Ranganath, Lakshminarayan, Khedr, Milad, Milan, Anna M, Davison, Andrew S, Norman, Brendan P, Janssen, Mirian CH, Lock, Edward, Bou‐Gharios, George and Gallagher, James A
(2023)
Increased prevalence of Parkinson's disease in alkaptonuria.
JIMD Reports, 64 (4).
pp. 282-292.
Abstract
Amongst a cohort of 88 alkaptonuria (AKU) patients attending the United Kingdom National Alkaptonuria Centre (NAC), four unrelated patients had co-existing Parkinson's disease (PD). Two of the NAC patients developed PD before receiving nitisinone (NIT) while the other two developed overt PD during NIT therapy. NIT lowers redox-active homogentisic acid (HGA) and profoundly increases tyrosine (TYR). A further unpublished case of a Dutch patient with AKU and PD on deep brain stimulation is included in this report. A Pubmed search revealed a further five AKU patients with PD, all without NIT usage. The prevalence of PD in AKU in the NAC appears to be nearly 20-times higher than in the non-AKU population (<i>p</i> < 0.001) even when adjusted for age. We propose that life-long exposure to redox-active HGA may account for the higher prevalence of PD in AKU. Furthermore, the appearance of PD in AKU patients during NIT therapy may be due to unmasking dopamine deficiency in susceptible individuals, as a result of the tyrosinaemia during NIT therapy inhibiting the rate-limiting brain tyrosine hydroxylase.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Parkinson's disease, alkaptonuria, homogentisic acid, nitisinone, oxidative stress, tyrosine |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 25 May 2023 10:14 |
| Last Modified: | 07 Jul 2023 05:38 |
| DOI: | 10.1002/jmd2.12367 |
| Open Access URL: | https://doi.org/10.1002/jmd2.12367 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3170679 |
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