Reversal of ochronotic pigmentation in alkaptonuria following nitisinone therapy: Analysis of data from the United Kingdom National Alkaptonuria Centre.

Ranganath, Lakshminarayan R ORCID: 0000-0002-4205-2269, Milan, Anna M, Hughes, Andrew T, Khedr, Milad, Davison, Andrew S ORCID: 0000-0001-5501-4475, Wilson, Peter J, Dillon, Jane P ORCID: 0000-0002-7055-5664, West, Elizabeth and Gallagher, James A (2020) Reversal of ochronotic pigmentation in alkaptonuria following nitisinone therapy: Analysis of data from the United Kingdom National Alkaptonuria Centre. JIMD reports, 55 (1). pp. 75-87.

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Official URL: http://dx.doi.org/10.1002/jmd2.12137

Abstract

<h4>Background</h4>Increased homogentisic acid (HGA) causes ochronosis. Nitisinone decreases HGA. The aim was to study the effect of nitisinone on the ochronosis progression.<h4>Methods</h4>Photographs of the eyes and ears were acquired from patients attending the National Alkaptonuria Centre (NAC) at V-1 (pre-baseline visit), V0 (baseline visit when 2 mg nitisinone was commenced), and yearly at V1, V2, and V3 visits. Photographs were inspected for evolution of ochronotic pigment and also scored categorically to derive eye, ear, and combined ochronosis scores. An ear cartilage biopsy was also carried out at V0 and one year after V3 (V4) and ochronotic pigment was assessed and quantitated. Visits were compared for changes in pigment. Fasting blood and 24-hour urine samples were collected for measurement of HGA.<h4>Results</h4>There were 80 AKU patients at V0, and 52, 47, and 40 at V1, V2, and V3 in the group with variable numbers (VAR Group) respectively; 23 patients attended once before V0, in the V-1 visit. Photographs of patients show increase in eye pigment between V-1 and V0, followed by decrease post-nitisinone at V1, V2, and V3. Ear and combined ochronosis semiquantitative scoring showed an increase between V-1 and V0 (<i>P</i> < .01), followed by a decrease at V1, V2, and V3, in the VAR group (<i>P</i> < .01). Ochronotic pigment in ear biopsy between V0 and V4 showed a 19.1% decrease (<i>P</i> < .05).<h4>Conclusions</h4>Nitisinone decreases HGA and partially reverses ochronosis.

Item Type:	Article
Uncontrolled Keywords:	alkaptonuria, ear cartilage biopsy, ear ochronosis, eye ochronosis, homogentisic acid, natural history, nitisinone, reversal
Depositing User:	Symplectic Admin
Date Deposited:	27 Aug 2020 14:43
Last Modified:	18 Jan 2023 23:36
DOI:	10.1002/jmd2.12137
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3098792