Improved Eating Behaviour and Nutrient Intake in Noncompliant Patients with Phenylketonuria after Reintroducing a Protein Substitute: Observations from a Multicentre Study

Green, Ben; Rahman, Yusof; Firman, Sarah; Adam, Sarah; Jenkinson, Fiona; Nicol, Claire; Adams, Sandra; Dawson, Charlotte; Robertson, Louise; Dunlop, Carolyn; Cozens, Alison; Hubbard, G.P.; Stratton, Rebecca J.

doi:10.3390/nu11092035

Cited by 9 publications

(8 citation statements)

References 33 publications

(48 reference statements)

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“…The ability to conduct a research study is particularly difficult when the patients are predominantly noncompliant PKU and are disengaged from active metabolic follow-up, highlighting the challenges in their inclusion in relatively complicated research procedures. This has done recruitment particularly difficult and the design of a randomized control trial study complex, as recently reported by Green et al [38].…”

Section: Limitationsmentioning

confidence: 99%

Large Neutral Amino Acid Therapy Increases Tyrosine Levels in Adult Patients with Phenylketonuria: A Long-Term Study

Cazzorla¹,

Massa²,

Polo³

et al. 2019

Nutrients

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The standard treatment for phenylketonuria (PKU) is a lifelong low-phenylalanine (Phe) diet, supplemented with Phe-free protein substitutes; however, adult patients often show poor adherence to therapy. Alternative treatment options include the use of large neutral amino acids (LNAA). The aim of this study was to determine the Phe, tyrosine (Tyr), and Phe/Tyr ratio in a cohort of sub-optimally controlled adult patients with classical PKU treated with a new LNAA formulation. Twelve patients received a Phe-restricted diet plus a slow-release LNAA product taken three times per day, at a dose of 1 g/kg body weight (mean 0.8 ± 0.24 g/kg/day), over a 12-month period. The product is in a microgranulated formulation, which incorporates all amino acids and uses sodium alginate as a hydrophilic carrier to prolong its release. This LNAA formulation provides up to 80% of the total protein requirement, with the rest of the protein supplied by natural food. Patients had fortnightly measurements of Phe and Tyr levels over a 12-month period after the introduction of LNAA. All patients completed the 12-month treatment period. Overall, adherence to the new LNAA tablets was very good compared with a previous amino acid mixture, for which taste was a major complaint by patients. Phe levels remained unchanged (p = 0.0522), and Tyr levels increased (p = 0.0195). Consequently, the Phe/Tyr ratio decreased significantly (p < 0.05) in the majority of patients treated. In conclusion, LNAA treatment increases Tyr levels in sub-optimally controlled adult PKU patients, while offering the potential to improve their adherence to treatment.

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Section: Limitationsmentioning

confidence: 99%

Large Neutral Amino Acid Therapy Increases Tyrosine Levels in Adult Patients with Phenylketonuria: A Long-Term Study

Cazzorla¹,

Massa²,

Polo³

et al. 2019

Nutrients

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“…Compliance is critically related to patient knowledge on his/her condition, and to factors influencing motivation and attitude [ 7 , 32 ]. In this framework, it is crucial to implement a patient tailored approach to improve long-term adherence to diet treatment and prevent the nutritional, metabolic and cognitive abnormalities associated to non-compliance [ 6 , 32 , 35 ]. Accordingly, doctor-patient communication and relationship between patient and healthcare system should be seriously considered as a main factor facilitating adherence and engagement in the management of PKU, particularly during transition and in adults [ 5 , 7 , 10 ].…”

Section: Resultsmentioning

confidence: 99%

Italian national consensus statement on management and pharmacological treatment of phenylketonuria

Burlina

Biasucci

Carbone

et al. 2021

Orphanet J Rare Dis

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Background Phenylketonuria (PKU) is a rare inherited metabolic disorder caused by defects in the phenylalanine-hydroxylase gene (PAH), the enzyme catalyzing the conversion of phenylalanine to tyrosine. PAH impairment causes phenylalanine accumulation in the blood and brain, with a broad spectrum of pathophysiological and neurological consequences for patients. Prevalence of disease varies, with peaks in some regions and countries, including Italy. A recent expert survey described the real-life of clinical practice for PKU in Italy, revealing inhomogeneities in disease management, particularly concerning approach to pharmacotherapy with sapropterin hydrochloride, analogous of the natural PAH co-factor, allowing disease control in a subset of patients. Therefore, the purpose of this paper is to continue the work initiated with the expert survey paper, to provide national guidances aiming to harmonize and optimize patient care at a national level. Participants The Consensus Group, convened by 10 Steering Committee members, consisted of a multidisciplinary crowd of 46 experts in the management of PKU in Italy. Consensus process The Steering Committee met in a series of virtual meeting in order to discuss on clinical focuses to be developed and analyzed in guidance statements, on the basis of expert practice based evidence, large systematic literature review previously performed in the expert survey paper, and evidence based consensus published. Statements were re-discussed and refined during consensus conferences in the widest audience of experts, and finally submitted to the whole consensus group for a modified-Delphi voting. Results Seventy three statements, divided in two main clinical areas, PKU management and Pharmacotherapy, achieved large consensus in a multidisciplinary group of expert in different aspects of disease. Importantly, these statements involve guidances for the use of sapropterin dihydrochloride, still not sufficiently implemented in Italy, and a set of good practice to approach the use of novel enzyme replacement treatment pegvaliase. Conclusions This evidence-based consensus provides a minimum set of guidances for disease management to be implemented in all PKU centers. Moreover, these guidances represent the first statement for sapropterin dihydrochloride use, implementation and standardization in Italy, and a guide for approaching pegvaliase treatment at a national level on a consistent basis.

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“…While simple in theory, research demonstrates the return to strict adherence is extremely difficult [34], with many patients again nonadherent after several months. Based on recent data, new methods are emerging that can be effectively used to re-engage nonadherent PKU patients in their dietary management through a low burden regimen with immediate nutritional and possible mood benefits [35]. A stepwise approach with the overarching aim of achieving full dietary adherence over a set time may therefore be a more appropriate approach to facilitate patients’ return to the PKU diet but should be confirmed with further research.…”

Section: Discussionmentioning

confidence: 99%

Nutritional and Metabolic Characteristics of UK Adult Phenylketonuria Patients with Varying Dietary Adherence

et al. 2019

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The nutritional and metabolic characteristics of adult phenylketonuria (PKU) patients in the UK with varying dietary adherence is unknown. In other countries, nutritional and metabolic abnormalities have been reported in nonadherent patients compared to adherent counterparts. A pooled analysis of primary baseline data from two UK multi-centre studies was therefore performed to establish whether this is true from a UK perspective. Adult PKU patients who had provided 3-day food records and amino acid blood samples were included and grouped according to dietary adherence (adherent; n = 16 vs. nonadherent; n = 14). Nonadherent patients consumed greater amounts of natural protein compared to adherent patients (61.6 ± 30.7 vs. 18.3 ± 7.7 g/day; q < 0.001). In contrast, the contribution of protein substitutes to total protein intake was lower in nonadherent compared to adherent patients (3.9 ± 9.2 g/day vs. 58.6 ± 10.2 g/day; q < 0.001). Intakes of iron, zinc, vitamin D3, magnesium, calcium, selenium, iodine, vitamin C, vitamin A and copper were significantly lower in nonadherent compared to adherent patients and were below UK Reference Nutrient Intakes. Similarly, intakes of thiamin, riboflavin, niacin, vitamin B6 and phosphorus were significantly lower in nonadherent compared to adherent patients but met the UK Reference Nutrient Intakes. Phenylalanine concentrations in nonadherent patients were significantly higher than adherent patients (861 ± 348 vs. 464 ± 196 µmol/L; q = 0.040) and fell outside of European treatment target ranges. This study shows the nutritional and metabolic consequences of deviation from phenylalanine restriction and intake of PKU protein substitutes in nonadherent adult PKU patients. Collectively, these data further underlie the importance of life-long adherence to the PKU diet.

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Improved Eating Behaviour and Nutrient Intake in Noncompliant Patients with Phenylketonuria after Reintroducing a Protein Substitute: Observations from a Multicentre Study

Cited by 9 publications

References 33 publications

Large Neutral Amino Acid Therapy Increases Tyrosine Levels in Adult Patients with Phenylketonuria: A Long-Term Study

Large Neutral Amino Acid Therapy Increases Tyrosine Levels in Adult Patients with Phenylketonuria: A Long-Term Study

Italian national consensus statement on management and pharmacological treatment of phenylketonuria

Nutritional and Metabolic Characteristics of UK Adult Phenylketonuria Patients with Varying Dietary Adherence

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