Abstract:
:Rapid diagnosis and early specific treatment of metabolic epilepsies due to inborn errors of metabolism (IEMs) is crucial to avoid irreversible sequalae. Nowadays, besides the profile analysis of amino- and organic acids, a range of additional targeted assays is used for the selective screening of those diseases. This strategy can lead to long turn-around times, repeated sampling and diagnostic delays. To replace those individual targeted assays, we developed a new liquid chromatography mass spectrometry method (LC-MS/MS) for the differential diagnosis of inherited metabolic epilepsies that are potentially treatable. The method was developed to simultaneously quantify 12 metabolites (sulfocysteine, guanidinoacetate, creatine, pipecolic acid, Δ1 -piperideine-6-carboxylate (P6C), proline, Δ1 -pyrroline-5-carboxylate (P5C), and the B6 -vitamers) enabling the diagnosis of nine different treatable IEMs presenting primarily with early-onset epilepsy. Plasma and urine samples were mixed with internal standards, precipitated and the supernatants were analyzed by LC-MS/MS. In comparison with previous assays, no derivatization of the metabolites is necessary for analysis. This LC-MS method was validated for quantitative results for all metabolites except P6C and P5C for which semiquantitative results were obtained due to the absence of commercially available standards. Coefficients of variation for all analytes were below 15% and recovery rates range between 80% and 120%. Analysis of patient samples with known IEMs demonstrated the diagnostic value of the method. The presented assay covers a selected panel of biochemical markers, improves the efficiency in the laboratory, and potentially leads to faster diagnoses and earlier treatment avoiding irreversible damage in patients affected with IEMs.
journal_name
J Inherit Metab Disjournal_title
Journal of inherited metabolic diseaseauthors
Mathis D,Beese K,Rüegg C,Plecko B,Hersberger Mdoi
10.1002/jimd.12244subject
Has Abstractpub_date
2020-09-01 00:00:00pages
1102-1111issue
5eissn
0141-8955issn
1573-2665journal_volume
43pub_type
杂志文章abstract::A new French-Canadian family from the province of Quebec is reported, in which a male child was diagnosed as hyperargininaemic after showing positive tests for cystinuria on neonatal screening. The child has no residual activity of erythrocyte arginase, and a plasma arginine level of 633 mumol/l. Both parents have 32-...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF02310878
更新日期:1983-01-01 00:00:00
abstract::In a few rare diseases, specialised studies in cerebrospinal fluid (CSF) are required to identify the underlying metabolic disorder. We aimed to explore the possibility of detecting key synaptic proteins in the CSF, in particular dopaminergic and gabaergic, as new procedures that could be useful for both pathophysiolo...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-010-9256-6
更新日期:2011-04-01 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::Plasma total homocysteine (tHcy) determination is used in the diagnosis of homocystinuria, in cobalamin and folate deficiency and in cardiovascular risk assessment. However, determination of tHcy includes many pitfalls which complicate the assessment of homocysteine status. In the present article, we review basic know...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1023/a:1005321225893
更新日期:1997-06-01 00:00:00
abstract::Previous research has documented white matter abnormalities in the brains of individuals with early-treated phenylketonuria (ETPKU). The majority of these past studies have relied on a region-based approach which focused on a limited number of spatially-defined regions within the brain. In the present study, we used d...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-013-9650-y
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:BACKGROUND:Hearing loss (HL) is a well-known feature of Fabry disease (FD). Its presence and characteristics have mainly been studied in adult patients, while only limited data are available on the presence and degree of HL in children with FD. This prompted us to study hearing sensitivity in pediatric FD patients. ME...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-017-0051-5
更新日期:2017-09-01 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::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::A severely mentally retarded infant with congenital lactic acidosis due to pyruvate carboxylase deficiency is reported. The patient suffered from vomiting and convulsions soon after birth and developed severe mental and motor retardation at 3 months of age. The persistent elevation of pyruvate and lactate in both bloo...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF01800730
更新日期:1983-01-01 00:00:00
abstract::Enzyme defects in the mitochondrial fatty acid oxidation (FAO) are a large family of inherited metabolic disease well characterized clinically and genetically, but for which pharmacological strategies remain limited. It is now well established that regulation of genes involved in mitochondrial FAO is under control of ...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1007/s10545-008-0844-7
更新日期:2008-04-01 00:00:00
abstract::Early signs of renal dysfunction in glycogen storage disease type Ia (GSD Ia) are glomerular hyperfiltration and proteinuria. In a non-randomized study, the effect of captopril on the improvement of proteinuria in GSD Ia patients with microalbuminuria was investigated. A positive effect has been shown for the insulin-...
journal_title:Journal of inherited metabolic disease
pub_type: 临床试验,杂志文章
doi:10.1023/a:1005608113270
更新日期:2000-07-01 00:00:00
abstract::There is paucity of literature on dietary treatment in glycogen storage disease (GSD) type IV and formal guidelines are not available. Traditionally, liver transplantation was considered the only treatment option for GSD IV. In light of the success of dietary treatment for the other hepatic forms of GSD, we have initi...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1002/jimd.12339
更新日期:2020-12-17 00:00:00
abstract::Hawkinsinuria is a rare disorder of tyrosine metabolism that can manifest with metabolic acidosis and growth arrest around the time of weaning off breast milk, typically followed by spontaneous resolution of symptoms around 1 year of age. The urinary metabolites hawkinsin, quinolacetic acid, and pyroglutamic acid can ...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-016-9963-8
更新日期:2016-11-01 00:00:00
abstract:BACKGROUND:Fabry disease, an X-linked lysosomal storage disorder, leads to multi-organ dysfunction, including cerebrovascular disease and psychological disorders. However, the prevalence and pattern of associated cognitive dysfunction is not well understood. OBJECTIVES:To investigate whether there is reliable evidence...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s10545-013-9643-x
更新日期:2014-03-01 00:00:00
abstract::Congenital lactic acidoses form a heterogeneous group of disorders: this paper considers primarily defects of the pyruvate dehydrogenase complex and the respiratory chain. Attempts to treat these disorders are hampered by uncertainty concerning the pathophysiology and by the central role of the enzymes in cellular met...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1007/BF01799117
更新日期:1996-01-01 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
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::The congenital disorders of glycosylation (CDG) are inborn errors of metabolism with a great genetic heterogeneity. Most CDG are caused by defects in the N-glycan biosynthesis, leading to multisystem phenotypes. However, the occurrence of tissue-restricted clinical symptoms in the various defects in dolichol-phosphate...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1002/jimd.12095
更新日期:2019-09-01 00:00:00
abstract::Techniques for studying metabolic events in vivo in patients with inborn errors are reviewed. Loading or provocation tests that have been used widely are insensitive and frequently non-specific. Compounds labelled with stable isotopes can be used to study enzyme kinetics and substrate turnover, providing more detailed...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1007/BF01797925
更新日期:1991-01-01 00:00:00
abstract::Lesch-Nyhan disease (LND) is caused by complete deficiency of the hypoxanthine-guanine phosphoribosyltransferase enzyme. It is characterized by overproduction of uric acid, jointly with severe motor disability and self-injurious behaviour which physiopathology is unknown. These neurological manifestations suggest a dy...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-012-9470-5
更新日期:2012-11-01 00:00:00
abstract::Gonadal function was followed in 26 females and 12 males with galactosaemia due to deficiency of the enzyme galactose-1-phosphate (Gal-1-P) uridyl transferase over a 4 year period. Gonadal function was normal in males, but all females except two had evidence of acquired ovarian failure. Twelve females with ovarian fai...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF01799450
更新日期:1986-01-01 00:00:00
abstract::Niemann-Pick disease type C2 (NPC2) is caused by the inherited deficiency of a lysosomal cholesterol transport protein, NPC2 protein. Many cases of NPC2 present in early infancy with inflammatory lung disease, with subsequent severe neurological disease and death in early childhood. This disease is theoretically corre...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-010-9060-3
更新日期:2010-12-01 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::We present an update to the status of research on succinic semialdehyde dehydrogenase (SSADH) deficiency (SSADHD), a rare disorder of GABA metabolism. This is an unusual disorder featuring the accumulation of both GABA and its neuromodulatory analog, gamma-hydroxybutyric acid (GHB), and recent studies have advanced th...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1007/s10545-018-0153-8
更新日期:2018-07-01 00:00:00
abstract::Menkes disease (MD) is a neurodegenerative disorder characterized by a copper deficiency in the brain. It is caused by the defective intestinal absorption of copper resulting from a deficiency of a copper-transporting ATPase, ATP7A. This gives rise to an accumulation of copper in the intestine. The copper deficiency i...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-005-0150-6
更新日期:2005-01-01 00:00:00
abstract::A patient with a severe neonatal variant of 3-methylcrotonyl-CoA carboxylase (MCC) deficiency is reported. The first child of healthy consanguineous Turkish parents presented on the second day of life with dehydration, cyanosis, no sucking, generalized muscular hypotonia, encephalopathy, respiratory depression requiri...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-005-4559-8
更新日期:2005-01-01 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 retinal and neurological complications of abetalipoproteinaemia may be preventable by replacing vitamins A and E from an early age, but their role in adult presentations is less clear. Two adult females with abetalipoproteinaemia have received 8 and 10 years respectively of replacement therapy with vitamins A, E a...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF01799870
更新日期:1988-01-01 00:00:00
abstract::Current understanding of the means by which the trace metals copper, iron, and zinc are transported and stored in the human body is reviewed. Although metal-related inherited metabolic diseases manifest themselves as deficiencies in metalloenzymes, these deficiencies in fact arise from disturbances in the absorption/r...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF01811317
更新日期:1983-01-01 00:00:00