Phenylketonuria: nutritional advances and challenges

Abstract

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.

A Systematic Review of BH4 (Sapropterin) for the Adjuvant Treatment of Phenylketonuria

“…While advances in dietary management are improving outcomes for individuals with PKU, management of PKU can be difficult and onerous, leading to interest in identifying new ways of managing this lifelong condition. (Demirkol et al 2011;Harding and Blau 2010;Blau et al 2010;Giovannini et al 2012) In 2007, the United States Food and Drug Administration (FDA) approved sapropterin dihydrochloride (Kuvan®, formerly known as Phenoptin), the first pharmacologic treatment for PKU, under the stipulation that additional studies be conducted on efficacy and long-term safety. The goal of treatment with sapropterin dihydrochloride (hereafter, BH4) is to control blood Phe concentrations.…”

Molecular Nutrition Research—The Modern Way Of Performing Nutritional Science

“…In PKU the enzyme is absent, and too much phenylalanine accumulates in the body causing mental retardation. However, when newborns are diagnosed with PKU they can get a phenylalanine-free diet, which prevents the neurotoxic effects of high blood levels of phenylalanine [54]. The FTO (fat mass and obesity associated) gene is a good example on how variation in gene sequence interacts with environmental factors to determine phenotype, because carriers of one or more “risk” alleles have a 1.5 kg higher body weight per allele [55,56].…”

A fast high performance liquid chromatographic (HPLC) analysis of amino acid phenylketonuria disorder in dried blood spots and serum samples, employing C18 monolithic silica columns and photo diode array detection

“…3,4 Association of Phe in blood causes profound intellectual disability, neurological problems, eczematous rash, autism, seizures 3 and also mineral bone disease. [7][8][9][10][11][12] Due to the above-mentioned reasons; it is vital to simultaneously determine Phe and Tyr in physiological fluidics of neonatal and screen them in order to regularly monitor and control the disorder. have been investigated.…”