| Title: |
Increased prevalence of Parkinson's disease in alkaptonuria. |
| Authors: |
Ranganath, L; Khedr, M; Milan, AM; Davison, AS; Norman, BP; Janssen, MCH; Lock, EA; Bou-Gharios, G; Gallagher, JA |
| Publisher Information: |
Wiley |
| Publication Year: |
2023 |
| Collection: |
Liverpool John Moores University: LJMU Research Online |
| Subject Terms: |
QH301 Biology; QR Microbiology |
| Description: |
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 A further unpublished case of a Dutch patient with AKU and PD on deep brain stimulation is included in this report.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 (p < 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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| ISSN: |
2192-8304 |
| Relation: |
https://researchonline.ljmu.ac.uk/id/eprint/20337/1/PMC10315388.pdf; Ranganath, L, Khedr, M, Milan, AM, Davison, AS, Norman, BP, Janssen, MCH, Lock, EA, Bou-Gharios, G and Gallagher, JA (2023) Increased prevalence of Parkinson's disease in alkaptonuria. JIMD reports, 64 (4). pp. 282-292. ISSN 2192-8304 |
| DOI: |
10.1002/jmd2.12367 |
| Availability: |
https://researchonline.ljmu.ac.uk/id/eprint/20337/; https://researchonline.ljmu.ac.uk/id/eprint/20337/1/PMC10315388.pdf; https://doi.org/10.1002/jmd2.12367 |
| Rights: |
cc_by |
| Accession Number: |
edsbas.B340AB46 |
| Database: |
BASE |