Reversal of ochronotic pigmentation in alkaptonuria following nitisinone therapy: Analysis of data from the United Kingdom National Alkaptonuria Centre
Abstract Background Increased homogentisic acid (HGA) causes ochronosis. Nitisinone decreases HGA. The aim was to study the effect of nitisinone on the ochronosis progression. Methods Photographs of the eyes and ears were acquired from patients attending the National Alkaptonuria Centre (NAC) at V‐1...
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doaj-39244242ead74ac28b7788233f9487512020-11-25T03:41:46ZengWileyJIMD Reports2192-83122020-09-01551758710.1002/jmd2.12137Reversal of ochronotic pigmentation in alkaptonuria following nitisinone therapy: Analysis of data from the United Kingdom National Alkaptonuria CentreLakshminarayan R. Ranganath0Anna M. Milan1Andrew T. Hughes2Milad Khedr3Andrew S. Davison4Peter J. Wilson5Jane P. Dillon6Elizabeth West7James A. Gallagher8Department of Clinical Biochemistry and Metabolic Medicine Royal Liverpool University Hospital Liverpool UKDepartment of Clinical Biochemistry and Metabolic Medicine Royal Liverpool University Hospital Liverpool UKDepartment of Clinical Biochemistry and Metabolic Medicine Royal Liverpool University Hospital Liverpool UKDepartment of Clinical Biochemistry and Metabolic Medicine Royal Liverpool University Hospital Liverpool UKDepartment of Clinical Biochemistry and Metabolic Medicine Royal Liverpool University Hospital Liverpool UKInstitute of Ageing and Chronic Disease, Musculoskeletal Biology I, William Henry Duncan Building Liverpool UKInstitute of Ageing and Chronic Disease, Musculoskeletal Biology I, William Henry Duncan Building Liverpool UKDepartment of ENT Broadgreen Hospital Liverpool UKInstitute of Ageing and Chronic Disease, Musculoskeletal Biology I, William Henry Duncan Building Liverpool UKAbstract Background Increased homogentisic acid (HGA) causes ochronosis. Nitisinone decreases HGA. The aim was to study the effect of nitisinone on the ochronosis progression. Methods 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. Results 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 (P < .01), followed by a decrease at V1, V2, and V3, in the VAR group (P < .01). Ochronotic pigment in ear biopsy between V0 and V4 showed a 19.1% decrease (P < .05). Conclusions Nitisinone decreases HGA and partially reverses ochronosis.https://doi.org/10.1002/jmd2.12137alkaptonurianitisinonehomogentisic acideye ochronosisear ochronosisear cartilage biopsy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lakshminarayan R. Ranganath Anna M. Milan Andrew T. Hughes Milad Khedr Andrew S. Davison Peter J. Wilson Jane P. Dillon Elizabeth West James A. Gallagher |
spellingShingle |
Lakshminarayan R. Ranganath Anna M. Milan Andrew T. Hughes Milad Khedr Andrew S. Davison Peter J. Wilson Jane P. Dillon Elizabeth West James A. Gallagher Reversal of ochronotic pigmentation in alkaptonuria following nitisinone therapy: Analysis of data from the United Kingdom National Alkaptonuria Centre JIMD Reports alkaptonuria nitisinone homogentisic acid eye ochronosis ear ochronosis ear cartilage biopsy |
author_facet |
Lakshminarayan R. Ranganath Anna M. Milan Andrew T. Hughes Milad Khedr Andrew S. Davison Peter J. Wilson Jane P. Dillon Elizabeth West James A. Gallagher |
author_sort |
Lakshminarayan R. Ranganath |
title |
Reversal of ochronotic pigmentation in alkaptonuria following nitisinone therapy: Analysis of data from the United Kingdom National Alkaptonuria Centre |
title_short |
Reversal of ochronotic pigmentation in alkaptonuria following nitisinone therapy: Analysis of data from the United Kingdom National Alkaptonuria Centre |
title_full |
Reversal of ochronotic pigmentation in alkaptonuria following nitisinone therapy: Analysis of data from the United Kingdom National Alkaptonuria Centre |
title_fullStr |
Reversal of ochronotic pigmentation in alkaptonuria following nitisinone therapy: Analysis of data from the United Kingdom National Alkaptonuria Centre |
title_full_unstemmed |
Reversal of ochronotic pigmentation in alkaptonuria following nitisinone therapy: Analysis of data from the United Kingdom National Alkaptonuria Centre |
title_sort |
reversal of ochronotic pigmentation in alkaptonuria following nitisinone therapy: analysis of data from the united kingdom national alkaptonuria centre |
publisher |
Wiley |
series |
JIMD Reports |
issn |
2192-8312 |
publishDate |
2020-09-01 |
description |
Abstract Background Increased homogentisic acid (HGA) causes ochronosis. Nitisinone decreases HGA. The aim was to study the effect of nitisinone on the ochronosis progression. Methods 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. Results 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 (P < .01), followed by a decrease at V1, V2, and V3, in the VAR group (P < .01). Ochronotic pigment in ear biopsy between V0 and V4 showed a 19.1% decrease (P < .05). Conclusions Nitisinone decreases HGA and partially reverses ochronosis. |
topic |
alkaptonuria nitisinone homogentisic acid eye ochronosis ear ochronosis ear cartilage biopsy |
url |
https://doi.org/10.1002/jmd2.12137 |
work_keys_str_mv |
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