False-positive newborn screening mimicking glutaric aciduria type I in infants with renal insufficiency.

Publisher: Wiley Country of Publication: United States NLM ID: 7910918 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-2665 (Electronic) Linking ISSN: 01418955 NLM ISO Abbreviation: J Inherit Metab Dis Subsets: MEDLINE

Publication: 2019- : [Hoboken, NJ] : Wiley
Original Publication: [Lancaster, Eng.] MTP Press.

Neonatal Screening*; Amino Acid Metabolism, Inborn Errors/*diagnosis ; Brain Diseases, Metabolic/*diagnosis ; Renal Insufficiency/*diagnosis; Amino Acid Metabolism, Inborn Errors/blood ; Brain Diseases, Metabolic/blood ; Carnitine/analogs & derivatives ; Carnitine/blood ; Diagnosis, Differential ; False Positive Reactions ; Female ; Germany ; Glutaryl-CoA Dehydrogenase/blood ; Glutaryl-CoA Dehydrogenase/deficiency ; Humans ; Infant, Newborn ; Male ; Renal Insufficiency/blood ; Renal Insufficiency/congenital

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.

Pediatr Res. 2007 Sep;62(3):357-63. (PMID: 17622945)
Clin Chem. 2001 Nov;47(11):1945-55. (PMID: 11673361)
J Inherit Metab Dis. 2008 Apr;31(2):188-93. (PMID: 18404412)
Pediatrics. 2001 May;107(5):1184-7. (PMID: 11331707)
Cancer Biol Ther. 2005 Aug;4(8):815-8. (PMID: 16210916)
J Inherit Metab Dis. 2007 Feb;30(1):5-22. (PMID: 17203377)
J Inherit Metab Dis. 1995;18(3):358-9. (PMID: 7474906)
J Inherit Metab Dis. 2004;27(6):851-9. (PMID: 15505392)
J Inherit Metab Dis. 2004;27(4):465-71. (PMID: 15303003)
Ann Pharmacother. 2005 Jan;39(1):157-61. (PMID: 15590878)
Eur J Pediatr. 2008 May;167(5):569-73. (PMID: 17661081)
J Neurochem. 2006 Apr;97(1):162-73. (PMID: 16524379)
Birth Defects Res A Clin Mol Teratol. 2005 Feb;73(2):123-30. (PMID: 15669052)
N Engl J Med. 2003 Jun 5;348(23):2304-12. (PMID: 12788994)
Mol Genet Metab. 2005 Nov;86(3):417-20. (PMID: 16183314)
J Inherit Metab Dis. 2006 Apr-Jun;29(2-3):378-82. (PMID: 16763905)

109006-11-3 (glutarylcarnitine)
EC 1.3.8.6 (Glutaryl-CoA Dehydrogenase)
S7UI8SM58A (Carnitine)

Glutaric Acidemia I

Date Created: 20091225 Date Completed: 20130805 Latest Revision: 20211020

20221213

10.1007/s10545-009-9017-6

20033292