Clinical burden of illness in patients with phenylketonuria (PKU) and associated comorbidities - a retrospective study of German health insurance claims data

Abstract

Background 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. Methods 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. Results 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%). Conclusion 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). Electronic supplementary material The online version of this article (10.1186/s13023-019-1153-y) contains supplementary material, which is available to authorized users.

Special Low Protein Foods in the UK: An Examination of Their Macronutrient Composition in Comparison to Regular Foods

“…Over 30% of SLPF subgroups contained more salt than regular foods, with some containing 100-1050% extra. It is possible that their habitual consumption may contribute to nutritional co-morbidities such as hypertension [32][33][34], vascular stiffness [34,35], overweight/obesity [3,34,[36][37][38][39][40] and an atherogenic lipoprotein profile [34].…”

Phenylketonuria, co‐morbidity, and ageing: A review

“…Nonetheless, the literature currently leaves several intriguing questions (Box ). Relevant is a very recent study of German Insurance claims, including AwPKU (aged range 18‐96 years) and matched controls . 43% were early treated, though not all remained on diet, and few were receiving BH4.…”

Biological Responses to the Consumption of Non-Nutritional Sweeteners

“…Infants are diagnosed with PKU shortly after birth and avoiding aspartame is achieved well by patients throughout life [31]. However, people with PKU do show increased oxidative stress [32] and the presence of comorbidities including asthma, alopecia, urticaria, gallbladder disease, rhinitis, esophageal disorders, anemia, overweight, GERD, eczema, renal insufficiency, osteoporosis, gastritis/esophagitis and kidney stones [33]. Methanol, which is converted to formaldehyde (a known carcinogen) [34], is often pointed to as a reason to avoid aspartame, but higher levels of methanol are consumed when eating fruit [35,36].…”

“…Sucralose was found to promote fat accumulation and upregulate adipogenesis, inflammation, and antioxidant pathways [71]. While rodents lacking sweet taste receptor subunits were shown to have less adiposity and smaller adipocytes on a Western diet [32], showing the importance of sweet taste receptor signaling for normal adipose tissue development. One study suggested NNS's were not dependent on sweet taste receptors to stimulate adipogenesis or suppress lipolysis [36].…”