Cross-sectional study of 168 patients with hepatorenal tyrosinaemia and implications for clinical practice

TY - JOUR

T1 - Cross-sectional study of 168 patients with hepatorenal tyrosinaemia and implications for clinical practice

AU - Mayorandan, Sebene

AU - Meyer, Uta

AU - Gokcay, Gülden

AU - Segarra, Nuria Garcia

AU - de Baulny, Hélène Ogier

AU - van Spronsen, Francjan

AU - Zeman, Jiri

AU - de Laet, Corinne

AU - Spiekerkoetter, Ute

AU - Thimm, Eva

AU - Maiorana, Arianna

AU - Dionisi-Vici, Carlo

AU - Moeslinger, Dorothea

AU - Brunner-Krainz, Michaela

AU - Lotz-Havla, Amelie Sophia

AU - Cocho de Juan, José Angel

AU - Couce Pico, Maria Luz

AU - Santer, René

AU - Scholl-Bürgi, Sabine

AU - Mandel, Hanna

AU - Bliksrud, Yngve Thomas

AU - Freisinger, Peter

AU - Aldamiz-Echevarria, Luis Jose

AU - Hochuli, Michel

AU - Gautschi, Matthias

AU - Endig, Jessica

AU - Jordan, Jens

AU - McKiernan, Patrick

AU - Ernst, Stefanie

AU - Morlot, Susanne

AU - Vogel, Arndt

AU - Sander, Johannes

AU - Das, Anibh Martin

PY - 2014/8/1

Y1 - 2014/8/1

N2 - 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.

AB - 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.

KW - Adolescent

KW - Child

KW - Child, Preschool

KW - Cross-Sectional Studies

KW - Cyclohexanones/adverse effects

KW - Enzyme Inhibitors/adverse effects

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Liver Failure/diagnosis

KW - Liver Transplantation

KW - Male

KW - Neonatal Screening/methods

KW - Nitrobenzoates/adverse effects

KW - Rare Diseases/diagnosis

KW - Renal Insufficiency/diagnosis

KW - Retrospective Studies

KW - Surveys and Questionnaires

KW - Treatment Outcome

KW - Tyrosinemias/diagnosis

KW - Young Adult

U2 - 10.1186/s13023-014-0107-7

DO - 10.1186/s13023-014-0107-7

M3 - SCORING: Journal article

C2 - 25081276

VL - 9

SP - 107

JO - ORPHANET J RARE DIS

JF - ORPHANET J RARE DIS

SN - 1750-1172

ER -