Confocal Microscopy of Corneal Crystals in a Patient With Hereditary Tyrosinemia Type I, Treated With NTBC

Schauwvlieghe, Pieter-Paul; Jaeken, Jaak; Kestelyn, Philippe; Claerhout, Ilse

doi:10.1097/ico.0b013e318243e474

Cited by 13 publications

(17 citation statements)

References 9 publications

(8 reference statements)

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“…This may be consistent with the diurnal variation in the circulating tyrosine, known to be higher late in the day and lowest first thing in the morning (Fernstrom et al 1979). A similar diurnal variation in ocular pain in the evenings has been reported previously (Schauwvlieghe et al 2012). The symptoms on alternate days could be explained by the nitisinone dosing on alternate days; he could clarify whether his symptoms were on the day of administering nitisinone or the following.…”

Section: Discussionsupporting

confidence: 88%

Reversible Keratopathy Due to Hypertyrosinaemia Following Intermittent Low-Dose Nitisinone in Alkaptonuria: A Case Report

et al. 2014

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We describe a patient with ultra-rare disease, alkaptonuria, who developed tyrosine keratopathy following nitisinone therapy of 2 mg on alternate days. His vision became impaired approximately 7 weeks following the commencement of nitisinone and ophthalmological examination at week nine showed characteristic dendritic keratopathy associated with tyrosinaemia. The corneal lesion as well as his visual symptoms normalized completely following discontinuation of nitisinone. This is the first documented report of keratopathy due to acquired tyrosinaemia due to very low-dose nitisinone.

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Section: Discussionsupporting

confidence: 88%

Reversible Keratopathy Due to Hypertyrosinaemia Following Intermittent Low-Dose Nitisinone in Alkaptonuria: A Case Report

et al. 2014

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“…In that report, Schauwvlieghe et al confirmed the presence of slender birefringent spiky crystals in the superficial corneal epithelium with confocal microscopy. 11 Unlike the patient reported previously by Ahmad et al, despite stopping the NTBC treatment and the lack of the corneal symptoms, their case still experienced a relatively high tyrosine level of 650 mmol/L. Despite the decrease in tyrosine levels and the complete resolution of the corneal findings with dietary restrictions, our case also still manifested elevated tyrosine levels.…”

Section: Discussioncontrasting

confidence: 79%

Corneal Pseudodendritic Lesions Masquerading as Herpetic Keratitis in a Patient With Tyrosinemia Type I

Sevim

Gümüş

Cavanagh

2017

Eye &Amp; Contact Lens: Science &Amp; Clinical Practice

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“…Ocular involvement is not frequent in HT1 patients, but in those rare cases corneal keratitis is the main manifestation (31, 32). This has been attributed to inflammation produced by local tyrosine deposition in the form of crystals caused by low compliance with a low protein diet and the secondary effect of using NTBC on tyrosine accumulation.…”

Section: Resultsmentioning

confidence: 99%

“…Ocular involvement is rare in patients with HT1 but frequent in patients with tyrosinemia type II (46), which is produced by mutations in tyrosine transaminase, the enzyme undertaking the first step of tyrosine catabolism. As with tyrosinemia type II, corneal keratitis in HT1 patients and possibly FAH knock-out rabbits as well is caused by enhanced local accumulation of tyrosine, which is boosted by NTBC (31, 32). The frequency with which ocular manifestations happen in FAH −/− rabbits potentially makes them a useful model for studying how to prevent and treat this potential complication in HT1 patients.…”

Section: Discussionmentioning

confidence: 99%

Fumarylacetoacetate Hydrolase Knock-out Rabbit Model for Hereditary Tyrosinemia Type 1

Zhang

Yang

et al. 2017

Journal of Biological Chemistry

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Hereditary tyrosinemia type 1 (HT1) is a severe human autosomal recessive disorder caused by the deficiency of fumarylacetoacetate hydroxylase (FAH), an enzyme catalyzing the last step in the tyrosine degradation pathway. Lack of FAH causes accumulation of toxic metabolites (fumarylacetoacetate and succinylacetone) in blood and tissues, ultimately resulting in severe liver and kidney damage with onset that ranges from infancy to adolescence. This tissue damage is lethal but can be controlled by administration of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), which inhibits tyrosine catabolism upstream of the generation of fumarylacetoacetate and succinylacetone. Notably, in animals lacking FAH, transient withdrawal of NTBC can be used to induce liver damage and a concomitant regenerative response that stimulates the growth of healthy hepatocytes. Among other things, this model has raised tremendous interest for the in vivo expansion of human primary hepatocytes inside these animals and for exploring experimental gene therapy and cell-based therapies. Here, we report the generation of FAH knock-out rabbits via pronuclear stage embryo microinjection of transcription activator-like effector nucleases. FAH−/− rabbits exhibit phenotypic features of HT1 including liver and kidney abnormalities but additionally develop frequent ocular manifestations likely caused by local accumulation of tyrosine upon NTBC administration. We also show that allogeneic transplantation of wild-type rabbit primary hepatocytes into FAH−/− rabbits enables highly efficient liver repopulation and prevents liver insufficiency and death. Because of significant advantages over rodents and their ease of breeding, maintenance, and manipulation compared with larger animals including pigs, FAH−/− rabbits are an attractive alternative for modeling the consequences of HT1.

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Confocal Microscopy of Corneal Crystals in a Patient With Hereditary Tyrosinemia Type I, Treated With NTBC

Abstract: This is the first in vivo demonstration by confocal microscopy of corneal crystals present in a patient with proven type I tyrosinemia, under NTBC treatment.

Cited by 13 publications

References 9 publications

Reversible Keratopathy Due to Hypertyrosinaemia Following Intermittent Low-Dose Nitisinone in Alkaptonuria: A Case Report

Reversible Keratopathy Due to Hypertyrosinaemia Following Intermittent Low-Dose Nitisinone in Alkaptonuria: A Case Report

Corneal Pseudodendritic Lesions Masquerading as Herpetic Keratitis in a Patient With Tyrosinemia Type I

Fumarylacetoacetate Hydrolase Knock-out Rabbit Model for Hereditary Tyrosinemia Type 1

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