Service d'Endocrinologie, Diabétologie et Métabolisme et Centre de Référence des Maladies Héréditaires du Métabolisme, Hôpital Huriez, CHU de Lille, 59037 Lille, France.
Centre de Référence des Maladies Héréditaires du Métabolisme, Hôpital Necker-Enfants Malades, APHP, 149 rue de Sèvres, 75015 Paris, France.
Mol Genet Metab. 2023 Nov;140(3):107704. doi: 10.1016/j.ymgme.2023.107704. Epub 2023 Sep 29.
Phenylketonuria (PKU) is an inborn error of metabolism. When diagnosed late, it causes developmental delay or severe irreversible intellectual disability. This study aimed at evaluating the health status and healthcare consumption of late-diagnosed PKU patients in France.
This retrospective observational study used health insurance claims data from the French SNDS (Système National des Données de Santé) database, which contains data from over 66 million French inhabitants. Patients with PKU were identified between 2006 and 2018 by ICD-10 diagnosis codes E70.0 / E70.1 documented as a chronic condition (affection de longue durée - ALD) or in the inpatient setting. Patients with PKU were matched to controls by age, sex, and region. Patients with late-diagnosed PKU were defined as patients born before the nationwide implementation of newborn screening in France in 1972. Outcomes were analyzed for the year 2018.
In total, 3549 patients with PKU were identified in the database on January 1st, 2018. Of those, 3469 patients could be matched to 17,170 controls without PKU. Of these, 2175 patients were at least 16 years old of whom 647 patients were categorized as late-diagnosed. The late-diagnosed PKU patients suffered significantly more often from hypertension (60.9% vs. 50.4%, p < 0.0001), hypercholesterolemia (41.7% vs. 26.9%, p < 0.0001), diabetes (24.4% vs. 14.1%, p < 0.0001), depression (20.6% vs. 13.8%, p < 0.0001), ischemic heart disease (16.1% vs. 6.6%, p < 0.0001), obesity (7.9% vs. 2.5%, inpatient diagnoses only, p < 0.0001), and chronic kidney disease (5.2% vs. 1.3%, inpatient diagnoses only, p < 0.0001) compared with their non-PKU controls. Consequently, significantly more patients with late-diagnosed PKU received medication to treat comorbidities associated with the nervous (82.6% vs 77.0%; p = 0.0021) and cardiovascular system (69.5% vs 58.0%; p < 0.0001). Overall, only 3.4% of patients with late-diagnosed PKU received dietary amino-acid supplements and 0.7% received sapropterin.
The results indicate that PKU is associated with a significantly higher risk of comorbidities along with increased pharmaceutical prescriptions in patients with late-diagnosed PKU, compared with non-PKU controls. The increased risk of comorbidities was more pronounced than in patients with early-diagnosed PKU, as shown in previous research, but these patients are older than those with early-diagnosed PKU. Only few late-diagnosed patients were treated specifically for PKU. Patients with late-diagnosed PKU should be referred to specialized centers to prevent and manage comordities and introduce PKU-specific treatment when it is possible.
苯丙酮尿症（PKU）是一种先天性代谢缺陷。如果诊断较晚，会导致发育迟缓或严重的不可逆转的智力残疾。本研究旨在评估法国迟发型 PKU 患者的健康状况和医疗保健消费。
本回顾性观察研究使用了法国 SNDS（国家健康数据系统）数据库中的健康保险索赔数据，该数据库包含了超过 6600 万法国居民的数据。通过 ICD-10 诊断代码 E70.0/E70.1 将 2006 年至 2018 年期间确诊为慢性疾病（ALD）或住院患者的 PKU 患者识别出来。通过年龄、性别和地区与 PKU 患者相匹配的对照患者。迟发型 PKU 患者被定义为在法国于 1972 年全国范围内实施新生儿筛查之前出生的患者。对 2018 年的结果进行了分析。
在数据库中，截至 2018 年 1 月 1 日，共发现 3549 例 PKU 患者。其中 3469 例患者可与 17170 例无 PKU 的对照患者相匹配。在这些患者中，有 2175 例患者年龄至少为 16 岁，其中 647 例患者被归类为迟发型。迟发型 PKU 患者患高血压的比例显著更高（60.9%对 50.4%，p<0.0001）、高胆固醇血症（41.7%对 26.9%，p<0.0001）、糖尿病（24.4%对 14.1%，p<0.0001）、抑郁症（20.6%对 13.8%，p<0.0001）、缺血性心脏病（16.1%对 6.6%，p<0.0001）、肥胖症（7.9%对 2.5%，仅住院诊断，p<0.0001）和慢性肾病（5.2%对 1.3%，仅住院诊断，p<0.0001）与非 PKU 对照患者相比。因此，与非 PKU 对照患者相比，接受治疗相关神经和心血管系统合并症的药物治疗的迟发型 PKU 患者明显更多（82.6%对 77.0%；p=0.0021）。总体而言，只有 3.4%的迟发型 PKU 患者接受饮食氨基酸补充剂治疗，0.7%的患者接受 sapropterin 治疗。
与非 PKU 对照患者相比，迟发型 PKU 患者患合并症的风险显著更高，同时需要开具更多的药物处方。与之前的研究相比，迟发型 PKU 患者的合并症风险更为明显，但这些患者的年龄大于早发型 PKU 患者。只有少数迟发型患者接受了专门针对 PKU 的治疗。迟发型 PKU 患者应转介至专门中心，以预防和管理合并症，并在可能时引入 PKU 特异性治疗。
