Evaluating the aortic stenosis phenotype before and after the effect of homogentisic acid lowering therapy: Analysis of a large cohort of eighty-one alkaptonuria patients,Molecular Genetics and Metabolism

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Evaluating the aortic stenosis phenotype before and after the effect of homogentisic acid lowering therapy: Analysis of a large cohort of eighty-one alkaptonuria patients
Molecular Genetics and Metabolism ( IF 3.8 ) Pub Date : 2021-05-21 , DOI: 10.1016/j.ymgme.2021.05.007
L R Ranganath ₁ , T Heseltine ₂ , M Khedr ₁ , M F Fisher ₂

Affiliation

Aims

A large alkaptonuria (AKU) cohort was studied to better characterise the poorly understood phenotype of aortic stenosis of rare disease AKU.

Methods and results

Eighty-one patients attended the National Alkaptonuria Centre (NAC) between 2007 and 2020. Nine only attended once. Fifty-one attended more than once and received nitisinone 2 mg daily. Twenty-one attended at least twice without receiving nitisinone. Assessments included questionnaire analysis, standard transthoracic echocardiography, as well as photographs of ochronotic pigment in eyes and ears at baseline when 2 mg nitisinone was commenced, and yearly thereafter. Blood and urine samples were collected for chemical measurement.

The prevalence of aortic stenosis and aortic valve replacement were 22.2 and 6.2% in the current group. Aortic maximum velocity (Vmax) was directly related to varying degrees to age (R = 0.58, p < 0.001), systolic blood pressure (R = 0.32, p < 0.05), serum homogentisic acid (sHGA) (R = 0.28, p < 0.05), ochronosis scores (R = 0.72, p < 0.001), and alkaptonuria severity score index (AKUSSI) (R = 0.58, p < 0.001) on linear regression analysis. Age and ochronosis scores were significantly related to Vmax on multiple regression analysis (p < 0.005). Nitisinone decreased sHGA, 24-h urine HGA (uHGA₂₄₎, ochronosis scores and AKUSSI significantly at all visits post-nitisinone. Nitisinone decreased Vmax change scores at final visit comparison, with a similar pattern at earlier visits.

Conclusion

Aortic valve disease is highly prevalent in this NAC cohort, and strongly associated with ochronosis and disease severity. Nitisinone decreases ochronosis and had a similar significant effect on Vmax.

中文翻译：

评估高黑酸降低治疗效果前后的主动脉瓣狭窄表型：对 81 名白尿症患者的大型队列分析

目标

研究了一个大型尿酸 (AKU) 队列，以更好地表征罕见病 AKU 主动脉瓣狭窄的知之甚少的表型。

方法和结果

2007 年至 2020 年期间，有 81 名患者参加了国家尿毒症中心 (NAC)。9 名患者仅参加过一次。51 人参加了不止一次，每天服用 2 毫克尼替西农。21 人参加了至少两次但未服用尼替西农。评估包括问卷分析、标准经胸超声心动图，以及在开始使用 2 mg 尼替西农时以及之后每年的基线时眼睛和耳朵中的非时变色素照片。收集血液和尿液样本用于化学测量。

本组主动脉瓣狭窄和主动脉瓣置换的患病率分别为22.2%和6.2%。主动脉最大流速（Vmax）与年龄（R = 0.58，p < 0.001）、收缩压（R = 0.32，p < 0.05）、血清高黑酸（sHGA）（R = 0.28，p < 0.05)、失时评分 ( R = 0.72, p < 0.001) 和尿酸严重评分指数 (AKUSSI) ( R = 0.58, p < 0.001) 线性回归分析。在多元回归分析中，年龄和黄褐斑评分与 Vmax 显着相关 ( p < 0.005)。尼替西农降低 sHGA、24 小时尿 HGA (uHGA₂₄₎，在尼替西农后的所有访视中，黄褐斑评分和 AKUSSI 显着。Nitisinone 在最终访问比较中降低了 Vmax 变化分数，在早期访问中具有类似的模式。