title: Renal function in tyrosinaemia type I after liver transplantation: a long-term follow-up.
abstract: Hereditary tyrosinaemia type I is an autosomal recessive inborn error of tyrosine catabolism caused by a deficiency of the enzyme fumarylacetoacetase that results in liver failure, hepatocellular carcinoma, renal tubular dysfunction and acute intermittent porphyria. When treated with liver transplantation, tyrosinaemia type I was considered to be cured. Some years after the first liver transplantations in these patients, some reports focused on the renal function after transplantation. These reports showed that urinary succinylacetone excretion remained but that tubular function normalized. In this report we discuss the long-term renal follow-up (mean follow-up time 11 years, range 7-14 years) after liver transplantation in 9 patients with tyrosinaemia type I treated by liver transplantation in our centre. An evaluation was made of renal function and succinylacetone excretion in urine. In all patients we found a persistent excretion of succinylacetone in the urine. With respect to the glomerular function, we can conclude that there is no clear change in GFR. At the same time, tubulopathy persisted in some patients. We consider that excretion of metabolites such as succinylacetone will be an important contributing factor to tubular dysfunction after liver transplantation in patients with tyrosinaemia type I. Therefore, notwithstanding the major effect of liver transplantation on tyrosine metabolism, renal tubular dysfunction remains at risk and needs careful monitoring. Progressive tubular dysfunction can cause glomerular damage. The use of low-dose NTBC might be considered after liver transplantation in case of tubulopathy to prevent progression of tubular and glomerular dysfunction.
authors.affiliation: Department of Pediatric Nephrology [corrected], Beatrix Childrens [corrected] Hospital, University Medical Center, Postbox 30.001, 9700RB, Groningen, The Netherlands, l.j.w.m.pierik@bkk.umcg.nl
authors.forename: L J W M
authors.initials: LJ
authors.lastname: Pierik
authors.forename: F J
authors.initials: FJ
authors.lastname: van Spronsen
authors.forename: C M A
authors.initials: CM
authors.lastname: Bijleveld
authors.forename: C M L
authors.initials: CM
authors.lastname: van Dael
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006537:Heptanoates / Q000652:urine; D006801:Humans; D007223:Infant; D007668:Kidney / Q000502:physiology* / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism; D020176:Tyrosinemias / Q000503:physiopathology* / Q000628:therapy*
chemical_list: D006537:Heptanoates; D014443:Tyrosine; C020804:succinylacetone