Abstract：
:The liver plays an important rôle in protecting the organism from potentially toxic chemical insults through its capacity to convert lipophiles into more water-soluble metabolites which can be efficiently eliminated from the body via the urine. This protective ability of the liver stems from the expression of a wide variety of xenobiotic biotransforming enzymes whose common underlying feature is their ability to catalyse the oxidation, reduction and hydrolysis (Phase I) and/or conjugation (Phase II) of functional groups on drug and chemical molecules. The broad substrate specificity, isoenzyme multiplicity and inducibility of many of these enzyme systems make them particularly well adapted to handling the vast array of different chemical structures in the environment to which we are exposed daily. However, some chemicals may also be converted to more toxic metabolites by certain of these enzymes, implying that variations in the latter may be important predisposing factors for toxicity. Pharmacogenetic defects of xenobiotic biotransformation enzymes, a subclass of inborn errors of metabolism which are manifested only upon drug challenge, introduce marked variation into human populations for the pharmacokinetics and pharmacodynamics of therapeutic and toxic agents, and thus may have important clinical consequences for drug efficacy and toxicity.
journal_name
J Inherit Metab Disjournal_title
Journal of inherited metabolic diseaseauthors
Grant DMdoi
10.1007/BF01797915subject
Has Abstractpub_date
1991-01-01 00:00:00pages
421-30issue
4eissn
0141-8955issn
1573-2665journal_volume
14pub_type
杂志文章,评审abstract：:Neurological manifestations in Lesch-Nyhan disease (LND) are attributed to the effect of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency on the nervous system development. HPRT deficiency causes the excretion of increased amounts of hypoxanthine into the extracellular medium and we hypothesized that H...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-015-9854-4
更新日期：2015-11-01 00:00:00
abstract：:Glutaric aciduria type I is an inborn error of organic acid metabolism that demonstrates a particular temporal vulnerability (acute encephalopathic episodes in infancy) and a spatial vulnerability (acute striatal necrosis, focused on the putamen). Excitotoxic mechanisms involving 3-hydroxyglutaric acid as the major ne...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1023/B:BOLI.0000045767.42193.97
更新日期：2004-01-01 00:00:00
abstract：:The CLN3 gene is involved in juvenile neuronal ceroid lipofuscinosis (JNCL), or Batten-Spielmeyer-Vogt disease, a severe hereditary neurodegenerative lysosomal storage disorder characterized by progressive disease pathology, with loss of vision as the first symptom. Another characteristic of JNCL is the lysosomal accu...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-005-0125-7
更新日期：2005-01-01 00:00:00
abstract：:Thirty patients with early and continuously treated phenylketonuria (PKU) between 8 and 20 years of age were compared with 30 controls, matched individually for age, sex, and educational level of both parents, on behaviour rating scales for parents and teachers as well as a school achievement scale. PKU patients, as a...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/a:1005669610722
更新日期：2000-09-01 00:00:00
abstract：:The mutation N370S accounts for 63% of the mutated glucocerebrosidase alleles of Portuguese type 1 Gaucher patients. It has been shown previously that this mutation is linked to the Pv1.1- form of the PvuII polymorphism and suggested that the N370S mutation in glucocerebrosidase alleles has an Ashkenazi Jewish origin....
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF00735401
更新日期：1994-01-01 00:00:00
abstract：:S-Adenosylhomocysteine (S-AdoHcy) hydrolase activity in a lymphoblastoid cell line from a patient with adenosine deaminase deficiency disease (ADA(-)LCL) was found to be approximately 60% of that in ADA (+)lymphoblastoid cell lines. S-AdoHcy hydrolase of ADA(-)LCL was more sensitive to inhibition by 2'-deoxyadenosine ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF02263651
更新日期：1981-01-01 00:00:00
abstract：:It has been suggested that the very low incidence of atherosclerosis in glycogen storage disease type Ia (GSD Ia) subjects might be attributed to elevated levels of uric acid, one of the potent low molecular- weight antioxidants found in plasma. The present communication describes a use of two analytical methods-cycli...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-009-1242-5
更新日期：2009-10-01 00:00:00
abstract：:Large neutral amino acids (LNAAs) have been used on a limited number of patients with phenylketonuria (PKU) with the purpose of decreasing the influx of phenylalanine (Phe) to the brain. In earlier studies on mice with PKU (ENU(2)/ENU(2)), LNAAs were given and a surprising decline in blood Phe concentrations was obser...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,多中心研究
doi：10.1007/s10545-006-0395-8
更新日期：2006-12-01 00:00:00
abstract：:Direct alteration of a gene in the human genome requires an understanding of the role of the gene in metabolism. A gene may need to be introduced into a specific tissue or alternatively it may be possible to use accessible tissue such as bone marrow. The level of gene expression required also needs to be known as does...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01800862
更新日期：1986-01-01 00:00:00
abstract：:We have assessed very low-density lipoprotein apolipoprotein B production, using [15N]glycine as an endogenous marker in a 9-hour primed constant infusion protocol, in four adult male subjects with familial combined hyperlipidaemia and in four normolipidaemic adult male controls. The mean very low-density lipoprotein ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01800473
更新日期：1991-01-01 00:00:00
abstract：:A new acylcarnitine was observed in the plasma and urine of a patient with isolated 3-methylcrotonyl-CoA carboxylase deficiency. Analysis by tandem mass spectrometry of the methyl ester and butyl ester and their fragment ion spectra identified it as a 3-hydroxy-C5-acylcarnitine. Fibroblasts from a second patient were ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF02436004
更新日期：1995-01-01 00:00:00
abstract：:In this review, we describe transcranial electrical stimulation (tES) techniques currently being used in neuroscientific research, including transcranial direct current (tDCS), alternating current (tACS) and random noise (tRNS) stimulation techniques. We explain how these techniques are used and summarise the proposed...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/s10545-018-0181-4
更新日期：2018-07-13 00:00:00
abstract：:Important therapeutic principles were established in developing effective enzyme replacement therapy for patients with Gaucher disease. The background and sequence of the investigations that led to effective delivery of exogenous glucocerebrosidase to the lipid-storing macrophages in patients with Gaucher disease are ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/BF00711365
更新日期：1994-01-01 00:00:00
abstract：:The clinical problems, dietary management and biochemical monitoring over a 40-year period of the longest-surviving patient with maple syrup urine disease are described. Her case illustrates that a good outcome can be obtained with early diagnosis and institution of a diet restricted in branched-chain amino acids. Cha...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-006-0204-4
更新日期：2006-02-01 00:00:00
abstract：:A 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 kinas...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/BF01799500
更新日期：1990-01-01 00:00:00
abstract：:The human genome contains about 3 x 10(9) base pairs which, based on average estimates for the size of coding regions, might suggest an upper limit of about 3 million genes. Evidence from a variety of approaches indicates a much lower figure--in the range 40,000-100,000 genes. Renaturation kinetic analysis reveals the...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/BF00711355
更新日期：1994-01-01 00:00:00
abstract：:Congenital disorders of glycosylation (CDG) are a rapidly growing family comprising >100 genetic diseases. Some 25 CDG are pure O-glycosylation defects. Even among this CDG subgroup, phenotypic diversity is broad, ranging from mild to severe poly-organ/system dysfunction. Ophthalmic manifestations are present in 60% o...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1002/jimd.12025
更新日期：2019-01-01 00:00:00
abstract：:As more states adopt expanded newborn screening for metabolic disorders, the overall number of false positives increases. False-positive screening results have been associated with increased anxiety and stress in parents of infants who require follow-up testing, even after the infant's good health is confirmed. This a...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/s10545-006-0381-1
更新日期：2006-10-01 00:00:00
abstract：:The very long chain fatty acids in cultured fibroblasts from six patients with the cerebro-hepato-renal syndrome of Zellweger, from six of their parents, from three controls, and also in three amniotic fluid control cell lines were analysed by gas chromatography. Increased concentrations of hexacosanoic acid (C26:O) w...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01805473
更新日期：1985-01-01 00:00:00
abstract：:The lipid composition or the liver, spleen, brain, cerebellum and cerebrospinal fluid of a Gaucher disease type II patient who died at the age of 5 months was examined. The glycolipid analysis demonstrated a marked increase of total amounts not only in the peripheral tissues but also in the brain cerebellum and cerebr...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/a:1015137917508
更新日期：2002-02-01 00:00:00
abstract：:Brown-Vialetto-Van Laere syndrome (BVVLS [MIM 211530]) is a rare neurological disorder characterized by infancy onset sensorineural deafness and ponto-bulbar palsy. Mutations in SLC52A3 (formerly C20orf54), coding for riboflavin transporter 2 (hRFT2), have been identified as the molecular genetic correlate in several ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-012-9513-y
更新日期：2012-11-01 00:00:00
abstract：:Maple syrup urine disease (MSUD), an inborn error of amino acids catabolism is characterized by accumulation of branched chain amino acids (BCAAs) leucine, isoleucine, valine and their corresponding alpha-ketoacids. Impact on the cognitive development has been reported historically, with developmental delays of varyin...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,多中心研究
doi：10.1007/s10545-017-0033-7
更新日期：2017-05-01 00:00:00
abstract：:We report a 5-year-old child carrying polymerase gamma (POLG1) mutations, but strikingly normal oxidative phosphorylation analysis in muscle, fibroblasts and liver. Mutations in POLG1 have so far been described in children with severe combined oxidative phosphorylation (OXPHOS) deficiencies and with the classical Alpe...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-008-0871-4
更新日期：2008-12-01 00:00:00
abstract：:We report a new constellation of clinical features consisting of hypermanganesaemia, liver cirrhosis, an extrapyramidal motor disorder and polycythaemia in a 12 year-old girl born to consanguineous parents. Blood manganese levels were >3000 nmol/L (normal range <320 nmol/L) and MRI revealed signal abnormalities of the...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-008-0813-1
更新日期：2008-04-01 00:00:00
abstract：:We report studies of a Greek boy of gypsy origin that show that he has severe deficiency of glycine N -methyltransferase (GNMT) activity due to apparent homozygosity for a novel mutation in the gene encoding this enzyme that changes asparagine-140 to serine. At age 2 years he was found to have mildly elevated serum li...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/B:BOLI.0000009978.17777.33
更新日期：2003-01-01 00:00:00
abstract：:We are constantly exposed to sources of agents that directly damage the genetic material. This exposure comes from environmental sources but also from within our own organisms. DNA damage occurs at a high frequency due to metabolic processes and environmental factors such as various exposures and the intake of food an...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1023/a:1015681929316
更新日期：2002-05-01 00:00:00
abstract：:The activity (mean +/- SD) of galactose-1-phosphate uridyl transferase in two long-term lymphoid cell lines from Caucasian patients with transferase deficiency galactosaemia, a heterozygote, and eight normal subjects was 0, 78 and 168 +/- 55 nmol UDPG consumed (mg protein)-1h-1, respectively. Also, no activity was fou...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01799977
更新日期：1987-01-01 00:00:00
abstract：:There is now strong evidence for the implication of collagen alpha 1(I), alpha 2(I) and alpha 1(III) mutations in many forms of osteogenesis imperfecta and inherited arterial aneurysms (Ehlers Danlos syndrome type IV). A sizeable proportion of these disorders have detectable abnormalities by conventional protein chemi...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/BF01799292
更新日期：1989-01-01 00:00:00
abstract：:Carnitine palmitoyltransferase type II (CPT II) deficiency has three basic phenotypes, late-onset muscular (mild), infantile/juvenile hepatic (intermediate) and severe neonatal. We have measured fatty acid oxidation and CPT II activity and performed mutation studies in 24 symptomatic patients representing the full cli...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/a:1025947930752
更新日期：2003-01-01 00:00:00
abstract：:Glycogen storage disease type I (GSD I) is characterized by impaired production of glucose from glycogenolysis and gluconeogenesis resulting in severe fasting hypoglycaemia. The aim of the present study was to examine the efficacy of a continuous subcutaneous glucose monitoring system (CGMS MiniMed), to determine the ...
journal_title：Journal of inherited metabolic disease
pub_type： 临床试验,杂志文章
doi：10.1023/a:1013996325720
更新日期：2001-12-01 00:00:00
