The Importance of Succinylacetone: Tyrosinemia Type I Presenting with Hyperinsulinism and Multiorgan Failure Following Normal Newborn Screening
Tyrosinemia type I (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-symptomati...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-05-01
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| Series: | International Journal of Neonatal Screening |
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| Online Access: | https://www.mdpi.com/2409-515X/6/2/39 |
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| author | Jessica R. C. Priestley Hana Alharbi Katharine Press Callahan Herodes Guzman Irma Payan-Walters Ligia Smith Can Ficicioglu Rebecca D. Ganetzky Rebecca C. Ahrens-Nicklas |
| author_facet | Jessica R. C. Priestley Hana Alharbi Katharine Press Callahan Herodes Guzman Irma Payan-Walters Ligia Smith Can Ficicioglu Rebecca D. Ganetzky Rebecca C. Ahrens-Nicklas |
| author_sort | Jessica R. C. Priestley |
| collection | DOAJ |
| description | Tyrosinemia type I (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. |
| first_indexed | 2024-03-10T19:47:17Z |
| format | Article |
| id | doaj.art-08630d920cd6486c840ff141d3a206fb |
| institution | Directory Open Access Journal |
| issn | 2409-515X |
| language | English |
| last_indexed | 2024-03-10T19:47:17Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Neonatal Screening |
| spelling | doaj.art-08630d920cd6486c840ff141d3a206fb2023-11-20T00:42:05ZengMDPI AGInternational Journal of Neonatal Screening2409-515X2020-05-01623910.3390/ijns6020039The Importance of Succinylacetone: Tyrosinemia Type I Presenting with Hyperinsulinism and Multiorgan Failure Following Normal Newborn ScreeningJessica R. C. Priestley0Hana Alharbi1Katharine Press Callahan2Herodes Guzman3Irma Payan-Walters4Ligia Smith5Can Ficicioglu6Rebecca D. Ganetzky7Rebecca C. Ahrens-Nicklas8Department of Pediatrics, Division of Human Genetics, Section of Biochemical Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USADepartment of Pediatrics, Division of Human Genetics, Section of Biochemical Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USADepartment of Pediatrics, Division of Neonatology, Children’s Hospital of Philadelphia, PA 19104, USADepartment of Pediatrics, Pediatric Residency Program, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USADepartment of Pediatrics, Division of Human Genetics, Section of Biochemical Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USADepartment of Pediatrics, Division of Human Genetics, Section of Biochemical Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USADepartment of Pediatrics, Division of Human Genetics, Section of Biochemical Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USADepartment of Pediatrics, Division of Human Genetics, Section of Biochemical Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USADepartment of Pediatrics, Division of Human Genetics, Section of Biochemical Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USATyrosinemia type I (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.https://www.mdpi.com/2409-515X/6/2/39tyrosinemia type Ihereditary tyrosinemianewborn screeningsuccinylacetoneTyrosine |
| spellingShingle | Jessica R. C. Priestley Hana Alharbi Katharine Press Callahan Herodes Guzman Irma Payan-Walters Ligia Smith Can Ficicioglu Rebecca D. Ganetzky Rebecca C. Ahrens-Nicklas The Importance of Succinylacetone: Tyrosinemia Type I Presenting with Hyperinsulinism and Multiorgan Failure Following Normal Newborn Screening International Journal of Neonatal Screening tyrosinemia type I hereditary tyrosinemia newborn screening succinylacetone Tyrosine |
| title | The Importance of Succinylacetone: Tyrosinemia Type I Presenting with Hyperinsulinism and Multiorgan Failure Following Normal Newborn Screening |
| title_full | The Importance of Succinylacetone: Tyrosinemia Type I Presenting with Hyperinsulinism and Multiorgan Failure Following Normal Newborn Screening |
| title_fullStr | The Importance of Succinylacetone: Tyrosinemia Type I Presenting with Hyperinsulinism and Multiorgan Failure Following Normal Newborn Screening |
| title_full_unstemmed | The Importance of Succinylacetone: Tyrosinemia Type I Presenting with Hyperinsulinism and Multiorgan Failure Following Normal Newborn Screening |
| title_short | The Importance of Succinylacetone: Tyrosinemia Type I Presenting with Hyperinsulinism and Multiorgan Failure Following Normal Newborn Screening |
| title_sort | importance of succinylacetone tyrosinemia type i presenting with hyperinsulinism and multiorgan failure following normal newborn screening |
| topic | tyrosinemia type I hereditary tyrosinemia newborn screening succinylacetone Tyrosine |
| url | https://www.mdpi.com/2409-515X/6/2/39 |
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