Recommendations for the management of tyrosinaemia type 1

Abstract

The management of tyrosinaemia type 1 (HT1, fumarylacetoacetase deficiency) has been revolutionised by the introduction of nitisinone but dietary treatment remains essential and the management is not easy. In this review detailed recommendations for the management are made based on expert opinion, published case reports and investigational studies as the evidence base is limited and there are no prospective controlled studies.The added value of this paper is that it summarises in detail current clinical knowledge about HT1 and makes recommendations for the management.

Infants with Tyrosinemia Type 1: Should phenylalanine be supplemented?

“…High tyrosine levels above the upper target of 400 mmol/L (de Laet et al 2013) led to further decrease of natural protein intake to a minimum of 0.5 g/kg/day (Fig. 1a, b).…”

“…Clinically, tyrosinemia type I (HT1; OMIM 276600, fumarylacetoacetase deficiency) is characterized by liver failure, hepatocellular carcinoma, renal tubulopathy, and porphyria-like syndrome (de Laet et al 2013). Implementation in neonatal blood spot screening (NBS) and treatment with 2-(2-nitro-4-trifluoromethyl-benzyl)-1,3-cyclohexanedione (NTBC) to prevent accumulation of toxic metabolites by inhibiting tyrosine catabolism upstream from the primary enzymatic defect has largely improved clinical outcome (Larochelle et al 2012;Mayorandan et al 2014).…”

What Is the Best Blood Sampling Time for Metabolic Control of Phenylalanine and Tyrosine Concentrations in Tyrosinemia Type 1 Patients?

“…Without treatment, patients develop liver failure, hepatocellular carcinoma, porphyria-like neurological episodes, renal tubulopathy, and cardiomyopathy (Mayorandan et al 2014). Increased blood and urine succinylacetone (SA) are diagnostic indicators (de Laet et al 2013).…”

“…Treatment of HT1 consists of the combination of prescription of NTBC (2-(2 nitro-4-3 trifluoro-methylben-zoyl)-1, 3-cyclohexanedione) and dietary restriction of phenylalanine (Phe) and tyrosine (Tyr) (de Laet et al 2013). NTBC has led to remarkable improvement in the outcome of HT1 (Larochelle et al 2012;de Laet et al 2013).…”

“…NTBC has led to remarkable improvement in the outcome of HT1 (Larochelle et al 2012;de Laet et al 2013). It inhibits the enzyme 4-hydroxyphenylpyruvate dioxygenase at a stage before the metabolic defect, but increases tyrosine concentrations as a consequence, necessitating a diet restriction of tyrosine and its indispensable precursor phenylalanine.…”