Abstract
Glutaric aciduria type I (GA I), an autosomal-recessive deficiency of glutaryl-CoA-dehydrogenase, leads to encephalopathic crises resulting in irreversible neurological damage. As early diagnosis and implementation of appropriate treatment has significant benefit for these patients, GA I has been implemented in the extended newborn screening program in several countries. Screening parameter is glutarylcarnitine (C5DC) with its ratios. From 1 January 2005 until 31 December 2008, 173,846 newborns were examined by neonatal screening in our screening center. C5DC and/or at least three C5DC/acylcarnitine ratios were increased in 53 newborns (0.03%) and persisted in 11 infants after recall. GA I was not confirmed in any of these infants, but all 11 infants were suffering from renal insufficiency due to congenital (5/11) or acquired (6/11) renal disease. C5DC was shown to be significantly associated with renal affection and was significantly higher in infants with congenital renal insufficiency than in those with acquired renal insufficiency (p = 0.011). Creatinine correlated significantly with C5DC (p = 0.001) and all C5DC/acylcarnitine ratios, mainly with C5DC/(C8 + C10), C5DC/C0, C5DC/C2, C5DC/C4, and C5DC/C8 (for all: p = 0.001). Glutarylcarnitinemia associated with renal insufficiency has not yet been studied systematically. Renal damage in neonates might lead to disturbances in renal transporter systems of glutaric acid and its metabolites and a decreased excretion of C5DC, thus resulting in an increase of plasma C5DC. Therefore, newborns presenting with a positive screening indicating GA I may be considered not only to suffer from GA I but from renal insufficiency as well.
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Abbreviations
- C0:
-
Free carnitine
- C10-OH:
-
Hydroxydecanoylcarnitine
- C12:
-
Dodecanoylcarnitine
- C16:
-
Palmitoylcarnitine
- C2:
-
Acetylcarnitine
- C4:
-
Butyrylcarnitine
- C5DC:
-
Glutarylcarnitine
- C8:
-
Octanoylcarnitine
- GA I:
-
Glutaric aciduria type I
- GCDH:
-
Glutaryl-CoA dehydrogenase
- MADD:
-
Multiple acyl-CoA dehydrogenase deficiency
- MCADD:
-
Medium-chain acyl-CoA dehydrogenase deficiency
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Communicated by: Georg Hoffmann
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Hennermann, J.B., Roloff, S., Gellermann, J. et al. False-positive newborn screening mimicking glutaric aciduria type I in infants with renal insufficiency. J Inherit Metab Dis 32 (Suppl 1), 355–359 (2009). https://doi.org/10.1007/s10545-009-9017-6
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DOI: https://doi.org/10.1007/s10545-009-9017-6