Royal Liverpool University Hospital, Liverpool, UK.
Musculoskeletal Biology I, Institute of Ageing & Chronic Disease, William Henry Duncan Building, University of Liverpool, Liverpool, UK.
J Inherit Metab Dis. 2019 Sep;42(5):776-792. doi: 10.1002/jimd.12152. Epub 2019 Aug 5.
Ochronosis is the process in alkaptonuria (AKU) that causes all the debilitating morbidity. The process involves selective deposition of homogentisic acid (HGA)-derived pigment in tissues altering the properties of these tissues, leading to their failure. Some tissues like cartilage are more easily affected by ochronosis while others such as the liver and brain are unaffected for reasons that are still not understood. In vitro and mouse models of ochronosis have confirmed the dose relationships between HGA and ochronosis and also their modulation by p-hydroxyphenylpyruvate dioxygenase inhibition. Ochronosis cannot be fully reversed and is a key factor in influencing treatment decisions. Earlier detection of ochronosis preferably by noninvasive means is desirable. A cause-effect relationship between HGA and ochronosis is discussed. The similarity in AKU and familial hypercholesterolaemia is explored and lessons learnt. More research is needed to more fully understand the crucial nature of ochronosis.
奥克洛诺司病是一种尿黑酸症（AKU），会导致所有使人衰弱的发病率。该过程涉及到对同质型酸（HGA）衍生色素的选择性沉积，改变这些组织的特性，导致其功能衰竭。一些组织，如软骨，更容易受到奥克洛诺司病的影响，而其他组织，如肝脏和大脑，由于尚未明确的原因而不受影响。奥克洛诺司病的体外和小鼠模型证实了 HGA 和奥克洛诺司病之间的剂量关系，以及它们被对羟苯丙酮酸双加氧酶抑制的调节。奥克洛诺司病无法完全逆转，是影响治疗决策的关键因素。最好通过非侵入性手段尽早发现奥克洛诺司病。探讨了 HGA 与奥克洛诺司病之间的因果关系。探索了 AKU 和家族性高胆固醇血症之间的相似性，并吸取了经验教训。需要进行更多的研究，以更充分地了解奥克洛诺司病的关键性质。
