Breastfeeding in Phenylketonuria: Changing Modalities, Changing Perspectives.

Phenylketonuria (PKU) management aims to control phenylalanine (Phe) intakes. In newborns and infants this implies possible titration of Human milk (HM) with supplementation of Phe-free formula. HM benefits, better if prolonged, are well known in healthy populations, suggesting it may be used in PKU patients. Despite that, the current literature does not define recommendations on how best perform it in such a population. The main purpose of this study was to evaluate nutrition approaches in newborns and infants affected by PKU and to define if differences can influence the duration of breastfeeding. Data from 42 PKU infants were reviewed. Of these, 67% were breastfed with the use of three different approaches. The type of approach used impacted the duration of breastfeeding, which was longer when using a pre-measured amount of Phe-free formula administered prior to HM. This is the first study to suggest a specific method for breastfeeding in PKU. Considering widely known breastfeeding benefits, both for patients and their mothers, our data should encourage adequate awareness on how to choose correct breastfeeding modalities.

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.

Determinants of Plasma Docosahexaenoic Acid Levels and Their Relationship to Neurological and Cognitive Functions in PKU Patients: A Double Blind Randomized Supplementation Study.

Children with phenylketonuria (PKU) follow a protein restricted diet with negligible amounts of docosahexaenoic acid (DHA). Low DHA intakes might explain subtle neurological deficits in PKU. We studied whether a DHA supply modified plasma DHA and neurological and intellectual functioning in PKU. In a double-blind multicentric trial, 109 PKU patients were randomized to DHA doses from 0 to 7 mg/kg&day for six months. Before and after supplementation, we determined plasma fatty acid concentrations, latencies of visually evoked potentials, fine and gross motor behavior, and IQ. Fatty acid desaturase genotypes were also determined. DHA supplementation increased plasma glycerophospholipid DHA proportional to dose by 0.4% DHA per 1 mg intake/kg bodyweight. Functional outcomes were not associated with DHA status before and after intervention and remained unchanged by supplementation. Genotypes were associated with plasma arachidonic acid levels and, if considered together with the levels of the precursor alpha-linolenic acid, also with DHA. Functional outcomes and supplementation effects were not significantly associated with genotype. DHA intakes up to 7 mg/kg did not improve neurological functions in PKU children. Nervous tissues may be less prone to low DHA levels after infancy, or higher doses might be required to impact neurological functions. In situations of minimal dietary DHA, endogenous synthesis of DHA from alpha-linolenic acid could relevantly contribute to DHA status.

Exploring Drivers of Liking of Low-Phenylalanine Products in Subjects with Phenyilketonuria Using Check-All-That-Apply Method.

The aim of the present study was to apply the Check-all-that-apply (CATA) method in an ambulatory context involving subjects with phenylketonuria (PKU) to obtain a sensory description and to find the drivers of liking of low-phenylalanine products (Glycomacropeptide vs. L-amino acids formulas). 86 subjects with PKU (age range: 8⁻55 years) evaluated 8 samples: 4 L-amino acid formulas and 4 Glycomacropeptide (GMP) formulas, flavored with neutral, chocolate, strawberry and tomato aromas. Participants were asked to indicate which sensory attributes characterized each formulations and to score the overall liking. Significant differences were found regarding liking scores (F = 65.29; p < 0.001). GMP samples flavored with chocolate and strawberry, described as sweets, with a mild and natural taste and odor, were the most appreciated. Overall, GMP formulas obtained higher liking scores compared to L-amino acid formulas. Tomato flavored samples, described as bitter, salty, with artificial color, with strong taste and odor, obtained the lowest scores. In conclusion, CATA questionnaire seems to be a suitable method also in ambulatory context since this approach suggested that different foods and beverages with GMP could be developed to improve dietary treatment compliance of subjects with PKU from school age onwards.

Vitamin E Improves Clinical Outcome of Patients Affected by Glycogen Storage Disease Type Ib.

BACKGROUND: It has been suggested, on a few GSD1b patients, that vitamin E improves neutrophil count and reduces frequency and severity of infections.The main objective of the present study was to investigate the efficacy of vitamin E on the neutropenia, neutrophil dysfunction and IBD in the entire Italian caseload of GSD1b patients. PATIENTS AND METHODS: Eighteen GSD1b patients, median age at the time of the study protocol 14.5 (range, 0.6-42 years), were enrolled from four Italian referral centres for metabolic diseases. For the evaluation of the efficacy of vitamin E, neutrophil count and function, frequency of infections needing hospitalization and inflammatory bowel activity were evaluated periodically all over one year before and during vitamin E therapy. RESULTS: Frequency (1.5 ± 0.1 vs. 6.0 ± 0.6, p = 0.003) and severity of infections (2.2 ± 0.2 vs. 3.7 ± 0.4, p = 0.003) were lower and mean value of neutrophil count (1,583 ± 668 vs. 941 ± 809, p = 0.03) higher during vitamin E supplementation. Neutrophil function results improved during vitamin supplementation. PCDAI showed a significant reduction in the inflammatory activity during vitamin E supplementation (9 ± 1.4 vs. 13 ± 1.2, p = 0.006). In seven patients G-CSF requirement decreased and the dose was reduced after the end of the study.In conclusion, our study demonstrated the efficacy of vitamin E supplementation. Vitamin E has evident advantages as compared to G-CSF, as it can be assumed orally, and it has not been associated with severe side effects.

Phenylketonuria: nutritional advances and challenges.

Despite the appearance of new treatment, dietary approach remains the mainstay of PKU therapy. The nutritional management has become complex to optimize PKU patients' growth, development and diet compliance. This paper review critically new advances and challenges that have recently focused attention on potential relevant of LCPUFA supplementation, progress in protein substitutes and new protein sources, large neutral amino acids and sapropterin. Given the functional effects, DHA is conditionally essential substrates that should be supplied with PKU diet in infancy but even beyond. An European Commission Programme is going on to establish quantitative DHA requirements in this population. Improvements in the palatability, presentation, convenience and nutritional composition of protein substitutes have helped to improve long-term compliance with PKU diet, although it can be expected for further improvement in this area. Glycomacropeptide, a new protein source, may help to support dietary compliance of PKU subject but further studies are needed to evaluate this metabolic and nutritional issues. The PKU diet is difficult to maintain in adolescence and adult life. Treatment with large neutral amino acids or sapropterin in selected cases can be helpful. However, more studies are necessary to investigate the potential role, dose, and composition of large neutral amino acids in PKU treatment and to show long-term efficacy and tolerance. Ideally treatment with sapropterin would lead to acceptable blood Phe control without dietary treatment but this is uncommon and sapropterin will usually be given in combination with dietary treatment, but clinical protocol evaluating adjustment of PKU diet and sapropterin dosage are needed.In conclusion PKU diet and the new existing treatments, that need to be optimized, may be a complete and combined strategy possibly positive impacting on the psychological, social, and neurocognitive life of PKU patients.