Newborn Screening for Tyrosinemia Type I: Further Evidence that Succinylacetone Determination on Blood Spot Is Essential

Abstract

Tyrosinemia type I is a genetic disorder characterized by accumulation in the blood and urine of the toxic metabolite succinylacetone (SUAC), not detectable in healthy samples. In many countries, newborns are screened for tyrosinemia type I using tyrosine as a primary marker. Unfortunately, tyrosine accumulation may take longer to occur and it may be not obvious when specimens are collected, in the first few days of life, as for newborn screening. In 2008, we reported changes to simultaneously measure acylcarnitines, amino acids, and SUAC during expanded newborn screening. We established the usefulness of this method after identifying a first asymptomatic newborn affected by tyrosinemia type I. Now we report a second infant with positive SUAC screening result (14.1 mmol/L, n.v.<2) and normal tyrosine concentration (74 mmol/L; n.v.<250). We also performed molecular analysis of FAH gene in both patients after diagnosis at newborn screening. They had consanguineous parents and were both homozygous for two known disease-causing mutations of the FAH gene. The outcome of patients detected in the MS/MS screening is significantly favorable. We also report our results of newborn screening for tyrosinemia type I before and after inclusion of SUAC as a primary marker for this disease.

Expanded newborn screening by mass spectrometry: New tests, future perspectives

“…Using this strategy, several two‐tier tests have been developed such as succinylacetone (SUAC), a specific marker for Tyrosinemia I (OMIM 276700), recently included in the NBS panel (la Marca et al, ; Turgeon et al, ). Although, in our experience, false positive rates for SUAC are very low (la Marca et al, ), a sample contamination cannot be excluded. A newborn falsely suspected for Tyr I causes a high cost of hospitalization, without considering the parental stress involved.…”

Newborn screening for Tyrosinemia type 1 using succinylacetone – a systematic review of test accuracy

“…The remainder of the studies had an unclear risk of bias as they did not report the method of diagnosis, or did not report sufficient information to allow a judgement to be made [12, 14, 17–22]. Applicability concerns were high in seven studies as babies that screened negative in studies reporting screening experiences or were used as controls did not receive an appropriate reference standard, i.e.…”

“…For the case–control studies, sensitivity was estimated to be 100% in each of the five studies, which included 29 cases in total [14, 17, 21, 23, 24]. Specificity was estimated to be 100% in four studies [14, 22–24].…”

A Rapid Screening Test on Dried Blood for the Neonatal Diagnosis of Tyrosinemia Type I

“…The presence of succinyl acetone in urine or blood is the characteristic test for the diagnosis of tyrosinemia type I which if untreated and without liver transplantation, will be usually fatal before the age 10 years ( 7 ). Affected children may present with liver or kidney failure, neurological crisis, rickets, failure to thrive, and hepatocellular carcinoma ( 8 ).…”