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.
Mol Genet Metab
; 142(2): 108489, 2024 Jun.
Article
in En
| MEDLINE
| ID: mdl-38718669
ABSTRACT
BACKGROUND:
Canavan 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.METHODS:
We 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.RESULTS:
Measuring 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).CONCLUSIONS:
We 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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Neonatal Screening
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Aspartic Acid
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Canavan Disease
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Tandem Mass Spectrometry
/
Dried Blood Spot Testing
Limits:
Child, preschool
/
Female
/
Humans
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Infant
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Male
/
Newborn
Language:
En
Journal:
Mol Genet Metab
Journal subject:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
METABOLISMO
Year:
2024
Type:
Article