Intake Modalities of Amino Acid Supplements: A Real-World Data Collection from Phenylketonuria Patients.

BACKGROUND: To achieve a normal nutritional status, patients suffering from phenylketonuria (PKU) are typically prescribed amino acid (AA) supplements with low or no phenylalanine (Phe) content. Studies evaluating patient preferences regarding the intake modalities of AA supplements are limited. This study aimed to collect real-world data regarding prescription adherence and intake modalities of AA supplements reported by PKU patients while monitoring metabolic control. METHODS: This cross-sectional study included 33 PKU patients (16 female and 17 male) with a mean age of 27.2 years. Questionnaires were provided to assess information on AA supplement intake, such as prescription adherence rate, frequency and timing of administration, supplement formulation, and combination with food or drinks. Plasma phenylalanine levels were monitored during the study period. RESULTS: 51.5% (n = 17) of patients reported to lay within an adherence range of 75-100%. The majority of patients consumed AA supplements twice daily, with breakfast (87.9%) and afternoon snacks (51.5%). Powder supplements were most commonly used (72.7%) and often combined with milk and/or fruit juices (45.4%). CONCLUSIONS: Despite the known concerns related to treatment compliance among PKU adolescents and adults, most of the study participants reported a high level of adherence to AA supplement prescription. The personalized dietary regimens followed by the patients included in the current study represent a treatment approach that might be worth trying in non-compliant patients.

Micronutrient Deficiency in Inherited Metabolic Disorders Requiring Diet Regimen: A Brief Critical Review.

Many inherited metabolic disorders (IMDs), including disorders of amino acid, fatty acid, and carbohydrate metabolism, are treated with a dietary reduction or exclusion of certain macronutrients, putting one at risk of a reduced intake of micronutrients. In this review, we aim to provide available evidence on the most common micronutrient deficits related to specific dietary approaches and on the management of their deficiency, in the meanwhile discussing the main critical points of each nutritional supplementation. The emerging concepts are that a great heterogeneity in clinical practice exists, as well as no univocal evidence on the most common micronutrient abnormalities. In phenylketonuria, for example, micronutrients are recommended to be supplemented through protein substitutes; however, not all formulas are equally supplemented and some of them are not added with micronutrients. Data on pyridoxine and riboflavin status in these patients are particularly scarce. In long-chain fatty acid oxidation disorders, no specific recommendations on micronutrient supplementation are available. Regarding carbohydrate metabolism disorders, the difficult-to-ascertain sugar content in supplementation formulas is still a matter of concern. A ketogenic diet may predispose one to both oligoelement deficits and their overload, and therefore deserves specific formulations. In conclusion, our overview points out the lack of unanimous approaches to micronutrient deficiencies, the need for specific formulations for IMDs, and the necessity of high-quality studies, particularly for some under-investigated deficits.

Combined isobutyryl-CoA and multiple acyl-CoA dehydrogenase deficiency in a boy with altered riboflavin homeostasis.

In this report, we describe the case of an 11-year-old boy, who came to our attention for myalgia and muscle weakness, associated with inappetence and vomiting. Hypertransaminasemia was also noted, with ultrasound evidence of hepatomegaly. Biochemical investigations revealed acylcarnitine and organic acid profiles resembling those seen in MADD, that is, multiple acyl-CoA dehydrogenase deficiencies (OMIM #231680) a rare inherited disorder of fatty acids, amino acids, and choline metabolism. The patient carried a single pathogenetic variant in the ETFDH gene (c.524G>A, p.Arg175His) and no pathogenetic variant in the riboflavin (Rf) homeostasis related genes (SLC52A1, SLC52A2, SLC52A3, SLC25A32, FLAD1). Instead, compound heterozygosity was found in the ACAD8 gene (c.512C>G, p.Ser171Cys; c.822C>A, p.Asn274Lys), coding for isobutyryl-CoA dehydrogenase (IBD), whose pathogenic variants are associated to IBD deficiency (OMIM #611283), a rare autosomal recessive disorder of valine catabolism. The c.822C>A was never previously described in a patient. Subsequent further analyses of Rf homeostasis showed reduced levels of flavins in plasma and altered FAD-dependent enzymatic activities in erythrocytes, as well as a significant reduction in the level of the plasma membrane Rf transporter 2 in erythrocytes. The observed Rf/flavin scarcity in this patient, possibly associated with a decreased ETF:QO efficiency might be responsible for the observed MADD-like phenotype. The patient's clinical picture improved after supplementation of Rf, l-carnitine, Coenzyme Q10, and also 3OH-butyrate. This report demonstrates that, even in the absence of genetic defects in genes involved in Rf homeostasis, further targeted molecular analysis may reveal secondary and possibly treatable biochemical alterations in this pattern.

Is sunlight enough for sufficient vitamin D status in children and adolescents? A survey in a sunny region of southern Italy.

OBJECTIVES: Because it is involved in calcium homeostasis, vitamin D is a prohormone with many implications for health, especially bone health. Hypovitaminosis D is considered pandemic worldwide, with important health health consequences. The aim of our study was to evaluate vitamin D levels in children living in a southern region of Italy with high exposure to sunlight for at least 5 mo a year along with contributing factors. METHODS: A total of 1484 children and adolescents (age 0.02-17.74 y) living in the Apulia region (Southern Italy) were studied. Serum 25-hydroxyvitamin D (25[OH]D) concentrations were assessed and vitamin status defined as follows: deficiency with serum 25(OH)D < 20 ng/mL, insufficiency from 20 to 29.9 ng/mL, and sufficiency with serum 25(OH)D from 30 to 100 ng/mL. RESULTS: The median serum 25(OH)D levels were 20.2 ng/mL (interquartile range, 14.5-26.4 ng/mL): 48.9% of the overall population had 25(OH)D < 20 ng/mL and only 15% had sufficient 25(OH)D values. There was an inverse association between blood levels of 25(OH)D and age (P < 0.001, ρ: -0.113). Significant 25(OH)D variations were recorded according to the season in which blood samples were drawn, but even during summer only 32.6% of analyzed children had sufficient 25(OH)D levels. CONCLUSIONS: More than 80% of our population had 25(OH)D less than sufficiency cutoff levels. Results highlight a high prevalence of 25(OH)D deficiency in our area, even during summer. It is important to establish screening, supplementation guidelines, and pediatric cutoff levels to optimize vitamin D status in children, taking into account age, nutritional status, and seasonality.