Clinical and genetic characteristics of two patients with tyrosinemia type 1 in Slovenia – a novel fumarylacetoacetate hydrolase (FAH) intronic disease-causing variant

Šikonja, Jaka (author), Brecelj, Jernej (author), Žerjav-Tanšek, Mojca (author), Repič-Lampret, Barbka (author), Drole Torkar, Ana (author), Klemenčič, Simona (author), Lipovec, Neža (author), Stefanova Kralj, Valentina (author), Bertok, Sara (author), Kovač, Jernej (author), Faganel Kotnik, Barbara (author), Tesařová, Markéta (author), Remec, Žiga Iztok (author), Debeljak, Maruša (author), Battelino, Tadej (author), Grošelj, Urh (author)

Tyrosinemia type 1 (HT1) is an inborn error of tyrosine catabolism that leads to severe liver, kidney, and neurological dysfunction. Newborn screening (NBS) can enable a timely diagnosis and early initiation of treatment. We presented the follow up of the only two Slovenian patients diagnosed with HT1. Metabolic control was monitored by measuring tyrosine, phenylalanine and succinylacetone from dried blood spots (DBSs). Retrograde screening of HT1 was performed from DBSs taken at birth using tandem mass spectrometry. First patient was diagnosed at the age of 6 months in the asymptomatic phase due to an abnormal liver echogenicity, the other presented at 2.5 months with an acute liver failure and needed a liver transplantation. The first was a compound heterozygote for a novel FAH intronic variant c.607-21A>G and c.192G>T whereas the second was homozygous for c.192G>T. At the non-transplanted patient, 66% of tyrosine and 79% of phenylalanine measurements were in strict reference ranges of 200–400 μmol/L and >30 μmol/L, respectively, which resulted in a favorable cognitive outcome at 3.6 years. On retrograde screening, both patients had elevated SA levels; on the other hand, tyrosine was elevated only at one. We showed that non-coding regions should be analyzed when clinical and biochemical markers are characteristic of HT1. DBSs represent a convenient sample type for frequent amino acid monitoring. Retrograde diagnosis of HT1 was possible after more than three years of birth with SA as a primary marker, complemented by tyrosine.

• Language: English
• Keywords: tyrosinemia, fumarylacetoacetate hydrolase, nitisinone, dried blood spot, succinylacetone, intronic variant
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2022
• Number of pages: 7 str.
• Numbering: Vol. 30, art. 100836
• PID: 20.500.12556/RUL-138896
• UDC: 616-053.2:577.122.5
• ISSN on article: 2214-4269
• DOI: 10.1016/j.ymgmr.2021.100836
• COBISS.SI-ID: 90521859
• Publication date in RUL: 24.08.2022

Record is a part of a journal

• Title: Molecular genetics and metabolism reports
• Publisher: Elsevier
• ISSN: 2214-4269
• COBISS.SI-ID: 520387097

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: pediatrija, tirozenemija, presejalno testiranje