Psychosocial functioning in children with phenylketonuria: relationships between quality of life and parenting indicators

This study aimed to assess the impact of phenylketonuria (PKU) and its treatment on parent and child health-related quality of life (HRQoL), and to identify the parenting-related correlates of parent and child HRQoL, as well as metabolic control.Eighteen mothers of 2 to 12-year-old children with PKU participated and completed a series of self-report questionnaires including the Phenylketonuria Impact and Treatment Quality of Life Questionnaire (PKU-QOL).Mothers reported that the most significant impact of PKU on HRQoL was in relation to impact of their child's anxiety during blood tests on their own HRQoL, and guilt related to poor adherence to dietary restrictions and supplementation regimens. Higher reported intensity of child emotional and behavioural difficulties and parenting stress were associated with higher scores for PKU symptoms on the PKU-QOL, higher scores for emotional, social and overall impact of PKU, and higher scores for impact of dietary restriction. Where mothers reported greater use of overreactivity as a parenting strategy, children tended to have better lifetime phenylalanine (Phe) levels; however, the overall impact of PKU and the impact of supplement administration on mothers' HRQoL was worse for these families.These findings have implications for a holistic family-centred approach to the care of children with PKU and their families

Clinician experience, perceptions, and acceptance of paediatric complex care nurse practitioner roles

Background: Nurse practitioner (NP) roles are implemented to increase access to care in response to rising demands and pressures in the health system, yet little evaluation is undertaken to assess how these new roles integrate with services. Aim: To identify health professionals’ experiences, perceptions, and acceptance of NP roles in complex care medical subspecialties within a paediatric tertiary hospital and health services. Methods: The AUSPRAC validated survey was distributed in both electronic and paper forms to a purposeful cohort of multidisciplinary health professionals (n = 208) working directly or collaboratively with both established NPs and novice/in training NPs. Nine medical subspecialties were represented including metabolic, immunisation and oncology. Two reminders were sent to non-responders. All NP roles within nine medical specialties were evaluated. Data were tabulated and descriptively analysed. Findings: Ninety-two responses were received (response rate 44%). Services with highest representation were Immunisation (71%), Metabolic Medicine and Palliative Care (45%) each. Responses were received from medical (42%) nursing (30%) and other healthcare providers (27%) including allied health clinicians. Most respondents agreed they understood NP roles (89%), agreed their introduction into the service had been a success (85%) and that NP services met the needs of the patients (91%). Some (9%) respondents reported they feared NP prescribing increased the risk of incorrect treatment with 7% not trusting NPs to diagnose correctly and some (15%) worried that NPs did not have the necessary knowledge to prescribe. Free text comments were generally positive and supportive of the roles, with few negative statements. Discussion: While most NP roles were positively viewed, breakdowns in communication processes affected understanding and acceptance of some NP roles. Clearly defining the scope, purpose and benefits of NP roles should be communicated to individual teams and across whole organisations. Conclusion: NP roles are largely well accepted within this paediatric tertiary service, which demonstrates a shift in culture from research undertaken at the turn of the century. Attention to implementation factors may improve successful integration of new roles into services.</p

Expert Consensus on the Long-Term Effectiveness of Medical Nutrition Therapy and Its Impact on the Outcomes of Adults with Phenylketonuria

Many adults with phenylketonuria (PKU) rely on medical nutrition therapy (MNT; low phenylalanine (Phe) diet with protein substitutes/medical foods) to maintain blood Phe concentrations within recommended ranges and prevent PKU-associated comorbidities. Despite disease detection through newborn screening and introduction of MNT as early as birth, adherence to MNT often deteriorates from childhood onwards, complicating the assessment of its effectiveness in the long term. Via a modified Delphi process, consensus (≥70% agreement) was sought on 19 statements among an international, multidisciplinary 13-member expert panel. After three iterative voting rounds, the panel achieved consensus on 17 statements related to the limitations of the long-term effectiveness of MNT (7), the burden of long-term reliance on MNT (4), and its potential long-term detrimental health effects (6). According to the expert panel, the effectiveness of MNT is limited in the long term, is associated with a high treatment burden, and demonstrates that adults with PKU are often unable to achieve metabolic control through dietary management alone, creating an unmet need in the adult PKU population

Squalene synthase deficiency: clinical, biochemical, and molecular characterization of a defect in cholesterol biosynthesis

Mendelian disorders of cholesterol biosynthesis typically result in multi-system clinical phenotypes, underlining the importance of\ua0cholesterol in embryogenesis and development. FDFT1 encodes for an evolutionarily conserved enzyme, squalene synthase (SS, farnesyl-pyrophosphate farnesyl-transferase 1), which catalyzes the first committed step in cholesterol biosynthesis. We report three individuals with profound developmental delay, brain abnormalities, 2-3 syndactyly of the toes, and facial dysmorphisms, resembling Smith-Lemli-Opitz syndrome, the most common cholesterol biogenesis defect. The metabolite profile in plasma and\ua0urine suggested that their defect was at the level of squalene synthase. Whole-exome sequencing was used to identify recessive disease-causing variants in FDFT1. Functional characterization of one variant demonstrated a partial splicing defect and altered promoter and/or enhancer activity, reflecting essential mechanisms for regulating cholesterol biosynthesis/uptake in steady\ua0state

An international classification of inherited metabolic disorders (ICIMD)

Several initiatives at establishing a classification of inherited metabolic disorders have been published previously, some focusing on pathomechanisms, others on clinical manifestations, while yet another attempted a simplified approach of a comprehensive nosology. Some of these classifications suffered from shortcomings, such as lack of a mechanism for continuous update in light of a rapidly evolving field, or lack of widespread input from the metabolic community at large. Our classification-the International Classification of Inherited Metabolic Disorders, or International Classification of Inborn Metabolic Disorders (ICIMD)-includes 1450 disorders, and differs from prior approaches in that it benefited from input by a large number of experts in the field, and was endorsed by major metabolic societies around the globe. Several criteria such as pathway involvement and pathomechanisms were considered. The main purpose of the hierarchical, group-based approach of the ICIMD is an improved understanding of the interconnections between many individual conditions that may share functional, clinical, and diagnostic features. The ICIMD aims to include any primary genetic condition in which alteration of a biochemical pathway is intrinsic to specific biochemical, clinical, and/or pathophysiological features. As new disorders are discovered, we will seek the opinion of experts in the advisory board prior to inclusion in the appropriate group of the ICIMD, thus guaranteeing the continuing relevance of this classification via regular curation and expert advice