Maleic acid is a biomarker for maleylacetoacetate isomerase deficiency: implications for newborn screening of tyrosinemia type 1

K. van Vliet, A. M. Dijkstra, M. J. Bouva, J. van der Krogt, K. Bijsterveld, F. van der Sluijs, M. G. de Sain-van der Velden, K. Koop, A. Rossi, J. A. Thomas, C. A. Patera, M. B.G. Kiewiet, P. J. Waters, D. Cyr, A. Boelen, F. J. van Spronsen, M. R. Heiner-Fokkema*

*Corresponding author voor dit werk

OnderzoeksoutputAcademicpeer review

1 Citaat (Scopus)
42 Downloads (Pure)

Samenvatting

Dried blood spot succinylacetone (SA) is often used as a biomarker for newborn screening (NBS) for tyrosinemia type 1 (TT1). However, false-positive SA results are often observed. Elevated SA may also be due to maleylacetoacetate isomerase deficiency (MAAI-D), which appears to be clinically insignificant. This study investigated whether urine organic acid (uOA) and quantitative urine maleic acid (Q-uMA) analyses can distinguish between TT1 and MAAI-D. We reevaluated/measured uOA (GC–MS) and/or Q-uMA (LC–MS/MS) in available urine samples of nine referred newborns (2 TT1, 7 false-positive), eight genetically confirmed MAAI-D children, and 66 controls. Maleic acid was elevated in uOA of 5/7 false-positive newborns and in the three available samples of confirmed MAAI-D children, but not in TT1 patients. Q-uMA ranged from not detectable to 1.16 mmol/mol creatinine in controls (n = 66) and from 0.95 to 192.06 mmol/mol creatinine in false-positive newborns and MAAI-D children (n = 10). MAAI-D was genetically confirmed in 4/7 false-positive newborns, all with elevated Q-uMA, and rejected in the two newborns with normal Q-uMA. No sample was available for genetic analysis of the last false-positive infant with elevated Q-uMA. Our study shows that MAAI-D is a recognizable cause of false-positive TT1 NBS results. Elevated urine maleic acid excretion seems highly effective in discriminating MAAI-D from TT1.

Originele taal-2English
Pagina's (van-tot)1104-1113
Aantal pagina's10
TijdschriftJournal of Inherited Metabolic Disease
Volume46
Nummer van het tijdschrift6
DOI's
StatusPublished - nov.-2023

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