Parents' Perceptions Regarding Their Children's Medications and Expert-Assessed Drug-Related Problems in Pediatric Patients with Inborn Errors of Metabolism.

We aimed to explore parents' perceptions of their children's medication use for inborn errors of metabolism (IEM), including the importance of medication intake, potential complications, and concerns about adverse drug reactions (ADR). Additionally, we aimed to determine expert-assessed clinically relevant drug-related problems, particularly those attributable to IEM. We interviewed 108 parents of 119 pediatric patients with IEM using a questionnaire relating to their perceptions regarding their children's IEM medication. In affected siblings, a questionnaire was used for each child. We performed medication analyses to evaluate the patient's complete medication regimen for clinically relevant drug-related problems, including medication for conditions other than IEM. It was very important to the parents of 85% of the patients to use IEM medication exactly as prescribed. The parents of 41% of patients perceived complications in their children's use of IEM medication. The parents of 47% of patients reported fears concerning ADR because of IEM medication. Parents observed ADR in 27% of patients because of IEM medication. In 44% of patients, medication for conditions other than IEM was inadequate because of drug-related problems not associated with the IEM; a safe alternative existed in 21% of patients. In summary, almost half of the parents of patients with IEM reported complications with their child's IEM medication intake and fears of ADR. Medication analyses showed that drug-related problems occurred regardless of IEM, emphasizing the general need to prescribe and dispense adequate, child-appropriate medication to minimize clinically relevant drug-related problems in pediatric patients.

Preventing maternal phenylketonuria (PKU) syndrome: important factors to achieve good metabolic control throughout pregnancy.

BACKGROUND: Insufficient metabolic control during pregnancy of mothers with phenylketonuria (PKU) leads to maternal PKU syndrome, a severe embryo-/fetopathy. Since maintaining or reintroducing the strict phenylalanine (Phe) limited diet in adults with PKU is challenging, we evaluated the most important dietary and psychosocial factors to gain and sustain good metabolic control in phenylketonuric women throughout pregnancy by a questionnaire survey with 38 questions concerning therapy feasibility. Among them, the key questions covered 5 essential items of PKU care as follows: General information about maternal PKU, PKU training, diet implementation, individual metabolic care, personal support. In addition, all participating PKU mothers were asked to estimate the quality of their personal metabolic control of the concluded pregnancies. 54 PKU mothers with 81 pregnancies were approached at 12 metabolic centers in Germany and Austria were included. According to metabolic control, pregnancies of PKU women were divided in two groups: group "ideal" (not more than 5% of all blood Phe concentrations during pregnancy > 360 µmol/l; n = 23) and group "suboptimal" (all others; n = 51). RESULTS: The demand for support was equally distributed among groups, concerning both amount and content. Personal support by the direct social environment (partner, family and friends) ("suboptimal" 71% vs "ideal" 78%) as well as individual metabolic care by the specialized metabolic center (both groups around 60%) were rated as most important factors. The groups differed significantly with respect to the estimation of the quality of their metabolic situation (p < 0.001). Group "ideal" presented a 100% realistic self-assessment. In contrast, group "suboptimal" overestimated their metabolic control in 53% of the pregnancies. Offspring of group "suboptimal" showed clinical signs of maternal PKU-syndrome in 27%. CONCLUSION: The development of training programs by specialized metabolic centers for females with PKU in child bearing age is crucial, especially since those mothers at risk of giving birth to a child with maternal PKU syndrome are not aware of their suboptimal metabolic control. Such programs should provide specific awareness training for the own metabolic situation and should include partners and families.

Psychological well-being of early and continuously treated phenylketonuria patients.

BACKGROUND: Despite enormous advances in therapy, phenylketonuria (PKU) remains an incurable, inherited metabolic disease requiring life-long treatment with potential to negatively impact quality of life and psychological well-being. Therefore, the aim of this study was to screen early diagnosed and continuously treated children with PKU on psychological strengths and behavioral difficulties. METHODS: Evaluation of psychological strengths and behavioral difficulties in 49 patients with PKU (23f, 2-17 years) by Strengths and Difficulties Questionnaire (SDQ; self-report 11-17 years and parent-report 2-17 years). Comparison to age, sex and BMI-matched healthy controls (n = 98; 46f). RESULTS: In patients with PKU and healthy controls median SDQ Total Difficulties Score and median scores of subscales were within the normal range in parent- and self-report, irrespective of sex and age group (children 2-10 years, adolescents 11-17 years). No influence of long-term metabolic control in PKU on SDQ could be revealed. The 2- to 10-year-old boys with PKU showed significantly higher scores in Prosocial Behavior compared to their healthy peers (P = .032). Likewise, adolescent boys with PKU showed fewer Conduct Problems (parent-report, P = .006). Adolescent girls with PKU rated themselves more often as abnormal in the subscale Emotional Problems compared to their healthy peers (P = .041). This subscale was also responsible for a significantly different Total SDQ Difficulties Score between patients and their parents' report (P = .008). DISCUSSION: SDQ represents a suitable instrument within the care for patients with PKU. Specific aspects, however, require separate consideration and evaluation with respect to this chronic disease. Special attention should be paid on adolescent PKU girls who seem to be at risk to develop emotional problem.

Ten years of specialized adult care for phenylketonuria - a single-centre experience.

BACKGROUND: Specialized adult care of phenylketonuria (PKU) patients is of increasing importance. Adult outpatient clinics for inherited errors of metabolism can help to achieve this task, but experience is limited. Ten years after establishment of a coordinated transition process and specialised adult care for inherited metabolic diseases, adult PKU care was evaluated with respect to metabolic control, therapy satisfaction, life satisfaction, sociodemographic data, economical welfare as well as pregnancy outcome. METHODS: All PKU patients transferred from paediatric to adult care between 2005 and 2015 were identified. A retrospective data analysis and a cross-sectional survey in a sub-cohort of 30 patients including a questionnaire for assessing quality of life (FLZm) were performed as a single-centre investigation at the metabolic department of the University Hospital Leipzig, Germany. For statistical analysis, Mann-Whitney-U-test, t-test for independent samples, ANOVA and chi square test were used as appropriate. RESULTS: 96 PKU patients (56 females/40 males; median age 32 years, range 18-62) were included. In the last 3-year period, 81% of the transferred patients still kept contact to the adult care centre. Metabolic control was stable over the evaluation period and dried blood phenylalanine concentrations mostly remained within the therapeutic range (median 673.0 µmol/l, range 213.0-1381.1). Sociodemographic data, economical welfare and life satisfaction data were comparable to data from the general population. However, differences could be revealed when splitting the cohort according to time of diagnosis and to management during childhood. 83% of the PKU adults were satisfied with the transition process and current adult care. 25 completed pregnancies were supervised; three newborns, born after unplanned pregnancy, showed characteristic symptoms of maternal PKU syndrome. CONCLUSIONS: Continuous care for adult PKU patients in a specialized outpatient clinic is successful, leading to good to satisfactory metabolic control and social outcomes. Uninterrupted good metabolic treatment throughout childhood and adolescence positively influences educational, professional and economic success in later life. Further effort in specialized paediatric and adult metabolic care is needed to prevent loss of follow-up and to support the recommended life-long treatment and/or care.

Effect of dietary regime on metabolic control in phenylketonuria: Is exact calculation of phenylalanine intake really necessary?

BACKGROUND: A phenylalanine (Phe) restricted dietary management is required in phenylketonuria (PKU) to maintain good metabolic control. Nevertheless, five different models of dietary regimes, which differ in their accuracy of Phe documentation, are used. To investigate the effect of the dietary regime on metabolic control, a multicenter evaluation was performed. PATIENTS/METHODS: 149 patients (max. 800 mg Phe-intake/day; 108 children aged 1-9 years and 41 adolescents aged 10-15 years) could be included. They were separated according to age and dietary regime, revealed by a questionnaire on dietary habits. Dietary regimes vary from daily strict calculation of all Phe-intake (group 1) to a rather loose regime only estimating Phe-intake and including high protein food (group 5). Data were analyzed with respect to metabolic control (Phe-concentrations, Phe-concentrations above upper recommended limit during 6 months before the interview), Phe-intake (mg/day) and age (years). RESULTS: Median Phe-concentrations in children did not differ significantly among diet groups (group 1: 161; 2: 229, 3: 236, 4: 249, 5: 288 µmol/l, p = 0.175). However, exact daily Phe calculation led to significantly lower percentage of Phe concentrations above the upper recommended limit (group 1: 17, 2: 50, 3: 42, 4: 50, 5: 75%, p = 0.035). All included patients showed good to acceptable metabolic control. Patients on the dietary regime with the least accuracy, consuming also high protein foods, showed the poorest metabolic control. Median Phe concentrations of all other groups remained within recommended ranges, including from groups not calculating special low protein foods, fruit and vegetables and using a simplified system of recording Phe-intake. In adolescents no significant differences among diet groups were revealed. CONCLUSION: Exact calculation of Phe content of all food is not necessary to achieve good metabolic control in children and adolescents with PKU. Excluding special low protein food, as well as fruit and vegetables from calculation of Phe-intake has no impact on metabolic control. However including protein rich food into the diet and simply estimating all Phe-intake appears insufficient. The simplification of dietary regime may be helpful in enhancing acceptability and feasibility.