Quantification of N-acetyl-L-aspartate in dried blood spots: A simple and fast LC-MS/MS neonatal screening method for the diagnosis of Canavan disease
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Quantification of N-acetyl-L-aspartate in dried blood spots: A simple and fast LC-MS/MS neonatal screening method for the diagnosis of Canavan disease. / Posern, Christian; Dreyer, Benjamin; Maier, Sarah Lena; Eichler, Florian; Gelb, Michael H; Santer, Rene; Bley, Annette; Murko, Simona.
In: MOL GENET METAB, Vol. 142, No. 2, 108489, 06.2024, p. 108489.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Quantification of N-acetyl-L-aspartate in dried blood spots: A simple and fast LC-MS/MS neonatal screening method for the diagnosis of Canavan disease
AU - Posern, Christian
AU - Dreyer, Benjamin
AU - Maier, Sarah Lena
AU - Eichler, Florian
AU - Gelb, Michael H
AU - Santer, Rene
AU - Bley, Annette
AU - Murko, Simona
PY - 2024/6
Y1 - 2024/6
N2 - BackgroundCanavan disease is a devastating neurometabolic disorder caused by accumulation of N acetylaspartate in brain and body fluids due to genetic defects in the aspartoacylase gene (ASPA). New gene therapies are on the horizon but will require early presymptomatic diagnosis to be fully effective.MethodsWe therefore developed a fast and highly sensitive liquid chromatography mass spectrometry (LC-MS/MS)-based method for quantification of N-acetylaspartate in dried blood spots and established reference ranges for neonates and older controls. With this test, we investigated 45 samples of 25 Canavan patients including 8 with a neonatal sample.ResultsMeasuring N-acetylaspartate concentration in dried blood with this novel test, all Canavan patients (with variable severity) were well separated from the control group (median; range: 5.7; 1.6–13.6 μmol/L [n = 45] vs 0.44; 0.24–0.99 μmol/L [n = 59] (p < 0.05)). There was also no overlap when comparing neonatal samples of Canavan patients (7.3; 5.1–9.9 μmol/L [n = 8]) and neonatal controls (0.93; 0.4–1.8 μmol/L [n = 784]) (p < 0.05).ConclusionsWe have developed a new LC-MS/MS-based screening test for early postnatal diagnosis of Canavan disease that should be further evaluated in a population-based study once a promising treatment becomes available. The method meets the general requirements of newborn screening and should be appropriate for multiplexing with other screening approaches that combine chromatographic and mass spectrometry techniques.
AB - BackgroundCanavan disease is a devastating neurometabolic disorder caused by accumulation of N acetylaspartate in brain and body fluids due to genetic defects in the aspartoacylase gene (ASPA). New gene therapies are on the horizon but will require early presymptomatic diagnosis to be fully effective.MethodsWe therefore developed a fast and highly sensitive liquid chromatography mass spectrometry (LC-MS/MS)-based method for quantification of N-acetylaspartate in dried blood spots and established reference ranges for neonates and older controls. With this test, we investigated 45 samples of 25 Canavan patients including 8 with a neonatal sample.ResultsMeasuring N-acetylaspartate concentration in dried blood with this novel test, all Canavan patients (with variable severity) were well separated from the control group (median; range: 5.7; 1.6–13.6 μmol/L [n = 45] vs 0.44; 0.24–0.99 μmol/L [n = 59] (p < 0.05)). There was also no overlap when comparing neonatal samples of Canavan patients (7.3; 5.1–9.9 μmol/L [n = 8]) and neonatal controls (0.93; 0.4–1.8 μmol/L [n = 784]) (p < 0.05).ConclusionsWe have developed a new LC-MS/MS-based screening test for early postnatal diagnosis of Canavan disease that should be further evaluated in a population-based study once a promising treatment becomes available. The method meets the general requirements of newborn screening and should be appropriate for multiplexing with other screening approaches that combine chromatographic and mass spectrometry techniques.
U2 - 10.1016/j.ymgme.2024.108489
DO - 10.1016/j.ymgme.2024.108489
M3 - SCORING: Journal article
C2 - 38718669
VL - 142
SP - 108489
JO - MOL GENET METAB
JF - MOL GENET METAB
SN - 1096-7192
IS - 2
M1 - 108489
ER -