Abstract:
UNLABELLED:In pilot studies of the usefulness of solid state nuclear magnetic resonance spectroscopy in characterizing chemical and molecular structural effects of alkaptonuria on connective tissue, we have obtained (13) C spectra from articular cartilage from an AKU patient. An apparently normal anatomical location yielded a cross polarization magic angle spinning spectrum resembling literature spectra and dominated by collagen and glycosaminoglycan signals. All spectral linewidths from strongly pigmented ochronotic cartilage however were considerably increased relative to the control indicating a marked increase in collagen molecular disorder. This disordering of cartilage structural protein parallels, at the atomic level, the disordering revealed at higher length scales by microscopy. We also demonstrate that the abnormal spectra from ochronotic cartilage fit with the abnormality in the structure of collagen fibres at the ultrastructural level, whereby large ochronotic deposits appear to alter the structure of the collagen fibre by invasion and cross linking. SUMMARY:Increased signal linewidths in solid state NMR spectra of ochronotic articular cartilage from an AKU patient relative to linewidths in normal, control, cartilage reveals a marked decrease in collagen molecular order in the diseased tissue. This atomic level disordering parallels higher length scale disorder revealed by microscopic techniques.
journal_name
J Inherit Metab Disjournal_title
Journal of inherited metabolic diseaseauthors
Chow WY,Taylor AM,Reid DG,Gallagher JA,Duer MJdoi
10.1007/s10545-011-9373-xsubject
Has Abstractpub_date
2011-12-01 00:00:00pages
1137-40issue
6eissn
0141-8955issn
1573-2665journal_volume
34pub_type
杂志文章abstract::We examined the value of the fasting plasma phenylalanine/tyrosine ratio obtained in an ordinary clinical setting for assessing the probability of being a heterozygote for hyperphenylalaninaemia. This biochemical test was found to be of little value in those with a high (66%) prior risk of heterozygosity, because it c...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF00711323
更新日期:1993-01-01 00:00:00
abstract::The mitochondrial myopathies or encephalomyopathies with known biochemical defects can be divided into 5 groups: (1) defects of mitochondrial transport, such as CPT deficiency or carnitine deficiencies; (2) defects of substrate utilization, such as PDHC deficiency or defects of beta-oxidation; (3) defects of the Krebs...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1007/BF01812852
更新日期:1987-01-01 00:00:00
abstract::This workshop was organized as a direct response to concerns and queries raised by laboratory personnel, both in Europe and in the United States, about the imminent withdrawal of Beckman Coulter from the amino acid analysis market. The topics covered included external quality control schemes, standard operating proced...
journal_title:Journal of inherited metabolic disease
pub_type:
doi:10.1023/a:1010343707174
更新日期:2001-04-01 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::Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is an autosomal recessive lysosomal storage disorder resulting from a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS) activity. Diagnosis can be challenging and requires agreement of clinical, radiographic, and laboratory findings. A group of bioc...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-013-9587-1
更新日期:2013-03-01 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::In three untreated patients with phenylketonuria (PKU), three PKU and six hyperphenylalaninaemic (HPA) patients in good metabolic control, the kinetic constants of platelet in vitro uptake of [14C]serotonin (5HT) did not significantly differ from those in 12 control subjects matched for age. The platelet concentration...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF01800371
更新日期:1988-01-01 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::Ten of 31 patients with steroid sulphatase (STS) deficiency were found to have an allergic disease (bronchial asthma, allergic rhinitis, or atopic dermatitis). STS deficiency may predispose patients to allergic disease. ...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1023/a:1005375902993
更新日期:1997-11-01 00:00:00
abstract::Defects of the mitochondrial oxidative phosphorylation (OXPHOS) system are frequent causes of neurological disorders in children. Linkage analysis and DNA sequencing identified a new founder p.G250V substitution in the C20ORF7 complex I chaperone in five Ashkenazi Jewish patients from two families with a combined OXPH...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-011-9348-y
更新日期:2012-01-01 00:00:00
abstract::Recently a striking elevation of the activity of chitotriosidase, an endo beta-glucosaminidase distinct from lysozyme, was found in plasma from patients with Gaucher type I disease (McKusick 230800). Plasma chitotriosidase originates from activated macrophages and this elevation is secondary to the basic defect in Gau...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF02436762
更新日期:1995-01-01 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::Organic acidurias represent a group of inherited disorders resulting from deficient activity of specific enzymes of the catabolism of amino acids, carbohydrates or lipids, leading to tissue accumulation of one or more carboxylic (organic) acids. Patients affected by organic acidurias predominantly present neurological...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1023/B:BOLI.0000037353.13085.e2
更新日期:2004-01-01 00:00:00
abstract::A striking elevation of plasma chitotriosidase activity, greater than 150 times the normal median value, was found in two galactosialidosis patients. Furthermore, increased plasma chitotriosidase activity, 10-53 times the normal median value, was also observed in fucosidosis, glycogen storage disease type IV, Alagille...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1023/b:boli.0000043025.17721.fc
更新日期:2004-01-01 00:00:00
abstract::Wilson disease (WD) is an autosomal recessive disorder of copper accumulation leading to liver and/or brain damage. In this paper, we describe the results of a pilot study of screening for WD using ceruloplasmin determinations in dried blood samples. Specimens were collected from children aged 1 to 6 years who were se...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1023/a:1005455401076
更新日期:1999-02-01 00:00:00
abstract::A 5-year-old boy, excreting large amounts of 2-hydroxyglutaric acid in the urine (3.3-7.6 mmol/l), is described. The patient presented with psychomotor retardation and dystrophy. His skeletal age was delayed. The EEG was not well differentiated; it resembled that observed in 2-year-old children. There was a severe ana...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF02312543
更新日期:1980-01-01 00:00:00
abstract::Patients with an inborn error of metabolism (IEM) are deficient of an enzyme involved in metabolism, and as a consequence metabolism reprograms itself to reach a new steady state. This new steady state underlies the clinical phenotype associated with the deficiency. Hence, we need to know the flux of metabolites throu...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1007/s10545-017-0124-5
更新日期:2018-05-01 00:00:00
abstract::Latin America includes more than 40 countries and possessions, and its population of 570 million has an important representation of the three main human races. The area is experiencing an economic improvement, progressively bringing the inborn errors of metabolism (IEM) to a higher level among health priorities. Chall...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-010-9112-8
更新日期:2010-10-01 00:00:00
abstract:OBJECTIVES:To study the incidence of galactosaemia in the state of São Paulo and the benefit/cost (B/C) ratio of the introduction of neonatal screening for galactosaemia, comparing it with a selective approach. METHODS:An enzymatic-colorimetric assay was used for the screening of total galactose (TG) in a sample of 10...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-009-1112-1
更新日期:2009-12-01 00:00:00
abstract::Low-density lipoprotein receptor (LDLR) is a cell-surface glycoprotein that mediates specific uptake and catabolism of plasma LDL. Mutations located in the coding region of the LDLR gene affect the structure and function of the protein and cause familial hypercholesterolaemia (FH). Mutations in the regulatory regions ...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1023/B:BOLI.0000037337.93335.c4
更新日期:2004-01-01 00:00:00
abstract::We measured L-ornithine oxidation in cultured skin fibroblasts from seven patients with hyperornithinaemia-hyperammonaemia-homocitrullinuria (HHH) syndrome (McKusick 23897), and compared it with oxidation by ornithine aminotransferase deficient gyrate atrophy (McKusick 25887) cells and lysinuric protein intolerance (M...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF01805528
更新日期:1989-01-01 00:00:00
abstract::Carnitine uptake has been studied in fibroblasts from a case of hereditary carnitine deficiency and in relatives. There was no evidence for carrier-dependent uptake in cells from the patient. The mother and probably the healthy sister had an impaired uptake. The results show that the defect in this form of carnitine d...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF01800711
更新日期:1989-01-01 00:00:00
abstract::A family of Maltese dogs with malonic aciduria is reported. The propositus presented at 3 years of age with episodes of seizures and stupor with hypoglycaemia, acidosis, and ketonuria. Urinary organic acid assays showed elevated malonic acid without elevation of methylmalonic acid. Cultured fibroblasts had normal malo...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1023/a:1005635306257
更新日期:1999-12-01 00:00:00
abstract:OBJECTIVE:There is an urgent need for reliable and universally applicable outcome measures for children with mitochondrial diseases. In this study, we aimed to adapt the currently available Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) to the International Paediatric Mitochondrial Disease Scale (IPMDS) durin...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,多中心研究
doi:10.1007/s10545-016-9948-7
更新日期:2016-09-01 00:00:00
abstract::Hyperhomocysteinaemia is an independent risk factor for cardiovascular disease. The C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) is a common genetic cause of increased homocysteine (HCY) levels. Post-methionine-load HCY concentrations allow identification of certain cases of hyperhomocysteinaemia ...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1023/a:1005513626542
更新日期:1999-06-01 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::Hexosaminidase A activities were determined in tears and peripheral leukocytes of carriers and noncarriers for Tay-Sachs Disease (TSD) as a percentage of total hexosaminidase activity. Correlation between enzyme activities in tears and leukocytes was highly significant (r = 0.75, p less than 0.01). Compared to leukocy...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF01805619
更新日期:1984-01-01 00:00:00
abstract::Animal models of inborn errors of metabolism are useful for investigating the pathogenesis associated with the corresponding human disease. Since the mechanisms involved in the pathophysiology of succinate semialdehyde dehydrogenase (SSADH) deficiency (Aldh5a1; OMIM 271980) are still not established, in the present st...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-007-0599-6
更新日期:2007-10-01 00:00:00
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::Creatine transporter deficiency was discovered in 2001 as an X-linked cause of intellectual disability characterized by cerebral creatine deficiency. This review describes the current knowledge regarding creatine metabolism, the creatine transporter and the clinical aspects of creatine transporter deficiency. The cond...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1007/s10545-014-9713-8
更新日期:2014-09-01 00:00:00