Preventive use of nitisinone in alkaptonuria.
Alkaptonuria
Complications
Nitisinone
Personalized medicine
Prevention
Journal
Orphanet journal of rare diseases
ISSN: 1750-1172
Titre abrégé: Orphanet J Rare Dis
Pays: England
ID NLM: 101266602
Informations de publication
Date de publication:
03 08 2021
03 08 2021
Historique:
received:
17
05
2021
accepted:
25
07
2021
entrez:
4
8
2021
pubmed:
5
8
2021
medline:
7
10
2021
Statut:
epublish
Résumé
Alkaptonuria (AKU, OMIM 203500) is a rare congenital disorder caused by a deficiency of the enzyme homogentisate-1,2,-dioxygenase. The long-term consequences of AKU are joint problems, cardiac valve abnormalities and renal problems. Landmark intervention studies with nitisinone 10 mg daily, suppressing an upstream enzyme activity, demonstrated its beneficial effects in AKU patients with established complications, which usually start to develop in the fourth decade. Lower dose of nitisinone in the range of 0.2-2 mg daily will already reduce urinary homogentisic acid (uHGA) excretion by > 90%, which may prevent AKU-related complications earlier in the course of the disease while limiting the possibility of side-effects related to the increase of plasma tyrosine levels caused by nitisinone. Future preventive studies should establish the lowest possible dose for an individual patient, the best age to start treatment and also collect evidence to which level uHGA excretion should be reduced to prevent complications.
Identifiants
pubmed: 34344451
doi: 10.1186/s13023-021-01977-0
pii: 10.1186/s13023-021-01977-0
pmc: PMC8336241
doi:
Substances chimiques
Cyclohexanones
0
Nitrobenzoates
0
Tyrosine
42HK56048U
nitisinone
K5BN214699
Types de publication
Letter
Langues
eng
Sous-ensembles de citation
IM
Pagination
343Informations de copyright
© 2021. The Author(s).
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