False-positive newborn screening mimicking glutaric aciduria type I in infants with renal insufficiency.
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.
Hennermann
Julia B
JB
Department of Pediatrics, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. julia.hennermann@charite.de
Roloff
Sylvia
S
Gellermann
Jutta
J
Grüters
Annette
A
Klein
Jeannette
J
D000592:Amino Acid Metabolism, Inborn Errors / Q000097:blood / Q000175:diagnosis*; D001928:Brain Diseases, Metabolic / Q000097:blood / Q000175:diagnosis*; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D003937:Diagnosis, Differential; D005189:False Positive Reactions; D005260:Female; D005858:Germany; D050770:Glutaryl-CoA Dehydrogenase / Q000097:blood / Q000172:deficiency; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening; D051437:Renal Insufficiency / Q000097:blood / Q000151:congenital / Q000175:diagnosis*
C053168:glutarylcarnitine; D050770:Glutaryl-CoA Dehydrogenase; D002331:Carnitine