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[PMID]: 27940755
[Au] Autor:Tort F; Ugarteburu O; Torres MA; García-Villoria J; Girós M; Ruiz A; Ribes A
[Ad] Address:Secció d'Errors Congènits del Metabolisme-IBC, Servei de Bioquímica i Genètica Molecular, Hospital Clínic, IDIBAPS, CIBERER, Barcelona, Spain; and.
[Ti] Title:Lysine Restriction and Pyridoxal Phosphate Administration in a NADK2 Patient.
[So] Source:Pediatrics;138(5), 2016 Nov.
[Is] ISSN:1098-4275
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:We report the case of a 10-year-old Spanish girl with mutations in NADK2 Prenatal central nervous system abnormalities showed ventriculomegaly, colpocephaly, and hypoplasia of the corpus callosum. At birth, axial hypotonia, uncoordinated movements, microcephaly, and generalized cerebellar atrophy were detected. Metabolic investigations revealed high lysine, lactate, and pipecolic acid levels in blood and cerebrospinal fluid. Pyruvate carboxylase and pyruvate dehydrogenase activity in fibroblasts were normal. Beginning at birth she received biotin, thiamine, and carnitine supplementation. A lysine-restricted diet was started when she was 1 month old. Because pipecolic acid was high, pyridoxine was added to treatment. At 3 years old, astatic myoclonic epilepsy appeared, with no response to levetiracetam. We switched pyridoxine to pyridoxal phosphate, with electroclinical improvement. Because the activity of mitochondrial respiratory chain complexes III and IV was slightly low in muscle, other cofactors such as ubidecarenone, idebenone, vitamin E, and creatine were added to the treatment. At 8 years old, plasma acylcarnitine testing was performed, and high levels of 2-trans, 4-cis-decadienoylcarnitine were found. Whole exome sequencing identified a homozygous splice site mutation in NADK2 (c.956+6T>C; p.Trp319Cysfs*21). This substitution generates exon skipping, leading to a truncated protein. In fact, NADK2 messenger RNA and the corresponding protein were almost absent. Now, at 10 years of age she presents with ataxia and incoordination. She has oromotor dysphasia but is able to understand fluid language and is a very friendly girl. We hypothesize that the patient's clinical improvement could be due to her lysine-restricted diet together with cofactors and pyridoxal phosphate administration.
[Mh] MeSH terms primary: Diet
Hyperlysinemias/genetics
Lysine/administration & dosage
Mitochondrial Proteins/genetics
Mutation
Phosphotransferases (Alcohol Group Acceptor)/genetics
Pyridoxal Phosphate/therapeutic use
Vitamin B Complex/therapeutic use
[Mh] MeSH terms secundary: Child
Epilepsies, Myoclonic/genetics
Epilepsies, Myoclonic/therapy
Female
Homozygote
Humans
Lactic Acid/blood
Lactic Acid/cerebrospinal fluid
Lysine/blood
Lysine/cerebrospinal fluid
Mitochondrial Diseases/genetics
Nervous System Malformations/genetics
Pipecolic Acids/blood
Pipecolic Acids/cerebrospinal fluid
RNA, Messenger/metabolism
[Pt] Publication type:CASE REPORTS; JOURNAL ARTICLE
[Nm] Name of substance:0 (Mitochondrial Proteins); 0 (Pipecolic Acids); 0 (RNA, Messenger); 12001-76-2 (Vitamin B Complex); 33X04XA5AT (Lactic Acid); 5V5IOJ8338 (Pyridoxal Phosphate); EC 2.7.1.- (NADK2 protein, human); EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor)); H254GW7PVV (pipecolic acid); K3Z4F929H6 (Lysine)
[Em] Entry month:1706
[Cu] Class update date: 170622
[Lr] Last revision date:170622
[Js] Journal subset:AIM; IM
[Da] Date of entry for processing:161213
[St] Status:MEDLINE

  2 / 12 MEDLINE  
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[PMID]: 26980171
[Au] Autor:Leganés-Ramos A; Álvaro-Alonso EA; Martín de Rosales-Cabrera AM; Pérez-Encinas M
[Ad] Address:Servicio de Farmacia. Hospital Universitario Fundación Alcorcón (Madrid). alexlegaram@hotmail.com.
[Ti] Title:Oral formulation of pyridoxine for the treatment of pyridoxinedependent epilepsy in a paediatric patient.
[So] Source:Farm Hosp;40(2):131-3, 2016 Mar 01.
[Is] ISSN:0214-753X
[Cp] Country of publication:Spain
[La] Language:eng
[Mh] MeSH terms primary: Epilepsy/drug therapy
Hyperlysinemias/drug therapy
Pyridoxine/therapeutic use
Vitamin B Complex/therapeutic use
[Mh] MeSH terms secundary: Drug Compounding
Epilepsy/genetics
Female
Humans
Hyperlysinemias/genetics
Infant, Newborn
Pipecolic Acids/blood
Pipecolic Acids/urine
Pyridoxine/administration & dosage
Pyridoxine/chemistry
Vitamin B Complex/administration & dosage
Vitamin B Complex/chemistry
[Pt] Publication type:CASE REPORTS; JOURNAL ARTICLE
[Nm] Name of substance:0 (Pipecolic Acids); 12001-76-2 (Vitamin B Complex); H254GW7PVV (pipecolic acid); KV2JZ1BI6Z (Pyridoxine)
[Em] Entry month:1702
[Cu] Class update date: 170214
[Lr] Last revision date:170214
[Js] Journal subset:IM
[Da] Date of entry for processing:160317
[St] Status:MEDLINE
[do] DOI:10.7399/fh.2016.40.2.9233

  3 / 12 MEDLINE  
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[PMID]: 24847004
[Au] Autor:Houten SM; Denis S; Te Brinke H; Jongejan A; van Kampen AH; Bradley EJ; Baas F; Hennekam RC; Millington DS; Young SP; Frazier DM; Gucsavas-Calikoglu M; Wanders RJ
[Ad] Address:Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Department of Pediatrics, Emma Children's Hospital, Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, Box 1498, Ne
[Ti] Title:Mitochondrial NADP(H) deficiency due to a mutation in NADK2 causes dienoyl-CoA reductase deficiency with hyperlysinemia.
[So] Source:Hum Mol Genet;23(18):5009-16, 2014 Sep 15.
[Is] ISSN:1460-2083
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Dienoyl-CoA reductase (DECR) deficiency with hyperlysinemia is a rare disorder affecting the metabolism of polyunsaturated fatty acids and lysine. The molecular basis of this condition is currently unknown. We describe a new case with failure to thrive, developmental delay, lactic acidosis and severe encephalopathy suggestive of a mitochondrial disorder. Exome sequencing revealed a causal mutation in NADK2. NADK2 encodes the mitochondrial NAD kinase, which is crucial for NADP biosynthesis evidenced by decreased mitochondrial NADP(H) levels in patient fibroblasts. DECR and also the first step in lysine degradation are performed by NADP-dependent oxidoreductases explaining their in vivo deficiency. DECR activity was also deficient in lysates of patient fibroblasts and could only be rescued by transfecting patient cells with functional NADK2. Thus NADPH is not only crucial as a cosubstrate, but can also act as a molecular chaperone that activates and stabilizes enzymes. In addition to polyunsaturated fatty acid oxidation and lysine degradation, NADPH also plays a role in various other mitochondrial processes. We found decreased oxygen consumption and increased extracellular acidification in patient fibroblasts, which may explain why the disease course is consistent with clinical criteria for a mitochondrial disorder. We conclude that DECR deficiency with hyperlysinemia is caused by mitochondrial NADP(H) deficiency due to a mutation in NADK2.
[Mh] MeSH terms primary: Hyperlysinemias/genetics
Mitochondrial Proteins/genetics
NADP/deficiency
Oxidoreductases Acting on CH-CH Group Donors/deficiency
Phosphotransferases (Alcohol Group Acceptor)/genetics
[Mh] MeSH terms secundary: Fibroblasts/metabolism
Humans
Hyperlysinemias/physiopathology
Mutation
Sequence Analysis, DNA
Stress, Physiological
[Pt] Publication type:CASE REPORTS; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Mitochondrial Proteins); 53-59-8 (NADP); EC 1.3.- (Oxidoreductases Acting on CH-CH Group Donors); EC 1.3.1.34 (2,4-dienoyl-CoA reductase); EC 2.7.1.- (NADK2 protein, human); EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
[Em] Entry month:1504
[Cu] Class update date: 140822
[Lr] Last revision date:140822
[Js] Journal subset:IM
[Da] Date of entry for processing:140522
[St] Status:MEDLINE
[do] DOI:10.1093/hmg/ddu218

  4 / 12 MEDLINE  
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[PMID]: 23890588
[Au] Autor:Tondo M; Calpena E; Arriola G; Sanz P; Martorell L; Ormazabal A; Castejon E; Palacin M; Ugarte M; Espinos C; Perez B; Perez-Dueñas B; Pérez-Cerda C; Artuch R
[Ad] Address:Inborn Errors of Metabolism Unit, Hospital Sant Joan de Déu, Barcelona, Spain. Electronic address: mtondo@hsjdbcn.org.
[Ti] Title:Clinical, biochemical, molecular and therapeutic aspects of 2 new cases of 2-aminoadipic semialdehyde synthase deficiency.
[So] Source:Mol Genet Metab;110(3):231-6, 2013 Nov.
[Is] ISSN:1096-7206
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Our aim was to report two new cases of hyperlysinemia type I describing the clinical, biochemical and molecular features of the disease and the outcome of lysine restriction. Two children presented with febrile seizures followed by developmental delay, clumsiness and epilepsy. At age 2 and 8 years a biochemical and genetic diagnosis of hyperlysinemia type I was confirmed and lysine-restricted diet was started in both cases. Three years after initiation of lysine restriction, case 1 had not suffered further seizures. In case 2, tremor and dysmetria improved, but fine motor clumsiness persisted. Mild cognitive impairment was present in both patients despite dietary treatment. Laboratory studies: Plasma, urine and cerebrospinal fluid amino acid concentrations were measured by ion exchange chromatography. Mutation analysis of the AASS gene was performed by directly sequencing the PCR products. The plasma lysine values were higher than 1200 µmol/L in both cases. Additionally, an increase in dibasic aminoaciduria was observed. Lysine restriction decreased plasma lysine values and nearly normalised dibasic aminoaciduria. Mutational screening of the AASS gene revealed that case 1 was a compound heterozygote for c.2662 + 1_2662 + 5delGTAAGinsTT and c.874A>G and that case 2 was a compound heterozygote for c.976_977delCA and c.1925C>G. In conclusion, we present two children with hyperlysinemia type I and neurological impairment in which implementation of lysine-restricted diet achieved a mild improvement of symptoms but did not reverse cognitive impairment. The partial decrease of lysine concentrations and the normalisation of urine excretion of dibasic amino acids after lysine restriction further reinforce the possibility of this therapeutic intervention, although further investigations seem necessary.
[Mh] MeSH terms primary: Hyperlysinemias/diet therapy
Hyperlysinemias/diagnosis
[Mh] MeSH terms secundary: Amino Acid Substitution
Amino Acids/blood
Amino Acids/urine
Child
Child, Preschool
Exons
Female
Gene Order
Genotype
Humans
Hyperlysinemias/genetics
Hyperlysinemias/metabolism
Mutation
Saccharopine Dehydrogenases/genetics
[Pt] Publication type:CASE REPORTS; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Amino Acids); EC 1.5.1.- (AASS protein, human); EC 1.5.1.- (Saccharopine Dehydrogenases)
[Em] Entry month:1405
[Cu] Class update date: 131016
[Lr] Last revision date:131016
[Js] Journal subset:IM
[Da] Date of entry for processing:130730
[St] Status:MEDLINE

  5 / 12 MEDLINE  
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PubMed Central Full text
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[PMID]: 23570448
[Au] Autor:Houten SM; Te Brinke H; Denis S; Ruiter JP; Knegt AC; de Klerk JB; Augoustides-Savvopoulou P; Häberle J; Baumgartner MR; Coskun T; Zschocke J; Sass JO; Poll-The BT; Wanders RJ; Duran M
[Ad] Address:Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam, AZ 1105, The Netherlands. s.m.houten@amc.uva.nl
[Ti] Title:Genetic basis of hyperlysinemia.
[So] Source:Orphanet J Rare Dis;8:57, 2013 Apr 09.
[Is] ISSN:1750-1172
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Hyperlysinemia is an autosomal recessive inborn error of L-lysine degradation. To date only one causal mutation in the AASS gene encoding α-aminoadipic semialdehyde synthase has been reported. We aimed to better define the genetic basis of hyperlysinemia. METHODS: We collected the clinical, biochemical and molecular data in a cohort of 8 hyperlysinemia patients with distinct neurological features. RESULTS: We found novel causal mutations in AASS in all affected individuals, including 4 missense mutations, 2 deletions and 1 duplication. In two patients originating from one family, the hyperlysinemia was caused by a contiguous gene deletion syndrome affecting AASS and PTPRZ1. CONCLUSIONS: Hyperlysinemia is caused by mutations in AASS. As hyperlysinemia is generally considered a benign metabolic variant, the more severe neurological disease course in two patients with a contiguous deletion syndrome may be explained by the additional loss of PTPRZ1. Our findings illustrate the importance of detailed biochemical and genetic studies in any hyperlysinemia patient.
[Mh] MeSH terms primary: Hyperlysinemias/genetics
[Mh] MeSH terms secundary: Base Sequence
Blotting, Western
Cell Line
Cohort Studies
Comparative Genomic Hybridization
DNA Primers
DNA, Complementary/genetics
Humans
Hyperlysinemias/blood
Hyperlysinemias/physiopathology
Mutation
Saccharopine Dehydrogenases/genetics
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (DNA Primers); 0 (DNA, Complementary); EC 1.5.1.- (AASS protein, human); EC 1.5.1.- (Saccharopine Dehydrogenases)
[Em] Entry month:1307
[Cu] Class update date: 150427
[Lr] Last revision date:150427
[Js] Journal subset:IM
[Da] Date of entry for processing:130411
[St] Status:MEDLINE
[do] DOI:10.1186/1750-1172-8-57

  6 / 12 MEDLINE  
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[PMID]: 23350806
[Au] Autor:Pérez B; Gutiérrez-Solana LG; Verdú A; Merinero B; Yuste-Checa P; Ruiz-Sala P; Calvo R; Jalan A; Marín LL; Campos O; Ruiz MÁ; San Miguel M; Vázquez M; Castro M; Ferrer I; Navarrete R; Desviat LR; Lapunzina P; Ugarte M; Pérez-Cerdá C
[Ad] Address:Center of Diagnosis of Molecular Diseases, Center of Molecular Biology UAM-CSIC, Center for Biomedical Network Research on Rare Diseases, Institute for Health Research, IDIPAZ, Autonomous University of Madrid, Madrid, Spain. bperez@cbm.uam.es
[Ti] Title:Clinical, biochemical, and molecular studies in pyridoxine-dependent epilepsy. Antisense therapy as possible new therapeutic option.
[So] Source:Epilepsia;54(2):239-48, 2013 Feb.
[Is] ISSN:1528-1167
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:PURPOSE: Pyridoxine-dependent epilepsy seizure (PDE; OMIM 266100) is a disorder associated with severe seizures that can be controlled pharmacologically with pyridoxine. In the majority of patients with PDE, the disorder is caused by the deficient activity of the enzyme α-aminoadipic semialdehyde dehydrogenase (antiquitin protein), which is encoded by the ALDH7A1 gene. The aim of this work was the clinical, biochemical, and genetic analysis of 12 unrelated patients, mostly from Spain, in an attempt to provide further valuable data regarding the wide clinical, biochemical, and genetic spectrum of the disease. METHODS: The disease was confirmed based on the presence of α-aminoadipic semialdehyde (α-AASA) in urine measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) and pipecolic acid (PA) in plasma and/or cerebrospinal fluid (CSF) measured by high performance liquid chromatography (HPLC)/MS/MS and by sequencing analysis of messenger RNA (mRNA) and genomic DNA of ALDH7A1. KEY FINDINGS: Most of the patients had seizures in the neonatal period, but they responded to vitamin B6 administration. Three patients developed late-onset seizures, and most patients showed mild-to-moderate postnatal developmental delay. All patients had elevated PA and α-AASA levels, even those who had undergone pyridoxine treatment for several years. The clinical spectrum of our patients is not limited to seizures but many of them show associated neurologic dysfunctions such as muscle tone alterations, irritability, and psychomotor retardation. The mutational spectrum of the present patients included 12 mutations, five already reported (c.500A>G, c.919C>T, c.1429G>C c.1217_1218delAT, and c.1482-1G>T) and seven novel sequence changes (c.75C>T, c.319G>T, c.554_555delAA, c.757C>T, c.787 + 1G>T, c.1474T>C, c.1093-?_1620+?). Only one mutation, p.G477R (c.1429G>C), was recurrent; this was detected in four different alleles. Transcriptional profile analysis of one patient's lymphoblasts and ex vivo splicing analysis showed the silent nucleotide change c.75C>T to be a novel splicing mutation creating a new donor splice site inside exon 1. Antisense therapy of the aberrant mRNA splicing in a lymphoblast cell line harboring mutation c.75C>T was successful. SIGNIFICANCE: The present results broaden our knowledge of PDE, provide information regarding the genetic background of PDE in Spain, afford data of use when making molecular-based prenatal diagnosis, and provide a cellular proof-of concept for antisense therapy application.
[Mh] MeSH terms primary: Epilepsy/drug therapy
Epilepsy/genetics
Genetic Therapy/methods
Oligonucleotides, Antisense/therapeutic use
Vitamin B 6 Deficiency/complications
[Mh] MeSH terms secundary: Aldehyde Dehydrogenase/genetics
Cell Line
DNA Mutational Analysis
Epilepsy/etiology
Exons/genetics
Female
Humans
Hyperlysinemias/urine
Infant
Infant, Newborn
Lymphocytes/drug effects
Male
Mutation/genetics
Polymorphism, Single Nucleotide
RNA Splicing
Saccharopine Dehydrogenases/deficiency
Saccharopine Dehydrogenases/urine
Tandem Mass Spectrometry
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Oligonucleotides, Antisense); EC 1.2.1.3 (ALDH7A1 protein, human); EC 1.2.1.3 (Aldehyde Dehydrogenase); EC 1.5.1.- (Saccharopine Dehydrogenases)
[Em] Entry month:1304
[Cu] Class update date: 130206
[Lr] Last revision date:130206
[Js] Journal subset:IM
[Da] Date of entry for processing:130129
[St] Status:MEDLINE
[do] DOI:10.1111/epi.12083

  7 / 12 MEDLINE  
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Wajner, Moacir
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[PMID]: 19370404
[Au] Autor:Tonin AM; Ferreira GC; Schuck PF; Viegas CM; Zanatta A; Leipnitz G; Seminotti B; Duvall Wannmacher CM; Wajner M
[Ad] Address:Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Rua Ramiro Barcelos, RS, Brasil.
[Ti] Title:Inhibition of creatine kinase activity by lysine in rat cerebral cortex.
[So] Source:Metab Brain Dis;24(2):349-60, 2009 Jun.
[Is] ISSN:1573-7365
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Accumulation of lysine (Lys) in tissues and biochemical fluids is the biochemical hallmark of patients affected by familial hyperlysinemia (FH) and also by other inherited neurometabolic disorders. In the present study, we investigated the in vitro effect of Lys on various parameters of energy metabolism in cerebral cortex of 30-day-old Wistar rats. We verified that total (tCK) and cytosolic creatine kinase activities were significantly inhibited by Lys, in contrast to the mitochondrial isoform which was not affected by this amino acid. Furthermore, the inhibitory effect of Lys on tCK activity was totally prevented by reduced glutathione, suggesting a possible role of reactive species oxidizing critical thiol groups of the enzyme. In contrast, Lys did not affect (14)CO(2) production from [U-(14)C] glucose (aerobic glycolytic pathway) and [1-(14)C] acetic acid (citric acid cycle activity) neither the various activities of the electron transfer chain and synaptic Na(+)K(+)-ATPase at concentrations as high as 5.0 mM. Considering the importance of creatine kinase (CK) activity for brain energy metabolism homeostasis and especially ATP transfer and buffering, our results suggest that inhibition of this enzyme by Lys may contribute to the neurological signs presented by symptomatic patients affected by FH and other neurodegenerative disorders in which Lys accumulates.
[Mh] MeSH terms primary: Cerebral Cortex/enzymology
Creatine Kinase/metabolism
Energy Metabolism/physiology
Hyperlysinemias/enzymology
Lysine/metabolism
[Mh] MeSH terms secundary: Analysis of Variance
Animals
Disease Models, Animal
Electron Transport/physiology
Glutathione/physiology
Isoenzymes
Rats
Rats, Wistar
Sodium-Potassium-Exchanging ATPase/metabolism
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Isoenzymes); EC 2.7.3.2 (Creatine Kinase); EC 3.6.3.9 (Sodium-Potassium-Exchanging ATPase); GAN16C9B8O (Glutathione); K3Z4F929H6 (Lysine)
[Em] Entry month:0909
[Cu] Class update date: 171030
[Lr] Last revision date:171030
[Js] Journal subset:IM
[Da] Date of entry for processing:090417
[St] Status:MEDLINE
[do] DOI:10.1007/s11011-009-9131-z

  8 / 12 MEDLINE  
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[PMID]: 17088338
[Au] Autor:Bok LA; Struys E; Willemsen MA; Been JV; Jakobs C
[Ad] Address:Department of Paediatrics, Máxima Medical Center, Veldhoven, The Netherlands. L.Bok@mmc.nl
[Ti] Title:Pyridoxine-dependent seizures in Dutch patients: diagnosis by elevated urinary alpha-aminoadipic semialdehyde levels.
[So] Source:Arch Dis Child;92(8):687-9, 2007 Aug.
[Is] ISSN:1468-2044
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Pyridoxine-dependent seizures (PDS) is a rare, autosomal recessively inherited disorder. Recently alpha-aminoadipic semialdehyde (alpha-AASA) dehydrogenase deficiency was identified as a major cause of PDS, which causes accumulation of both alpha-AASA and pipecolic acid (PA) in body fluids. METHODS: We studied urinary and plasma alpha-AASA and PA levels in 12 Dutch clinically diagnosed patients with PDS. RESULTS: Alpha-AASA was elevated in both urine and plasma in 10 patients. In these patients plasma PA levels were also elevated but urinary PA levels were normal. DISCUSSION: In all patients with clinically definite PDS, and in most patients with probable or possible PDS, the clinical diagnosis of PDS could be confirmed at the metabolite level. Non-invasive urinary screening for alpha-AASA accumulation provides a reliable tool to diagnose PDS and can save these patients from the classical and potentially dangerous pyridoxine withdrawal test to prove PDS.
[Mh] MeSH terms primary: Hyperlysinemias/diagnosis
Pipecolic Acids
Seizures/diagnosis
[Mh] MeSH terms secundary: Aldehyde Dehydrogenase/blood
Aldehyde Dehydrogenase/urine
Biomarkers/blood
Biomarkers/urine
Female
Humans
Netherlands
Pipecolic Acids/blood
Pipecolic Acids/urine
Pyridoxine/therapeutic use
Seizures/blood
Seizures/urine
Vitamin B Complex/therapeutic use
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Biomarkers); 0 (Pipecolic Acids); 12001-76-2 (Vitamin B Complex); EC 1.2.1.3 (ALDH7A1 protein, human); EC 1.2.1.3 (Aldehyde Dehydrogenase); KV2JZ1BI6Z (Pyridoxine)
[Em] Entry month:0708
[Cu] Class update date: 151119
[Lr] Last revision date:151119
[Js] Journal subset:AIM; IM
[Da] Date of entry for processing:061108
[St] Status:MEDLINE

  9 / 12 MEDLINE  
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[PMID]: 15759964
[Au] Autor:Tofil NM; Benner KW; Winkler MK
[Ad] Address:Division of Pediatric Critical Care Medicine, Department of Pediatrics, the University of Alabama at Birmingham, Birmingham, AL, USA. ntofil@peds.uab.edu
[Ti] Title:Fatal hypermagnesemia caused by an Epsom salt enema: a case illustration.
[So] Source:South Med J;98(2):253-6, 2005 Feb.
[Is] ISSN:0038-4348
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The authors describe a case of fatal hypermagnesemia caused by an Epsom salt enema. A 7-year-old male presented with cardiac arrest and was found to have a serum magnesium level of 41.2 mg/dL (33.9 mEq/L) after having received an Epsom salt enema earlier that day. The medical history of Epsom salt, the common causes and symptoms of hypermagnesemia, and the treatment of hypermagnesemia are reviewed. The easy availability of magnesium, the subtle initial symptoms of hypermagnesemia, and the need for education about the toxicity of magnesium should be of interest to physicians.
[Mh] MeSH terms primary: Hyperlysinemias/etiology
Magnesium Sulfate/adverse effects
[Mh] MeSH terms secundary: Abdominal Pain/therapy
Child
Enema/adverse effects
Fatal Outcome
Heart Arrest/therapy
Humans
Magnesium/blood
Magnesium Sulfate/therapeutic use
Male
[Pt] Publication type:CASE REPORTS; JOURNAL ARTICLE
[Nm] Name of substance:7487-88-9 (Magnesium Sulfate); I38ZP9992A (Magnesium)
[Em] Entry month:0505
[Cu] Class update date: 131121
[Lr] Last revision date:131121
[Js] Journal subset:AIM; IM
[Da] Date of entry for processing:050312
[St] Status:MEDLINE

  10 / 12 MEDLINE  
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[PMID]: 10775527
[Au] Autor:Sacksteder KA; Biery BJ; Morrell JC; Goodman BK; Geisbrecht BV; Cox RP; Gould SJ; Geraghty MT
[Ad] Address:Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
[Ti] Title:Identification of the alpha-aminoadipic semialdehyde synthase gene, which is defective in familial hyperlysinemia.
[So] Source:Am J Hum Genet;66(6):1736-43, 2000 Jun.
[Is] ISSN:0002-9297
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The first two steps in the mammalian lysine-degradation pathway are catalyzed by lysine-ketoglutarate reductase and saccharopine dehydrogenase, respectively, resulting in the conversion of lysine to alpha-aminoadipic semialdehyde. Defects in one or both of these activities result in familial hyperlysinemia, an autosomal recessive condition characterized by hyperlysinemia, lysinuria, and variable saccharopinuria. In yeast, lysine-ketoglutarate reductase and saccharopine dehydrogenase are encoded by the LYS1 and LYS9 genes, respectively, and we searched the available sequence databases for their human homologues. We identified a single cDNA that encoded an apparently bifunctional protein, with the N-terminal half similar to that of yeast LYS1 and with the C-terminal half similar to that of yeast LYS9. This bifunctional protein has previously been referred to as "alpha-aminoadipic semialdehyde synthase," and we have tentatively designated this gene "AASS." The AASS cDNA contains an open reading frame of 2,781 bp predicted to encode a 927-amino-acid-long protein. The gene has been sequenced and contains 24 exons scattered over 68 kb and maps to chromosome 7q31.3. Northern blot analysis revealed the presence of several transcripts in all tissues examined, with the highest expression occurring in the liver. We sequenced the genomic DNA from a single patient with hyperlysinemia (JJa). The patient is the product of a consanguineous mating and is homozygous for an out-of-frame 9-bp deletion in exon 15, which results in a premature stop codon at position 534 of the protein. On the basis of these and other results, we propose that AASS catalyzes the first two steps of the major lysine-degradation pathway in human cells and that inactivating mutations in the AASS gene are a cause of hyperlysinemia.
[Mh] MeSH terms primary: Hyperlysinemias/enzymology
Hyperlysinemias/genetics
Multienzyme Complexes/genetics
Mutation/genetics
Saccharopine Dehydrogenases/genetics
[Mh] MeSH terms secundary: Amino Acid Sequence
Base Sequence
Chromosomes, Human, Pair 7/genetics
Cloning, Molecular
Consanguinity
DNA Mutational Analysis
Exons/genetics
Female
Gene Expression Profiling
Genes, Recessive/genetics
Homozygote
Humans
In Situ Hybridization, Fluorescence
Lysine/metabolism
Male
Molecular Sequence Data
Multienzyme Complexes/chemistry
Multienzyme Complexes/metabolism
Physical Chromosome Mapping
RNA Splice Sites/genetics
RNA, Messenger/analysis
RNA, Messenger/genetics
Saccharopine Dehydrogenases/chemistry
Saccharopine Dehydrogenases/metabolism
Sequence Alignment
Sequence Deletion/genetics
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
[Nm] Name of substance:0 (Multienzyme Complexes); 0 (RNA Splice Sites); 0 (RNA, Messenger); EC 1.5.1.- (AASS protein, human); EC 1.5.1.- (Saccharopine Dehydrogenases); K3Z4F929H6 (Lysine)
[Em] Entry month:0106
[Cu] Class update date: 161019
[Lr] Last revision date:161019
[Js] Journal subset:IM
[Da] Date of entry for processing:000425
[St] Status:MEDLINE


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