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Review
. 2025 Jan;48(1):e12824.
doi: 10.1002/jimd.12824.

Diagnosis, treatment, management and monitoring of patients with tyrosinaemia type 1: Consensus group recommendations from the German-speaking countries

Anibh M Das  1 , Diana Ballhausen  2 , Dorothea Haas  3 , Johannes Häberle  4 , Tobias Hagedorn  5 , Cecilia Janson-Mutsaerts  5 , Nils Janzen  6   7 , Johannes Sander  6 , Peter Freisinger  8 , Daniela Karall  9 , Uta Meyer  1 , Eberhard Mönch  10 , Susanne Morlot  11 , Stefanie Rosenbaum-Fabian  12 , Sabine Scholl-Bürgi  9 , Stephan Vom Dahl  13 , Natalie Weinhold  14 , Jiri Zeman  15 , Karin Lange  16
Affiliations
Review

Diagnosis, treatment, management and monitoring of patients with tyrosinaemia type 1: Consensus group recommendations from the German-speaking countries

Anibh M Das et al. J Inherit Metab Dis. 2025 Jan.

Abstract

Hepatorenal tyrosinaemia (HT1) is an autosomal recessive disorder of tyrosine degradation resulting in hepatic and renal dysfunction, neurological sequelae may occur in some patients. The use of nitisinone (NTBC) has revolutionised treatment and outcome of this disorder. NTBC has to be combined with a low protein diet. While NTBC modulates the disease course in HT1 patients, several issues are open. Optimal dosage, doses per day, therapeutic range of NTBC concentration, mode of protein restriction and biomarkers are not well defined. HCC and neurocognitive deficits are long-term sequelae. Early diagnosis and treatment are essential to minimise the risk for these complications. Clinical guidance for management of HT1-patients is required. Randomised clinical studies are difficult in the presence of therapeutic options. We discussed these issues in a consensus group of 10 paediatricians, 1 adult hepatologist, 1 geneticist, 2 dieticians, 2 newborn screening specialists with experience in HT1, 1 psychologist and 2 representatives of a patient group from the German-speaking countries (DACH). Recommendations were based on scientific literature and expert opinion, also taking into account recent experience with newborn screening. There was strong consensus that newborn screening using succinylacetone (SA) and early treatment are essential for a good outcome. The dose of NTBC should be as low as possible without losing metabolic control. This has to be accompanied by a low protein diet, in some patients a simplified diet without calculation of protein intake. Specific education and psychosocial support are recommended. Indications for liver transplantation were defined. Monitoring shall include clinical findings, levels of SA, tyrosine, phenylalanine and NTBC in (dried) blood.

Keywords: hepatorenal tyrosinaemia; newborn screening; nitisinone; succinylacetone; tyrosine.

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Conflict of interest statement

Anibh M. Das, Diana Ballhausen, Dorothea Haas, Johannes Häberle, Tobias Hagedorn, Cecilia Janson‐Mutsaerts, Nils Janzen, Johannes Sander, Peter Freisinger, Daniela Karall, Uta Meyer, Eberhard Mönch, Susanne Morlot, Stefanie Rosenbaum‐Fabian, Sabine Scholl‐Bürgi, Stephan vom Dahl, Natalie Weinhold, Jiri Zeman, and Karin Lange declare that they have no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Diagnostic work‐up of a positive newborn screening result via newborn screening (left) or selective screening (right).
FIGURE 2
FIGURE 2
Degradation of tyrosine to fumarate and acetoacetate. FAH is deficient in HT1, nitisinone results in reduction of toxic metabolites, succinylacetone serves as a surrogate marker for toxicity.
See this image and copyright information in PMC

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