Abstract
Nitisinone, although unapproved for use in alkaptonuria (AKU), is currently the only homogentisic acid lowering therapy with a potential to modify disease progression in AKU. Therefore, safe use of nitisinone off-label requires identifying and managing tyrosine keratopathy. A 22-year-old male with AKU commenced 2 mg daily nitisinone after full assessment. He was issued an alert card explaining potential ocular symptoms such as red eye, tearing, ocular pain and visual impairment and how to manage them. On his first and second annual follow-up visits to the National Alkaptonuria Centre (NAC), there was no corneal keratopathy on slit lamp examination. On his third follow-up annual visit to the NAC, he was found to have typical dendritiform corneal keratopathy in both eyes which was asymptomatic. Nitisinone was suspended until a repeat slit lamp examination, 2 weeks later, confirmed that the keratopathy had resolved. He recommenced nitisinone 2 mg daily with a stricter low protein diet. On his fourth annual follow-up visit to the NAC, a routine slit lamp examination showed mild corneal keratopathy in the left eye. This is despite him reporting no ocular symptoms. This case highlights the fact that corneal keratopathy can occur without symptoms and any monitoring plan with off-label use of nitisinone in AKU will need to take this possibility into account. This is also the first time that typical corneal keratopathy has been described with the use of low dose nitisinone in AKU without symptoms.
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Communicated by: Pascale de Lonlay
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Take Home Message
Asymptomatic tyrosine keratopathy may occur in AKU patients taking low dose nitisinone. It can be detected using elective and symptom-based slit lamp examination and it should be managed by a metabolic physician and a specialised dietitian.
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Conflict of Interest
M. Khedr, S. Judd, M. C. Briggs, A. T. Hughes, A. M. Milan, R. M. K. Stewart, E. A. Lock, J. A. Gallagher and L. R. Ranganath declare that they have no conflict of interest.
Informed Consent
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.
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This article does not contain any studies with human or animal subjects performed by the any of the authors.
Details of the Contributions of Individual Authors
M. Khedr wrote the first draft.
S. Judd carried out dietary assessments.
A. T. Hughes, A. M. Milan, M. C. Briggs, R. M. K. Stewart, E. A. Lock, J. A. Gallagher and L. R. Ranganath: Intellectual input and support, editing the manuscript.
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M. Khedr.
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L. R. Ranganath.
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Details of Ethics Approval
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. In addition, the institutional review body (Royal Liverpool University Hospital) explicitly approved the National Alkaptonuria Service from which this data was generated.
A Patient Consent Statement
Informed consent was obtained from all patients for being included in the study. This is being published as a clinical practice article and standard research ethics process is not therefore appropriate. The data from this patient have been completely anonymised to ensure he is not recognised from the publication of this manuscript. The data obtained were following standard clinical assessments upon referral to the National Alkaptonuria Service in Liverpool. Patients are informed verbally and through being handwritten materials about the activities of the National AKU Service. They are explicitly informed in the Patient information booklet of the National AKU Service that:
We could publish results from the study but if we do, we will make sure you cannot be identified in any way. All data used for publicity or for other research purposes will ensure total anonymity. Please let us know when you are visiting Ward 9 B (where the National AKU Service is located) that you understand this and have no objection to it.
All the ocular photos were acquired during the standard assessments during the patient visit.
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© 2017 Society for the Study of Inborn Errors of Metabolism (SSIEM)
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Khedr, M. et al. (2017). Asymptomatic Corneal Keratopathy Secondary to Hypertyrosinaemia Following Low Dose Nitisinone and a Literature Review of Tyrosine Keratopathy in Alkaptonuria. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 40. JIMD Reports, vol 40. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2017_62
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DOI: https://doi.org/10.1007/8904_2017_62
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