Preventive use of nitisinone in alkaptonuria

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, suppress...

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Bibliographic Details
Published in:Orphanet journal of rare diseases 2021-08, Vol.16 (1), p.1-343, Article 343
Main Authors: Wolffenbuttel, Bruce H. R, Heiner-Fokkema, M. Rebecca, van Spronsen, Francjan J
Format: Article
Language:English
Subjects:
Age
Alkaptonuria
Arthritis
Complications
Complications and side effects
Dioxygenase
Disease prevention
Drug dosages
Drug therapy
Enzymatic activity
Enzymes
Excretion
Letter to the Editor
Medical research
Medicine, Preventive
Nitisinone
Osteoarthritis
Pain
Patients
Personalized medicine
Prevention
Preventive health services
Quality of life
Questionnaires
Rare diseases
Tyrosine
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Summary: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.
ISSN:1750-1172
1750-1172
DOI:10.1186/s13023-021-01977-0