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Old treatments for new insights and strategies: proposed management in adults and children with alkaptonuria
Author(s) -
Arnoux JeanBaptiste,
Le Quan Sang KimHanh,
Brassier Anais,
Grisel Coraline,
Servais Aude,
Wippf Julien,
Dubois Sandrine,
Sireau Nicolas,
JobDeslandre Chantal,
Ranganath Lakshminarayan,
Lonlay Pascale
Publication year - 2015
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-015-9844-6
Subject(s) - alkaptonuria , ochronosis , medicine , asymptomatic , disease , enzyme replacement therapy , pathophysiology , aminoaciduria , dermatology , surgery , pathology , urine
Alkaptonuria (AKU) is caused by deficiency of the enzyme homogentisate 1,2 dioxygenase. It results in an accumulation of homogentisate which oxidizes spontaneously to benzoquinone acetate, a highly oxidant compound, which polymerises to a melanin‐like structure, in a process called ochronosis. Asymptomatic during childhood, this accumulation will lead from the second decade of life to a progressive and severe spondylo‐arthopathy, associated with multisystem involvement: osteoporosis/fractures, stones (renal, prostatic, gall bladder, salivary glands), ruptures of tendons/muscle/ligaments, renal failure and aortic valve disease. The pathophysiological mechanisms of AKU remain poorly understood, but recent advances lead us to reconsider the treatment strategy in AKU patients. Besides the supporting therapies (pain killers, anti‐inflammatory drugs, physiotherapy, joints replacements and others), specific therapies have been considered (anti‐oxidant, low protein diet, nitisinone), but clinical studies have failed to prove efficiency on the rheumatological lesions of the disease. Here we propose a treatment strategy for children and adults with AKU, based on a review of the latest findings on AKU and lessons from other aminoacipathies, especially tyrosinemias.