BACKGROUND: Hepatorenal tyrosinaemia (Tyr 1) is a rare inborn error of tyrosine metabolism. Without treatment, patients are at high risk of developing acute liver failure, renal dysfunction and in the long run hepatocellular carcinoma. The aim of our study was to collect cross-sectional data. METHODS: Via questionnaires we collected retrospective data of 168 patients with Tyr 1 from 21 centres (Europe, Turkey and Israel) about diagnosis, treatment, monitoring and outcome. In a subsequent consensus workshop, we discussed data and clinical implications. RESULTS: Early treatment by NTBC accompanied by diet is essential to prevent serious complications such as liver failure, hepatocellular carcinoma and renal disease. As patients may remain initially asymptomatic or develop uncharacteristic clinical symptoms in the first months of life newborn mass screening using succinylacetone (SA) as a screening parameter in dried blood is mandatory for early diagnosis. NTBC-treatment has to be combined with natural protein restriction supplemented with essential amino acids. NTBC dosage should be reduced to the minimal dose allowing metabolic control, once daily dosing may be an option in older children and adults in order to increase compliance. Metabolic control is judged by SA (below detection limit) in dried blood or urine, plasma tyrosine (<400 μM) and NTBC-levels in the therapeutic range (20-40 μM). Side effects of NTBC are mild and often transient. Indications for liver transplantation are hepatocellular carcinoma or failure to respond to NTBC. Follow-up procedures should include liver and kidney function tests, tumor markers and imaging, ophthalmological examination, blood count, psychomotor and intelligence testing as well as therapeutic monitoring (SA, tyrosine, NTBC in blood). CONCLUSION: Based on the data from 21 centres treating 168 patients we were able to characterize current practice and clinical experience in Tyr 1. This information could form the basis for clinical practice recommendations, however further prospective data are required to underpin some of the recommendations.

Allgemeine Kinderheilkunde und Jugendmedizin Universitätsklinikum Freiburg Mathildenstr 1 D 79106 Freiburg Germany

Bambino Gesù Children's Hospital Piazza Sant'Onofrio 4 00165 Rome Italy

Birmingham Children's Hospital Steelhouse Ln Birmingham B4 6NH United Kingdom

Clinic for Paediatric Kidney Liver and Metabolic Diseases Hannover Medical School Carl Neuberg Str 1 D 30625 Hannover Germany

Department für Kinder und Jugendheilkunde Medizinische Universität Innsbruck Anichstrasse 35 A 6020 Innsbruck Austria

Department of Pediatrics 1st Faculty of Medicine Charles University Prague Ke Karlovu 2 Prague 2 128 08 Czech Republic

Dr von Haunersches Kinderspital Lindwurmstr 4 D 80337 München Germany

Hannover Medical School Clinic for Gastroenterology Hepatology and Endocrinology Carl Neuberg Str 1 D 30625 Hannover Germany

Hannover Medical School Institute for Biometry Carl Neuberg Str 1 D 30625 Hannover Germany

Hannover Medical School Institute for Cellular and Molecular Pathology Carl Neuberg Str 1 D 30625 Hannover Germany

Hospital universitario de Cruces Plaza de Cruces 12 48903 San Vicente de Barakaldo Spain

Institute of Clinical Pharmacology Hannover Medical School Carl Neuberg Str 1 D 30625 Hannover Germany

Istanbul University Faculty of Medicine Fatih Capa Istanbul 34093 Turkey

Klinik für Kinder und Jugendmedizin Steinenbergstr 31 D 72764 Reutlingen Germany

Medizinische Universität Graz Auenbruggerplatz 2 A 8036 Graz Austria

Oslo University Hospital P B 4950 Nydalen 0424 Oslo Norway

Pediatric Metabolic Disorders Rambam Medical center 6 Ha'Aliya Street Post Box No 9602 Haifa Haifa 31096 Israel

Queen Fabiola Children's University Hospital Avenue Crocq 15 B 1020 Brussels Belgium

Reference Center for Inherited Metabolic Diseases Hôpital Robert Debré APHP 48 Boulevard Sérurier F 75019 Paris France

Screening Labor Hannover Am Steinweg 11A 13B D 30952 Ronnenberg Benthe Germany

Section of Metabolic Diseases Beatrix Children's Hospital University Medical Center Groningen University of Groningen Hanzeplein 1 9713 GZ Groningen The Netherlands

Unidad de Enfermedades Metabólicas Congénitas Hospital Clínico Universitario Santiago de Compostela Travesía de Choupana s n 15706 Santiago de Compostela Spain

Universitätsklinik für Kinder und Jugendheilkunde Währinger Gürtel 18 20 1090 Wien Austria

Universitätsklinik für Kinderheilkunde Inselspital Freiburgstrasse 7 CH 3010 Bern Switzerland

Universitätsklinikum Düsseldorf Moorenstr 5 D 40225 Düsseldorf Germany

Universitätsklinikum Hamburg Eppendorf Klinik und Poliklinik für Kinder und Jugendmedizin Martinistr 52 D 20246 Hamburg Germany

Universitätspital Zürich Klinik für Endokrinologie Diabetologie und Klinische Ernährung Rämistrasse 100 CH 8091 Zürich Switzerland

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