Comparison of atherogenic risk factors among poorly controlled and well-controlled adolescent phenylketonuria patients

Gündüz, Mehmet; Çakar, Sevim; Kuyum, Pınar; Makay, Balahan; Arslan, Nur

doi:10.1017/s104795111500150x

Cited by 12 publications

(17 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another study [20] in 59 patients with PKU and 44 healthy controls (11 to 17 years of age) found significantly lower levels of cardioprotective HDL cholesterol in well-controlled ( n = 24; blood Phe < 360 μmol/L) vs poorly-controlled ( n = 35; blood Phe > 360 μmol/L) PKU patients; both groups were significantly lower than non-PKU controls. Additionally, higher levels of homocysteine and increased mean platelet volume levels were also observed in PKU patients vs healthy controls and differences in these parameters were more evident in poorly-controlled PKU patients [20].…”

Section: Discussionmentioning

confidence: 99%

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

Trefz

Muntau

Kohlscheen³

et al. 2019

Orphanet J Rare Dis

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Trefz

Muntau

Kohlscheen³

et al. 2019

Orphanet J Rare Dis

View full text Add to dashboard Cite

show abstract

“…In other pathologic conditions, ECM/BCM ratio has positively correlated with risk of death in dialysis patients [19] , while PA has been negatively affected by nutritional imbalances, thus used as a prognostic factor in patients with homocystinuria [20] and cancer [21] . Both ECM/BCM ratio and PA values have been related to increased inflammation [17] , [18] , [19] , [21] , which are seen in several pathological processes including in PKU patients [37] , [38] . Because nutritional imbalances have shown to underlie increased inflammation [23] , [24] , the Phe-restricted diet could represent a threat to the overall health of patients.…”

Section: Discussionmentioning

confidence: 99%

Analysis of body composition and nutritional status in Brazilian phenylketonuria patients

Mazzola

Nalin

Castro

et al. 2016

Molecular Genetics and Metabolism Reports

View full text Add to dashboard Cite

BackgroundPhenylketonuria (PKU) is characterized by phenylalanine (Phe) accumulation to toxic levels due to the low activity of phenylalanine-hydroxylase. PKU patients must follow a Phe-restricted diet, which may put them in risk of nutritional disturbances. Therefore, we aimed to characterize body composition parameters and nutritional status in Brazilian PKU patients also considering their metabolic control.MethodsTwenty-seven treated PKU patients older than 5 years, and 27 age- and gender-matched controls, were analyzed for anthropometric features and body composition by bioelectrical impedance (BIA). Patients' metabolic control was assessed by historical Phe levels.ResultsThere was no effect of PKU type, time of diagnosis, or metabolic control for any analyzed parameter. About 75% of patients and controls were eutrophic, according to their BMI values. There were no difference between groups regarding body composition and other BIA-derived parameters.ConclusionsBrazilian PKU patients do not show differences in body composition and nutritional status in comparison with controls, regardless metabolic control. Although similar to controls, PKU patients may be in risk of disturbed nutritional and metabolic markers as seen for the general population.

show abstract

“…In the meta-analysis for folic acid the excessively high heterogeneity across the studies undermined its reliability to draw a conclusion on between group differences in status. Nonetheless 6 of the 7 studies [ 84 – 89 ] had confidence intervals on the right side of the plot (Fig. 6 ), suggesting positive differences between PKU patients and healthy controls.…”

Section: Discussionmentioning

confidence: 99%

Status of nutrients important in brain function in phenylketonuria: a systematic review and meta-analysis

Montoya

Singh

Cetinyurek-Yavuz

et al. 2018

Orphanet J Rare Dis

View full text Add to dashboard Cite

BackgroundDespite early and ongoing dietary management with a phe-restricted diet, suboptimal neuropsychological function has been observed in PKU. The restrictive nature of the PKU diet may expose patients to sub-optimal nutritional intake and deficiencies which may impact normal brain function. A systematic review of the published literature was carried out, where possible with meta-analysis, to compare the status of nutrients (Nutrients: DHA, EPA phospholipids, selenium, vitamins B6, B12, E, C, A, D, folic acid, choline, uridine, calcium, magnesium, zinc, iron, iodine and cholesterol) known to be important for brain development and functioning between individuals with PKU and healthy controls.ResultsOf 1534 publications identified, 65 studies met the entry criteria. Significantly lower levels of DHA, EPA and cholesterol were found for PKU patients compared to healthy controls. No significant differences in zinc, vitamins B12, E and D, calcium, iron and magnesium were found between PKU patients and controls. Because of considerable heterogeneity, the meta-analyses findings for folate and selenium were not reported. Due to an insufficient number of publications (< 4) no meta-analysis was undertaken for vitamins A, C and B6, choline, uridine, iodine and phospholipids.ConclusionsThe current data show that PKU patients have lower availability of DHA, EPA and cholesterol. Compliance with the phe-restricted diet including the micronutrient fortified protein substitute (PS) is essential to ensure adequate micronutrient status. Given the complexity of the diet, patients’ micronutrient and fatty acid status should be continuously monitored, with a particular focus on patients who are non-compliant or poorly compliant with their PS. Given their key role in brain function, assessment of the status of nutrients where limited data was found (e.g. choline, iodine) should be undertaken. Standardised reporting of studies in PKU would strengthen the output of meta-analysis and so better inform best practice for this rare condition.Electronic supplementary materialThe online version of this article (10.1186/s13023-018-0839-x) contains supplementary material, which is available to authorized users.

show abstract

Comparison of atherogenic risk factors among poorly controlled and well-controlled adolescent phenylketonuria patients

Cited by 12 publications

References 60 publications

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

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

Analysis of body composition and nutritional status in Brazilian phenylketonuria patients

Status of nutrients important in brain function in phenylketonuria: a systematic review and meta-analysis

Contact Info

Product

Resources

About