Abstract：
:What next? The Human Genome Project signifies complexity rather than simplification in the relationship between genotype and phenotype. Genotypes are embedded in genomes. Individuality in phenotypes is embedded in components of the phenome (transcriptome, metabolome, proteome, etc.). The phenome, its layers, and its nodes, links and networks, require elucidation; there is a need for a Human Phenome Project (Freimer and Sabatti 2003). Biology has largely been a reductive science in the recent past; integrative biology lies ahead. Clinician-scientists (including human biochemical geneticists) will be recognized as key participants in the 'medical' Phenome Project as it reveals components of individuality, and their contributions, in simple or combinatorial fashion, to Mendelian and complex traits; better ways to treat 'genetic disease' will be by-products of the project. Although the Word is common to all, most men live as if each had a private wisdom of his own.Herakleitos
journal_name
J Inherit Metab Disjournal_title
Journal of inherited metabolic diseaseauthors
Scriver CRdoi
10.1023/B:BOLI.0000031100.26546.6ekeywords:
subject
Has Abstractpub_date
2004-01-01 00:00:00pages
305-17issue
3eissn
0141-8955issn
1573-2665pii
5268029journal_volume
27pub_type
杂志文章,评审abstract：:The immunochemical analysis of enzyme from mucopolysaccharidoses (MPS) patients is aimed at defining the level and nature of the enzymically deficient protein produced by specific gene mutations. Immunochemical techniques allow purification of enzyme, characterization of the composite molecular species, measurement of...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/BF00711309
更新日期：1993-01-01 00:00:00
abstract：:Eighty-nine protein-loading tests were performed in 80 patients with an increased blood phenylalanine concentration. The amount of protein corresponding to 0.18 g phenylalanine/kg body weight per day was calculated and given for 3 days, during which time eight phenylalanine and eight tyrosine blood concentrations were...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01799751
更新日期：1982-01-01 00:00:00
abstract：:In many European countries neonatal screening has been introduced over the last 50 years as an important public health programme. Depending on health care structure, available funds, local politics, input from professional groups, parent groups, and the general public this introduction has led to different approaches ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-012-9483-0
更新日期：2012-07-01 00:00:00
abstract：:The pathogenesis of brain dysfunction in phenylketonuria (PKU) is still under investigation. Hyperphenylalaninaemia results in increased turnover of myelin. In order to demonstrate the derangement of myelinization in PKU we studied the visual evoked potentials (VEP) in 14 PKU patients and in 20 normal subjects. VEP fi...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01800430
更新日期：1988-01-01 00:00:00
abstract：:Our series of studies on Hunter disease in Japanese patients showed allelic heterogeneity of IDS gene mutations, genotype/phenotype correlation and racial differences in distribution of mutations. Twenty-five different small mutations have been characterized. Small mutations in the Japanese population are widely distr...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/a:1005363414792
更新日期：1998-02-01 00:00:00
abstract：:We present a 32-year-old patient who, from age 7 months, developed photophobia, left-eye ptosis and progressive muscular weakness. At age 7 years, she showed normal psychomotor development, bilateral ptosis and exercise-induced weakness with severe acidosis. Basal blood and urine lactate were normal, increasing dramat...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-010-9169-4
更新日期：2010-12-01 00:00:00
abstract：:Alkaptonuria (AKU) is a rare genetic disease that affects the entire joint. Current standard of AKU treatment is palliative and little is known about its physiopathology. Neovascularization is involved in the pathogenesis of systemic inflammatory rheumatic diseases, a family of related disorders that includes AKU. Her...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-016-9976-3
更新日期：2016-11-01 00:00:00
abstract：:Glycine encephalopathy, or nonketotic hyperglycinaemia (NKH; Mckusick 238300) is a severe autosomal recessive disease due to a defect in the glycine cleavage system (GCS), which is a complex of four subunits: P-, T-, H- and L-proteins. A P-protein (glycine decarboxylase or GLDC) deficiency was reported in about 80% of...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-006-0202-6
更新日期：2006-02-01 00:00:00
abstract：:In mammals, dosage compensation for X-linked genes between males and females is achieved by the inactivation of one of the X chromosomes in females. The inactivation event occurs early in development in all cells of the female mouse embryo and is stable and heritable in somatic cells. However, in the primordial germ c...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/BF01799608
更新日期：1992-01-01 00:00:00
abstract：:Aspartylglycosaminuria (AGU) is a lysosomal storage disease caused by deficient activity of glycosylasparaginase (AGA), and characterized by motor and mental retardation. Enzyme replacement therapy (ERT) in adult AGU mice with AGA removes the accumulating substance aspartylglucosamine from and reverses pathology in ma...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-010-9158-7
更新日期：2010-10-01 00:00:00
abstract：:High lactate concentrations occur in type I glycogen storage disease (GSD) whenever glycogenolysis occurs. Not only does hyperlactataemia cause acute clinical deterioration, but chronic lactate elevations have also been associated with many of the long-term complications in GSD. A portable finger-stick blood lactate m...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-005-0090-1
更新日期：2005-01-01 00:00:00
abstract：:Mixed hyperlipidaemia is a common finding in glycogen storage disease type Ia (GSD Ia). Although cross-sectional studies have demonstrated increases in intermediate-density lipoproteins (IDLs) and reductions in lipoprotein lipase activity, no studies have investigated the dynamics of apolipoprotein B-100 (apo B) metab...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/a:1012407609063
更新日期：2001-10-01 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：:There is a failure of growth in hypoxanthine guanine phosphoribosyltransferase deficiency; slow weight gain is marked after the second year of age but is apparent in the birth weights of all eight of our patients for whom we have data. However, head growth and bone development are less affected than weight. A partial ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01800063
更新日期：1987-01-01 00:00:00
abstract：:Detailed biochemical studies have been carried out in a female heterozygote for ornithine carbamoyl-transferase (OCT) deficiency. Increased levels of the pyrimidines, orotic acid, uridine and uracil, were observed in plasma as well as urine by utilizing an adaptation of high performance liquid chromatography (HPLC). U...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF02263578
更新日期：1981-01-01 00:00:00
abstract：:Interest in newborn screening (NBS) for lysosomal storage disorders (LSDs) has increased significantly due to newly developed enzyme replacement therapy (ERT), the need for early diagnosis, and advances in technical developments. Since the central nervous system cannot be treated by ERT, neuronopathic LSDs are general...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/s10545-010-9130-6
更新日期：2010-08-01 00:00:00
abstract：:For over two decades, nitisinone (NTBC) has been successfully used to manipulate the tyrosine degradation pathway and save the lives of many children with hereditary tyrosinaemia type 1. More recently, NTBC has been used to halt homogentisic acid accumulation in alkaptonuria (AKU) with evidence suggesting its efficacy...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1002/jimd.12229
更新日期：2020-09-01 00:00:00
abstract：:The implementation of whole-exome sequencing in clinical diagnostics has generated a need for functional evaluation of genetic variants. In the field of inborn errors of metabolism (IEM), a diverse spectrum of targeted biochemical assays is employed to analyze a limited amount of metabolites. We now present a single-p...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-017-0131-6
更新日期：2018-05-01 00:00:00
abstract：:Acute intermittent porphyria (AIP) caused by mutations in the hydroxymethylbilane synthase gene (HMBS), has been reported in almost all human populations, with varying frequencies. A founder effect for a few specific mutations in geographic regions where prevalence is high (Sweden, The Netherlands, Switzerland) has be...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-010-9228-x
更新日期：2010-12-01 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：:Menkes disease (MNK) is a lethal, X-linked recessive disorder of copper metabolism dominated by neurodegenerative symptoms and connective tissue disturbances. The incidence of MNK in Asia is not known. Most patients die by the age of 3 years if adequate treatment is not carried out. Early parenteral administration of ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-005-0473-3
更新日期：2005-01-01 00:00:00
abstract：:5-Oxoprolinuria is primarily associated with inborn errors of the gamma-glutamyl cycle. In addition, transient 5-oxoprolinuria has been reported to occur in a variety of conditions, such as prematurity and malnutrition, and during medication. We report an unusual case of permanent 5-oxoprolinuria. The patient presente...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-006-0370-4
更新日期：2006-08-01 00:00:00
abstract：:2-Methyl-3-hydroxybutyryl-CoA dehydrogenase (EC 1.1.1.178) deficiency is a recently described defect of isoleucine catabolism. The disorder is characterized by normal early development followed by a progressive loss of mental and motor skills. Deterioration may be rapid or may follow a slower decline with a possible s...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/a:1021251202287
更新日期：2002-10-01 00:00:00
abstract：:Twin brothers were born with clinical symptoms indicating that they were suffering from Zellweger syndrome. However, instead of a generalized peroxisomal dysfunction, only very long-chain fatty acids and the pristanic acid/phytanic acid ratio were elevated in plasma and decreased oxidation of very long-chain fatty aci...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/a:1005318308422
更新日期：1997-09-01 00:00:00
abstract：:In most patients with deficiency of tetrahydrobiopterin (BH4) continuous administration of BH4 or of a synthetic analogue such as 6-methyltetrahydropterin (6-MPH4) lowers plasma phenylalanine concentrations to the therapeutic range. The effective dose of BH4 varies from 1 to 2 mg kg-1 daily in patients with defective ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01800658
更新日期：1985-01-01 00:00:00
abstract：:Carnitine palmitoyltransferase type I (CPT I) is unique among long-chain fatty acid oxidation enzymes in that there are two tissue-specific isoforms, 'hepatic' and 'muscle', which are encoded by two separate genes. The 'hepatic' isoform is expressed in liver, kidney and fibroblasts and at low levels in the heart, whil...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/a:1005694320063
更新日期：2001-02-01 00:00:00
abstract：:In recent years tremendous progress has been made with respect to the enzymology of the mitochondrial fatty acid beta-oxidation machinery and defects therein. Firstly, a number of new mitochondrial beta-oxidation enzymes have been identified, including very-long-chain acyl-CoA dehydrogenase (VLCAD) and mitochondrial t...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1023/a:1005504223140
更新日期：1999-06-01 00:00:00
abstract：BACKGROUND:Methylmalonic acidemia and intracellular cobalamin metabolism disorders represent a heterogeneous group of inborn errors of metabolism. Most patients will require diagnostic and/or therapeutic procedures frequently requiring sedation or anesthetic management due to neurological and neurocognitive impairments...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/s10545-015-9816-x
更新日期：2015-09-01 00:00:00
abstract：:Cystathionine beta synthase (CBS) deficiency is a recessive inborn error of metabolism characterized by elevated serum total homocysteine (tHcy). Betaine supplementation, which can lower tHcy by stimulating homocysteine remethylation to methionine, is often given to CBS deficient patients in combination with other tre...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-015-9883-z
更新日期：2016-01-01 00:00:00
abstract：:The substrate O-(alpha-L-idopyranosyluronic acid-2-sulphate)-(1 leads to 4)-2,5-anhydro-D-(3H-1) mannitol-6-sulphate was used at a final concentration of 50 mmol/l to measure the alpha-L-idurono-2-sulphate sulphatase activities of cell extracts, serum and amniotic fluid. Activities were measured after dialysis against...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01800738
更新日期：1983-01-01 00:00:00
