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 trifunctional protein (MTP). Secondly, the introduction of tandem MS for the analysis of plasma acylcarnitines has greatly facilitated the identification of patients with a defect in fatty acid oxidation (FAO). These two developments explain why the number of defined FAO disorders has increased dramatically, making FAO disorders the most rapidly growing group of inborn errors of metabolism. In this review we describe the current state of knowledge of the enzymes involved in the mitochondrial oxidation of straight-chain, branched-chain and (poly)unsaturated fatty acyl-CoAs as well as disorders of fatty acid oxidation. The laboratory diagnosis of these disorders is described, with particular emphasis on the methods used to identify the underlying enzyme defect and the molecular mutations. In addition, a simple flowchart is presented as a guide to the identification of mitochondrial FAO-disorders. Finally, treatment strategies are discussed briefly.
journal_name
J Inherit Metab Disjournal_title
Journal of inherited metabolic diseaseauthors
Wanders RJ,Vreken P,den Boer ME,Wijburg FA,van Gennip AH,IJlst Ldoi
10.1023/a:1005504223140keywords:
subject
Has Abstractpub_date
1999-06-01 00:00:00pages
442-87issue
4eissn
0141-8955issn
1573-2665journal_volume
22pub_type
杂志文章,评审abstract：BACKGROUND:One major problem of using hypercholesterolaemia alone as a primary criterion for diagnosing familial hypercholesterolaemia (FH) is that 15-40% of relatives may be misdiagnosed because plasma lipid levels in FH heterozygotes overlap with those in the general population. SETTING:General Hospital/University o...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-007-0563-5
更新日期：2007-04-01 00:00:00
abstract：:Defects in a pathway as complex as the electron transport chain cause a variety of clinical abnormalities, which vary from fatal lactic acidosis in infancy to mild muscle disease in adults. The primary defect may reside in the nucleus or the mitochondrial genome. Until relatively recently, biochemical assays were the ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/BF01799107
更新日期：1996-01-01 00:00:00
abstract：:Methylmalonate (MMA) accumulates in the tissues of patients with methylmalonic acidaemia, who present severe neurological signs soon after birth and later mental retardation. Attempting to understand the pathophysiology of the disorder, we investigated the effects of MMA on brain glucose uptake, lactate release and CO...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01800350
更新日期：1992-01-01 00:00:00
abstract：:Transaldolase (TAL) is an enzyme in the pentose phosphate pathway (PPP) that generates NADPH for protection against oxidative stress. While deficiency of other PPP enzymes, such as transketolase (TKT), are incompatible with mammalian cell survival, mice lacking TAL are viable and develop progressive liver disease attr...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1002/jimd.12197
更新日期：2020-05-01 00:00:00
abstract：:At present, there is just one approved therapy for patients with mitochondrial diseases in Europe, another in Japan, and none in the United States. These facts reveal an important and significant unmet need for approved therapies for these debilitating and often fatal disorders. To fill this need, it is critical for c...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1002/jimd.12353
更新日期：2020-12-24 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：: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：:6-Methyluracil (6MU) has been identified in urine collected during acute illness in two children with beta-ketothiolase deficiency (approximately 1 mmol/L) and in two children with recurrent infection-related ketoacidaemia of unknown aetiology (levels of 6.3 and 7.1 mmol/mmol creatinine). Significant amounts of 6MU we...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF00735400
更新日期：1994-01-01 00:00:00
abstract：:Urea cycle disorders often present as devastating metabolic conditions, resulting in high mortality and significant neuropsychological damage, despite treatment. The Urea Cycle Disorders Longitudinal Study is a natural history study that collects data from regular clinical follow-up and neuropsychological testing. Thi...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-017-0132-5
更新日期：2018-07-01 00:00:00
abstract：:Glycogen storage disease type Ib (GSD-Ib) is caused by a deficiency in the ubiquitously expressed glucose-6-phosphate (G6P) transporter (G6PT or SLC37A4). The primary function of G6PT is to translocate G6P from the cytoplasm into the lumen of the endoplasmic reticulum (ER). Inside the ER, G6P is hydrolyzed to glucose ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/s10545-018-0180-5
更新日期：2018-11-01 00:00:00
abstract：:To date, inborn errors of neurotransmitters have been defined based on the classic concept of inborn error of metabolism (IEM), and they include defects in synthesis, catabolism, and transport pathways. However, the omics era is bringing insights into new diseases and is leading to an extended definition of IEM includ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/s10545-018-0235-7
更新日期：2018-11-01 00:00:00
abstract：:A sensitive and selective analytical technique is described for the determination of N-acetylaspartic acid in body fluids using stable isotope dilution in combination with positive chemical ionization mass spectrometry with selected ion monitoring. Control mean and ranges have been established: in urine 19.5 and 6.6-3...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01799929
更新日期：1991-01-01 00:00:00
abstract：:A biomarker is an analyte indicating the presence of a biological process linked to the clinical manifestations and outcome of a particular disease. In the case of lysosomal storage disorders (LSDs), primary and secondary accumulating metabolites or proteins specifically secreted by storage cells are good candidates f...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/s10545-011-9308-6
更新日期：2011-06-01 00:00:00
abstract：:We analysed the gene of the human alpha-subunit of liver phosphorylase kinase (PHKA2) in four Japanese families with X-linked liver phosphorylase kinase deficiency type 1 by RT-PCR followed by PCR-single-strand conformation polymorphism and direct DNA sequencing. In this study, two novel mutations (Y116D and 2675A-->G...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/a:1005422819207
更新日期：1998-12-01 00:00:00
abstract：:This study aimed to evaluate systematically the effect of the free use of fruits and vegetables containing an intermediate amount of phenylalanine (51-100 mg/100 g) on the biochemical control in children with phenylketonuria (PKU). Fifteen subjects with PKU, with a median age of 6 years (range 1-24 years) were studied...
journal_title：Journal of inherited metabolic disease
pub_type： 临床试验,杂志文章
doi：10.1023/a:1025150901439
更新日期：2003-01-01 00:00:00
abstract：:The progress and extent of myelination can be assessed using magnetic resonance imaging (MRI). Myelination is delayed or diminished in several inherited metabolic abnormalities presenting in early life. Only minimal myelination of the CNS occurs in Pelizaeus-Merzbacher disease. Dysmyelination tends to produce fairly s...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/BF00711909
更新日期：1993-01-01 00:00:00
abstract：:Investigations into the biochemical markers associated with executive function (EF) impairment in children with early and continuously treated phenylketonuria (ECT-PKU) remain largely phenylalanine-only focused, despite experimental data showing that a high phenylalanine:tyrosine (phe:tyr) ratio is more strongly assoc...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,多中心研究
doi：10.1007/s10545-010-9211-6
更新日期：2010-12-01 00:00:00
abstract：:We report D-2-hydroxyglutaric aciduria in a neonate with intracranial haemorrhage and absence of the corpus callosum. D-2-hydroxyglutaric acid was confirmed by specific chiral derivatization gas chromatography-mass spectrometry. Absence of the corpus callosum and spontaneous neonatal intracranial haemorrhage should ra...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/a:1024000202364
更新日期：2003-01-01 00:00:00
abstract：:Sandhoff disease is caused by the defective activity of the lysosomal enzyme beta-hexosaminidase, resulting in accumulation of the glycolipids, GA2 and GM2. Niemann-Pick A/B disease is caused by the defective activity of lysosomal acid sphingomyelinase resulting in sphingomyelin accumulation. Pulmonary complications h...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/b:boli.0000042958.22066.6c
更新日期：2004-01-01 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：: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：: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：:Patients with Fabry disease frequently develop left ventricular (LV) hypertrophy and renal fibrosis. Due to heat intolerance and an inability to sweat, patients tend to avoid exposure to sunlight. We hypothesized that subsequent vitamin D deficiency may contribute to Fabry cardiomyopathy. This study investigated the v...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-013-9653-8
更新日期：2014-03-01 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：:An adult patient with hereditary tyrosinaemia type I who developed renal failure is reported. She received a renal transplant at the age of 23 years. In childhood her kidney disease was dominated by multiple tubular defects with resulting hypophosphataemic rickets. Metabolic acidosis was the most prominent feature in ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01804389
更新日期：1991-01-01 00:00:00
abstract：:Inborn errors of purine metabolism exhibit broad neurological, immunological, haematological and renal manifestations. Limited awareness of the phenotypic spectrum, the recent descriptions of newer disorders and considerable genetic heterogeneity, have contributed to long diagnostic odysseys for affected individuals. ...
journal_title：Journal of inherited metabolic disease
pub_type：
doi：10.1007/s10545-014-9731-6
更新日期：2014-09-01 00:00:00
abstract：:Adult-onset glycogen storage disease type II (GSD II) (McKusick 232300) is a progressive disabling myopathy. At present there is no treatment of proven clinical efficacy. Enzyme replacement therapy may in the future provide benefit but it will be costly and is not yet freely available. L-Alanine, a simple and relative...
journal_title：Journal of inherited metabolic disease
pub_type： 临床试验,杂志文章
doi：10.1007/s10545-006-0238-7
更新日期：2006-02-01 00:00:00
abstract：:The intestinal microvillar enzyme complex sucrase-isomaltase has been studied in cystic fibrosis and control ileum. A number of biochemical parameters of the enzyme in ileum homogenates have been determined. Both solubilized as well as membrane-bound sucrase-isomaltase were analyzed with respect to their reaction with...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01805427
更新日期：1985-01-01 00:00:00
abstract：BACKGROUND:Maple syrup urine disease (MSUD) is a rare disease that requires a protein-restricted diet for successful management. Little is known, however, about the psychosocial outcome of MSUD patients. This study investigates the relationship between metabolic and clinical parameters and psychosocial outcomes in a co...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-017-0083-x
更新日期：2017-11-01 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
