Low bone mineralization in phenylketonuria may be due to undiagnosed metabolic acidosis.

Background: Dietary intervention is to date the mainstay treatment to prevent toxic phenylalanine (Phe) accumulation in PKU patients. Despite success preventing central nervous system damage, there is increasing evidence of possible other unfavorable outcomes affecting other systems, e.g. kidney and bone; underlying mechanisms are yet to be fully elucidated. Methods: This observational, cross-sectional and descriptive study investigated 20 adult with PKU evaluating biochemical parameters, BMD measurements and extrapolating data from 3-days food records and protein substitutes (PS) and special low protein foods (SLPF) composition. Results: Blood gas venous analysis (VBG) indices were indicative of metabolic acidosis in 60% of PKU patients and VBG pH significantly correlated with BMD's Z-score (p-value = 0.022) even if its overall mean was in range (-1.29). Low bone mineral density for chronological age (Z-score < - 2.0) was found in 4 patients (20%). Indices of kidney function were not impaired. All used PS had a moderate excess of acidity, while SLPF were alkalizing and type/variety of consumed vegetables did not determine significant changes in acid-base equilibrium. Total intakes of potassium and magnesium were lower than expected. Discussion: PKU patients seem to be at risk of metabolic acidosis, directly linked to possible low bone mineralization. This may be related to the acidic composition of PS, potentially capable of acidifying the entire diet. Reported low intakes of potassium and magnesium may be relevant to these observations. Further studies are needed to better address these topics.

L-alanine supplementation in Pompe disease (IOPD): a potential therapeutic implementation for patients on ERT? A case report.

BACKGROUND: Pompe disease (PD) is a disorder of glycogen metabolism conditioning a progressive and life conditioning myopathy. Enzyme replacement therapy (ERT) is currently the best treatment option for PD, but is not resolutive. While other potential therapeutic approaches have been reported before, these have never been tried as co- treatments. L-alanine oral supplementation (LAOS) has been proven to reduce muscle breakdown: we hereby report the first case of supplementation on a PD patient on ERT. CASE PRESENTATION: F. is a 9 y.o. infantile onset Pompe Disease (IOPD) girl ERT-treated since age 1 developing a progressive myopathy. We started her on LAOS and performed assessments at baseline, 6 and 9 months. At baseline, F.'s weight, height and BMI were within normal ranges, while body composition showed low fat mass -FM and high resting energy expenditure-REE levels. After LAOS, a progressive FM increase and REE reduction could be observed both at 6 and 9 months. CONCLUSIONS: ERT is not curative for PD patients thus additional treatments could be considered to improve outcomes. Our patient showed physical signs of inability to accumulate energy when exclusively on ERT, while FM increase and REE reduction occurred when supplemented with LAOS, likely reflecting anabolic pathways' implementation. This is the first case reporting potential LAOS benefits in PD-on ERT patients. Longitudinal case control studies are yet needed to evaluate possible efficacy of combined LAOS And ERT treatment in PD patients.

Parental Perception of Body Weight Status of Their 8-year-old Children: Findings from the European CHOP Study.

BACKGROUND: Maternal perception of child weight status in children with overweight or obesity has received a lot of attention but data on paternal perception of children from presumably healthy cohorts are lacking. OBJECTIVE: We aimed to investigate paternal and maternal perception of child weight status at the age of 8 years in a cohort of 591 children from 5 European countries. MATERIAL AND METHODS: Included were 8-year-old children and their parents participating in the European Childhood Obesity Project (EU CHOP). Weight and height of children and parents were measured and Body Mass Index (BMI, kg/m2) was calculated. Both parents were asked to assess their perception of child weight status using Eckstein scales and their concern about child overweight. The agreement between mother and father perceptions was assessed by Cohen kappa coefficient and their relationship was analyzed by linear mixed effects models based on ordinal logistic regression, accounting for country, child gender and BMI, parental BMI, level of education, concern and type of feeding during first year of life. RESULTS: Data from children and both parents were available for 432 girls and boys. Mean BMI was comparable in boys and girls (16.7 ± 2.31 vs. 16.9 ± 2.87 kg/m2, P = 0.55). In total, 172 children (29.3%) were overweight or obese. There was a high degree of agreement between mother and father perceptions of their child's weight status (Cohen kappa 0.77). Multivariate modelling showed that perception levels significantly increased with child BMI but were globally lower than assessed. They differed between countries, gender and types of feeding during first year of life, were influenced by education level of the father but were not related to parental BMI and concern about childhood overweight. CONCLUSIONS: The study showed no overall differences between mothers and fathers in rating their child's weight status but both parents had a propensity to underestimate their child's actual weight, particularly in boys. The EU CHOP trial registered at clinicaltrials.gov as NCT00338689.

PKU and COVID19: How the pandemic changed metabolic control.

BACKGROUND: COVID19 pandemic urged the need to take severe measures for reducing the epidemic spread. Lockdowns were imposed throughout countries and even Inborn errors of metabolism (IEMs) affected patients had to face it and adapt, with management strategies changes coming along. Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism causing, when not treated, blood Phe increases and consequent central nervous system (CNS) damage. Dietary intervention is the main recognized treatment and must be maintained long-life, however adherence is often suboptimal in adulthood. Aim of this study was to evaluate whether and how the pandemic had impacted PKUs metabolic control and what factors may have played a role as potential modifiers. METHODS: Patients ≥4 yo and in follow-up at our Metabolic Clinic were enrolled in this study, divided into subgroups according to age (GROUP A < 12 yo; GROUP B ≥ 12 yo). Videoconsults were conducted on a minimum monthly basis and collected DBS were studied and compared to previous year same time-period in order to evaluate possible changes. RESULTS: 39% of patients (n = 121) increased the number of performed DBS. "Non-compliant" patients were reduced (11-3%) with a - 14% of patients with mean Phe levels >600 umol/l and a - 8% of patients with 100% DBS above same level. GROUP A maintained substantially unchanged metabolic control among two analyzed time-periods. On the contrary, GROUP B demonstrated significant reductions in mean blood Phe concentrations (p < 0.0001) during the pandemic (mean 454 umol/l, SD ± 252, vs. 556.4 umol/l, SD ± 301). DISCUSSION: COVID19 pandemic strongly impacted people's life with lifestyle habits changing consistently. PKU patients had to adapt their dietary restrictions to the new environment they were exposed to and, if younger patients could have been less exposed (meals strictly according to diet plan independently from setting), adolescent and adults strongly reflected the obligation to stay home by showing better metabolic control. Multiple factors could have played a role in that and the availability of teleconsultancy may have contributed allowing easier connections, but our data demonstrate how the pandemic and the environment can strongly impact PKUs adherence to treatment and how removing distance barriers can ameliorate and optimize metabolic compliance.