Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Heidelberg, Heidelberg, Germany.
University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Orphanet J Rare Dis. 2019 Jul 22;14(1):181. doi: 10.1186/s13023-019-1153-y.
Phenylketonuria (PKU) is an inherited deficiency in the enzyme phenylalanine hydroxylase (PAH), which, when poorly-managed, is associated with clinical features including deficient growth, microcephaly, seizures, and intellectual impairment. The management of PKU should start as soon as possible after diagnosis to prevent irreversible damage and be maintained throughout life. The aim of this study was to assess the burden of illness in PKU patients in general and in PKU patients born before and after the introduction of newborn screening in Germany.
This retrospective matched cohort analysis used the Institut für angewandte Gesundheitsforschung Berlin (InGef) research database containing anonymized healthcare claims of approximately 4 million covered lives. PKU patients were compared with matched controls from the general population within the same database (1:10 ratio via direct, exact matching on age and gender without replacement). PKU patients were included if they were aged ≥18 years on 01/01/15 and were continuously enrolled from 01/01/10 to 31/12/15. The 50 most commonly reported comorbidities and 50 most commonly prescribed medications in the PKU population were analyzed. Differences between groups were tested using 95% confidence interval (CI) of prevalence ratio (PR) values.
The analysis included 377 adult PKU patients (< 5 of which were receiving sapropterin dihydrochloride) and 3,770 matched controls. Of the 50 most common comorbidities in the PKU population, those with a statistically significant PR > 1.5 vs controls included major depressive disorders (PR = 2.3), chronic ischemic heart disease (PR = 1.7), asthma (PR = 1.7), dizziness and giddiness (PR = 1.8), unspecified diabetes mellitus (PR = 1.7), infectious gastroenteritis and colitis (PR = 1.7), and reaction to severe stress and adjustment disorders (PR = 1.6). The most commonly prescribed Anatomical Therapeutic Chemical (ATC) subcodes among PKU patients (vs the control population) are for systemic antibacterials (34.7% vs 32.8%), anti-inflammatory and antirheumatic (29.4% vs 27.5%), renin-angiotensin agents (30.0% vs 27.0%), acid-related disorders (29.4% vs 20.2%), and beta-blockers (24.9% vs 19.9%).
The overall clinical burden on patients with PKU is exacerbated by a significantly higher risk of numerous comorbidities and hence, prescribing of the requisite medication, both for recognized (e.g. major depressive disorders) and more unexpected comorbidities (e.g. ischemic heart disease).
苯丙酮尿症（PKU）是一种苯丙氨酸羟化酶（PAH）酶缺乏症，如果管理不善，会导致生长不良、小头畸形、癫痫和智力障碍等临床特征。PKU 的管理应在诊断后尽快开始，以防止不可逆转的损害，并在整个生命周期中维持。本研究旨在评估德国一般 PKU 患者和新生儿筛查前后出生的 PKU 患者的疾病负担。
这是一项回顾性匹配队列分析，使用柏林应用卫生研究协会（InGef）研究数据库，该数据库包含约 400 万被保险者的匿名医疗索赔数据。PKU 患者与数据库中相同人群的匹配对照（通过直接、年龄和性别精确匹配，无替换，1：10 比例）进行比较。如果患者在 2015 年 1 月 1 日年满 18 岁，并且在 2010 年 1 月 1 日至 2015 年 12 月 31 日期间持续入组，则将其纳入分析。分析了 PKU 人群中最常见的 50 种合并症和 50 种最常用的药物。使用患病率比（PR）值的 95%置信区间（CI）检验组间差异。
该分析纳入了 377 名成年 PKU 患者（其中<5 名患者接受 sapropterin dihydrochloride 治疗）和 3770 名匹配对照。在 PKU 人群中最常见的 50 种合并症中，与对照组相比，PR 值>1.5 的疾病包括重度抑郁症（PR=2.3）、慢性缺血性心脏病（PR=1.7）、哮喘（PR=1.7）、头晕和眩晕（PR=1.8）、未特指的糖尿病（PR=1.7）、传染性胃肠炎和结肠炎（PR=1.7）和严重应激及适应障碍反应（PR=1.6）。PKU 患者（与对照组相比）最常用的解剖治疗化学（ATC）亚码是全身性抗菌药物（34.7%比 32.8%）、抗炎和抗风湿药物（29.4%比 27.5%）、肾素-血管紧张素制剂（30.0%比 27.0%）、酸相关疾病（29.4%比 20.2%）和β-受体阻滞剂（24.9%比 19.9%）。
PKU 患者的整体临床负担因多种合并症的风险显著增加而加剧，因此需要开具必需的药物，包括已识别的（如重度抑郁症）和更意外的合并症（如缺血性心脏病）。
