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

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. [ABSTRACT FROM AUTHOR]

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