Cross-sectional study of 168 patients with hepatorenal tyrosinaemia and implications for clinical practice
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RESEARCH
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Cross-sectional study of 168 patients with hepatorenal tyrosinaemia and implications for clinical practice Sebene Mayorandan1, Uta Meyer1, Gülden Gokcay2, Nuria Garcia Segarra3, Hélène Ogier de Baulny3, Francjan van Spronsen4, Jiri Zeman5, Corinne de Laet6, Ute Spiekerkoetter7, Eva Thimm8, Arianna Maiorana9, Carlo Dionisi-Vici9, Dorothea Moeslinger10, Michaela Brunner-Krainz11, Amelie Sophia Lotz-Havla12, José Angel Cocho de Juan13, Maria Luz Couce Pico13, René Santer14, Sabine Scholl-Bürgi15, Hanna Mandel16, Yngve Thomas Bliksrud17, Peter Freisinger18, Luis Jose Aldamiz-Echevarria19, Michel Hochuli20, Matthias Gautschi21, Jessica Endig22, Jens Jordan23, Patrick McKiernan24, Stefanie Ernst25, Susanne Morlot26, Arndt Vogel22, Johannes Sander27 and Anibh Martin Das1*
Abstract 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 ( A (IVS12 + 5G > A) homozygous (11 patients) and c. 5541G > T homozygous (13 patients). Using a retrospective study-design we could not find a genotype-phenotype correlation (both classifications of phenotype according to Halvorsen 1990 as well as according to van Spronsen 1994 were tested separately).
Mayorandan et al. Orphanet Journal of Rare Diseases 2014, 9:107 http://www.ojrd.com/content/9/1/107
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Table 1 Patients with a single symptom at diagnosis (100% = 40patients) Symptom
Patients (n)
%
Acute liver failure
17
42.5
Liver dysfunction: bleeding tendencies, elevated liver enzymes
7
17.5
Hepatomegaly
2
5.0
Cirrhosis
5
12.5
Nephromegaly
1
2.5
Renal tubular dysfunction
1
2.5
Growth retardation
3
7.5
Rickets
1
2.5
Renal dysfunction
3
7.5
AFP level of 41,487 μg/l ( +/− SD: 58,368 μg/l; median: 16,210 μg/l; range: 34–265,140 μg/l). At diagnosis, initial
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