystrophies, results from abnormal glycoprotein metabolism involvingO‐linked glycopeptides.
Advances in the molecular genetics of metachromatic leukodystrophy
Authors: Gieselmann V. , von Figura K. 
Published: June 2005

SummaryMetachromatic leukodystrophy is a lysosomal storage disorder caused by the deficiency of arylsulphatase A (EC 3.1.6.1). This results in the intralysosomal storage of cerebroside sulphate, which leads to a progressive demyelination of the nervous system. The patients usually die within a few years from the onset of symptoms. Clinically, there are different forms of the disease and the molecular basis for this heterogeneity is unknown. The gene for arylsulphatase A has recently been cloned and provides a necessary tool for the exact description of the molecular defects occurring in the different forms of metachromatic leukodystrophy. Metachromatic leukodystrophy can also be caused by the deficiency of an arylsulphatase A activator protein (sphingolipid activator protein B). The cDNA for the precursor of this protein has been isolated and a mutant cDNA of one patient has been analysed. A substantial arylsulphatase A deficiency can also occur in healthy individuals, a phenotype termed pseudodeficiency. Two concurrent mutations have been identified in this low arylsulphatase A activity allele. This permitted the development of a rapid assay which allows the detection of the pseudodeficiency allele. Bone marrow transplantation has been tried in several metachromatic leukodystrophy patients and there is evidence that this treatment might slow or even halt the progression of the disease. A final conclusion as to whether bone marrow transplantation is a suitable therapy for metachromatic leukodystrophy cannot be drawn yet.