Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

A newborn screening approach to diagnose 3-hydroxy-3-methylglutaryl-CoA lyase deficiency

J. Václavík, L. Mádrová, Š. Kouřil, J. de Sousa, R. Brumarová, H. Janečková, J. Jáčová, D. Friedecký, M. Knapková, LAJ. Kluijtmans, SC. Grünert, FM. Vaz, N. Janzen, RJA. Wanders, RA. Wevers, T. Adam,

. 2020 ; 54 (1) : 79-86. [pub] 20200414

Language English Country United States

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc20022123

3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD) is a rare autosomal recessively inherited metabolic disorder. Patients suffer from avoidable neurologically devastating metabolic decompensations and thus would benefit from newborn screening (NBS). The diagnosis is currently made by measuring dry blood spot acylcarnitines (C5OH and C6DC) followed by urinary organic acid profiling for the differential diagnosis from several other disorders. Using untargeted metabolomics (reversed-phase UHPLC coupled to an Orbitrap Elite hybrid mass spectrometer) of plasma samples from 5 HMGCLD patients and 19 age-matched controls, we found 3-methylglutaconic acid and 3-hydroxy-3-methylglutaric acid, together with 3-hydroxyisovalerylcarnitine as the most discriminating metabolites between the groups. In order to evaluate the NBS potential of these metabolites we quantified the most discriminating metabolites from untargeted metabolomics in 23 blood spots from 4 HMGCLD patients and 55 controls by UHPLC tandem mass spectrometry. The results provide a tool for expanded NBS of HMGCLD using tandem mass spectrometry. Selected reaction monitoring transition 262/85 could be used in a first-tier NBS analysis to screen for elevated 3-hydroxyisovalerylcarnitine. In a positive case, a second-tier analysis of 3-hydroxy-3-methylglutaric acid and 3-methylglutaconic acid in a dry blood spot using UHPLC tandem mass spectrometry instruments confirms the diagnosis. In conclusion, we describe the identification of new diagnostic biomarkers for HMGCLD and their application in NBS in dry blood spots. By using second-tier testing, all patients with HMGCLD were unequivocally and correctly diagnosed.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc20022123
003      
CZ-PrNML
005      
20240125121441.0
007      
ta
008      
201125s2020 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1002/jmd2.12118 $2 doi
035    __
$a (PubMed)32685354
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Václavík, Jan $u Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University Olomouc Olomouc Czech Republic. Laboratory of Inherited Metabolic Disorders, Department of Clinical Chemistry University Hospital in Olomouc Olomouc Czech Republic.
245    12
$a A newborn screening approach to diagnose 3-hydroxy-3-methylglutaryl-CoA lyase deficiency / $c J. Václavík, L. Mádrová, Š. Kouřil, J. de Sousa, R. Brumarová, H. Janečková, J. Jáčová, D. Friedecký, M. Knapková, LAJ. Kluijtmans, SC. Grünert, FM. Vaz, N. Janzen, RJA. Wanders, RA. Wevers, T. Adam,
520    9_
$a 3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD) is a rare autosomal recessively inherited metabolic disorder. Patients suffer from avoidable neurologically devastating metabolic decompensations and thus would benefit from newborn screening (NBS). The diagnosis is currently made by measuring dry blood spot acylcarnitines (C5OH and C6DC) followed by urinary organic acid profiling for the differential diagnosis from several other disorders. Using untargeted metabolomics (reversed-phase UHPLC coupled to an Orbitrap Elite hybrid mass spectrometer) of plasma samples from 5 HMGCLD patients and 19 age-matched controls, we found 3-methylglutaconic acid and 3-hydroxy-3-methylglutaric acid, together with 3-hydroxyisovalerylcarnitine as the most discriminating metabolites between the groups. In order to evaluate the NBS potential of these metabolites we quantified the most discriminating metabolites from untargeted metabolomics in 23 blood spots from 4 HMGCLD patients and 55 controls by UHPLC tandem mass spectrometry. The results provide a tool for expanded NBS of HMGCLD using tandem mass spectrometry. Selected reaction monitoring transition 262/85 could be used in a first-tier NBS analysis to screen for elevated 3-hydroxyisovalerylcarnitine. In a positive case, a second-tier analysis of 3-hydroxy-3-methylglutaric acid and 3-methylglutaconic acid in a dry blood spot using UHPLC tandem mass spectrometry instruments confirms the diagnosis. In conclusion, we describe the identification of new diagnostic biomarkers for HMGCLD and their application in NBS in dry blood spots. By using second-tier testing, all patients with HMGCLD were unequivocally and correctly diagnosed.
655    _2
$a časopisecké články $7 D016428
700    1_
$a Mádrová, Lucie $u Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University Olomouc Olomouc Czech Republic. Laboratory of Inherited Metabolic Disorders, Department of Clinical Chemistry University Hospital in Olomouc Olomouc Czech Republic.
700    1_
$a Kouřil, Štěpán $u Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University Olomouc Olomouc Czech Republic. Laboratory of Inherited Metabolic Disorders, Department of Clinical Chemistry University Hospital in Olomouc Olomouc Czech Republic. $7 xx0313061
700    1_
$a de Sousa, Julie $u Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University Olomouc Olomouc Czech Republic. Laboratory of Inherited Metabolic Disorders, Department of Clinical Chemistry University Hospital in Olomouc Olomouc Czech Republic. Department of Mathematical Analysis and Applications of Mathematics, Faculty of Science Palacký University Olomouc Olomouc Czech Republic.
700    1_
$a Brumarová, Radana $u Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University Olomouc Olomouc Czech Republic. Laboratory of Inherited Metabolic Disorders, Department of Clinical Chemistry University Hospital in Olomouc Olomouc Czech Republic.
700    1_
$a Janečková, Hana $u Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University Olomouc Olomouc Czech Republic. Laboratory of Inherited Metabolic Disorders, Department of Clinical Chemistry University Hospital in Olomouc Olomouc Czech Republic.
700    1_
$a Jáčová, Jaroslava $u Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University Olomouc Olomouc Czech Republic. Laboratory of Inherited Metabolic Disorders, Department of Clinical Chemistry University Hospital in Olomouc Olomouc Czech Republic.
700    1_
$a Friedecký, David $u Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University Olomouc Olomouc Czech Republic. Laboratory of Inherited Metabolic Disorders, Department of Clinical Chemistry University Hospital in Olomouc Olomouc Czech Republic.
700    1_
$a Knapková, Mária $u Banská Bystrica Children's University Hospital Banská Bystrica Slovakia.
700    1_
$a Kluijtmans, Leo A J $u Translational Metabolic Laboratory, Department of Laboratory Medicine Radboud University Medical Centre GA Nijmegen Netherlands.
700    1_
$a Grünert, Sarah C $u Department of General Pediatrics, Adolescent Medicine and Neonatology Medical Center - University of Freiburg, Faculty of Medicine Freiburg Germany.
700    1_
$a Vaz, Frédéric M $u Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry Amsterdam Netherlands.
700    1_
$a Janzen, Nils $u Screening-Labor Hannover Hannover Germany. Department of Clinical Chemistry Hannover Medical School Hannover Germany.
700    1_
$a Wanders, Ronald J A $u Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry Amsterdam Netherlands.
700    1_
$a Wevers, Ron A $u Translational Metabolic Laboratory, Department of Laboratory Medicine Radboud University Medical Centre GA Nijmegen Netherlands.
700    1_
$a Adam, Tomáš $u Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University Olomouc Olomouc Czech Republic. Laboratory of Inherited Metabolic Disorders, Department of Clinical Chemistry University Hospital in Olomouc Olomouc Czech Republic.
773    0_
$w MED00181481 $t JIMD reports $x 2192-8304 $g Roč. 54, č. 1 (2020), s. 79-86
856    41
$u https://pubmed.ncbi.nlm.nih.gov/32685354 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20201125 $b ABA008
991    __
$a 20240125121435 $b ABA008
999    __
$a ind $b bmc $g 1591830 $s 1112795
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2020 $b 54 $c 1 $d 79-86 $e 20200414 $i 2192-8304 $m JIMD reports $n JIMD Rep $x MED00181481
LZP    __
$a Pubmed-20201125

Find record

Citation metrics

Archiving options