20.500.12556/RUL-138896 Clinical and genetic characteristics of two patients with tyrosinemia type 1 in Slovenia – a novel fumarylacetoacetate hydrolase (FAH) intronic disease-causing variant 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. tyrosinemia fumarylacetoacetate hydrolase nitisinone dried blood spot succinylacetone intronic variant pediatrija tirozenemija presejalno testiranje true false true Angleški jezik Slovenski jezik Članek v reviji 2022-08-24 14:03:52 2022-08-24 14:03:58 2022-09-15 04:17:21 0000-00-00 00:00:00 2022 0 0 7 str. Vol. 30, art. 100836 Mar. 2022 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616-053.2:577.122.5 2214-4269 10.1016/j.ymgmr.2021.100836 90521859 1-s2.0-S2214426921001312-main.pdf 1-s2.0-S2214426921001312-main.pdf 1 89885C12E64228FAE0D4B659B70830CC 1e053f33164243494ec6b843240082afe7c763f146371aa0d1aa6030cb4a9499 145eb21d-23a5-11ed-92af-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=159388 https://www.sciencedirect.com/science/article/pii/S2214426921001312 1 d020fedb-23a4-11ed-92af-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=159387 Medicinska fakulteta 0 0 0