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Open AccessCase Report

The Importance of Succinylacetone: Tyrosinemia Type I Presenting with Hyperinsulinism and Multiorgan Failure Following Normal Newborn Screening

1
Department of Pediatrics, Division of Human Genetics, Section of Biochemical Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
2
Department of Pediatrics, Pediatric Residency Program, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
3
Department of Pediatrics, Division of Neonatology, Children’s Hospital of Philadelphia, PA 19104, USA
4
Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Neonatal Screen. 2020, 6(2), 39; https://doi.org/10.3390/ijns6020039
Received: 7 April 2020 / Revised: 11 May 2020 / Accepted: 14 May 2020 / Published: 16 May 2020
Tyrosinemia type 1 (TT1) is an inborn error of tyrosine metabolism with features including liver dysfunction, cirrhosis, and hepatocellular carcinoma; renal dysfunction that may lead to failure to thrive and bone disease; and porphyric crises. Once fatal in most infantile-onset cases, pre-symptomatic diagnosis through newborn screening (NBS) protocols, dietary management, and pharmacotherapy with nitisinone have improved outcomes. Succinylacetone provides a sensitive and specific marker for the detection of TT1 but is not universally utilized in screening protocols for the disease. Here, we report an infant transferred to our facility for evaluation and management of hyperinsulinism who subsequently developed acute-onset liver, respiratory, and renal failure around one month of life. She was found to have TT1 caused by novel pathogenic variant in fumarylacetoacetate hydrolase (c.1014 delC, p.Cys 338 Ter). Her NBS, which utilized tyrosine as a primary marker, had been reported as normal, with a tyrosine level of 151 µmol/L (reference: < 280 µmol/L). Retrospective analysis of dried blood spot samples via tandem mass spectrometry showed detectable succinylacetone ranging 4.65–10.34 µmol/L. To our knowledge, this is the first patient with TT1 whose initial presenting symptom was hyperinsulinemic hypoglycemia. The case highlights the importance of maintaining a high suspicion for metabolic disease in critically ill children, despite normal NBS. We also use the case to advocate for NBS for TT1 using succinylacetone quantitation. View Full-Text
Keywords: tyrosinemia type I; hereditary tyrosinemia; newborn screening; succinylacetone; Tyrosine tyrosinemia type I; hereditary tyrosinemia; newborn screening; succinylacetone; Tyrosine
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Priestley, J.R.C.; Alharbi, H.; Callahan, K.P.; Guzman, H.; Payan-Walters, I.; Smith, L.; Ficicioglu, C.; Ganetzky, R.D.; Ahrens-Nicklas, R.C. The Importance of Succinylacetone: Tyrosinemia Type I Presenting with Hyperinsulinism and Multiorgan Failure Following Normal Newborn Screening. Int. J. Neonatal Screen. 2020, 6, 39.

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