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Dietetics and Nutritional Aspects in Inherited Metabolic Diseases (IMD)

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A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (15 September 2019) | Viewed by 59366

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Prof. Dr. Francjan J. Van Spronsen

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Department of Metabolic Diseases, Beatrix Children’s Hospital, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands
Interests: phenylketonuria; amino acids; metabolism; phenylalanine; tyrosine; succinylacetion; tyrosinemia; pediatrics
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Prof. Dr. Anita MacDonald

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Dietetic Department, Birmingham Children's Hospital, Steelhouse Lane, Birmingham B4 6NH, UK
Interests: phenylketonuria; dietary treatment; protein substitutes; dietary adherence; feeding development
Special Issues, Collections and Topics in MDPI journals

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Dear Colleagues,

The first treatable disease in the field of inherited metabolic diseases (IMD) was phenylketonuria (PKU). Not only was it the first to be treated, it was also the first disease that could be treated to prevent mental retardation, and moreover, not by a drug, but by dietary modification. Special medical formulae were produced in the hospital laboratory using recipes based on extensive lists of chemical ingredients. Scientists were generally skeptical about the impact of dietary treatment, and early, overzealous treatment was associated with inadequate growth, dietary deficiencies, poor development, and even death. Thereby, application of unproven dietary treatment in children required great courage by the early pioneers.

Knowing the early success of PKU dietary treatment, the early pioneers realized that the outcome of many more IMD conditions associated with high mortality or significant morbidity could be changed by dietary manipulation. This not only included IMD, affecting protein metabolism, but also carbohydrate and fat metabolism. The aims of dietary treatment differ according to the specific condition, but most dietary treated IMD are cause by the accumulation of substances that are toxic or affect normal function, or the effects of reduced ability to synthesize essential compounds. Conditions may be treated by adaptations to protein, fat, and carbohydrate intake, with supplementation with synthetic or modified protein, amino acids, triglycerides, or carbohydrate sources. This has led to the position of dieticians and nutritionists being pivotal in the field of IMD. Although the field of IMD is a relatively new specialty, we have significant dietary expertise with infants and children, and we are starting to gain expertise with adults. However, very little is known about the impact of the long-term use of synthetic diets in the elderly population, and even in infants and children there still is much to be learned.

The IMD field has expanded rapidly, but due to the rarity of conditions and a lack of research on IMD dietetic issues and IMD dieticians that dedicate their time to research, much of the current dietary practice is experience-generated rather than evidence-driven. This led to a remark in a Cochrane review that the diet in PKU was not proven to be necessary. Of course, few people would question the need to treat patients with PKU, but evidence is lacking to support many aspects of PKU dietary management even though this condition has been treated by diet for over 60 years. Evidence gaps must be addressed through systematic research, and this is why we welcome research manuscripts that study dietary treatments in IMD.

Prof. Francjan J. van Spronsen
Prof. Dr. Anita Macdonald
Guest Editors

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Keywords

phenylalanine
phenylketonuria
protein substitute
medical foods
amino acids
tyrosinaemia /tyrosinemia
maple syrup urine disease
nutritional support
protein
homocystinuria
dietary management
supplements
glycomacropeptide
protein tolerance
growth
organic acidurias
brain

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13 pages, 3008 KiB

Open AccessArticle

Mealtime Anxiety and Coping Behaviour in Parents and Children during Weaning in PKU: A Case-Control Study

by Sharon Evans, Anne Daly, Jo Wildgoose, Barbara Cochrane, Catherine Ashmore, Shauna Kearney and Anita MacDonald

Nutrients 2019, 11(12), 2857; https://doi.org/10.3390/nu11122857 - 21 Nov 2019

Cited by 2 | Viewed by 3548

Abstract

Solid food introduction may create anxiety for parents of children with phenylketonuria (PKU) due to the burden associated with protein substitute (PS) administration and natural protein restriction. In a longitudinal, prospective study, 20 mothers of children with PKU and 20 non-PKU control mothers completed 4 questionnaires (mealtime emotions, feed-time, Beck’s anxiety inventory and the coping health inventory for parents), examining parent/child mealtime emotions, anxiety, stress and coping strategies at child ages: weaning start, 8 months (m), 12 m, 15 m, 18 m and 24 m. Overall, mothers of children with PKU cope well with solid food introduction when applying a low-phenylalanine diet, with comparable low levels of stress and anxiety reported in both PKU and non-PKU groups. However, mothers of children with PKU reported peak scores in anxiety for emotive/cognitive symptoms at a child age of 15 m, and higher use of coping strategies at 15 m and 24 m (p < 0.05) of age. Generally, there was a trend that maternal anxiety regarding child rejection of PS increased with time, peaking between 12–24 m. In PKU, a child age of 12–18 m is identified as a key period when mothers feel most anxious/stressed with feeding, coinciding with raised blood phenylalanine levels probably associated with teething, illness and developing independence. Health professionals should be conscious of this vulnerable period and be prepared to offer more directional support as required. Full article

(This article belongs to the Special Issue Dietetics and Nutritional Aspects in Inherited Metabolic Diseases (IMD))

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11 pages, 1297 KiB

Open AccessArticle

The Effect of Various Doses of Phenylalanine Supplementation on Blood Phenylalanine and Tyrosine Concentrations in Tyrosinemia Type 1 Patients

by Willem G. van Ginkel, Hannah E. van Reemst, Nienke S. Kienstra, Anne Daly, Iris L. Rodenburg, Anita MacDonald, Johannes G.M. Burgerhof, Pim de Blaauw, Jennifer van de Krogt, Saikat Santra, M. Rebecca Heiner-Fokkema and Francjan J. van Spronsen

Nutrients 2019, 11(11), 2816; https://doi.org/10.3390/nu11112816 - 18 Nov 2019

Cited by 7 | Viewed by 4481

Abstract

Tyrosinemia type 1 (TT1) treatment with 2-(2-nitro-4-trifluormethyl-benzyl)-1,3-cyclohexanedione (NTBC) and a phenylalanine-tyrosine restricted diet is associated with low phenylalanine concentrations. Phenylalanine supplementation is prescribed without comprehensive consideration about its effect on metabolic control. We investigated the effect of phenylalanine supplementation on bloodspot phenylalanine, tyrosine, NTBC and succinylacetone. Eleven TT1 patients received 0, 20 and 40 mg/kg/day phenylalanine supplementation with the phenylalanine-tyrosine free L-amino acid supplements. Bloodspots were collected before breakfast, midday and evening meal. Differences between study periods, sample times and days within a study period were studied using (generalized) linear mixed model analyses. Twenty and 40 mg/kg/day phenylalanine supplementation prevented daytime phenylalanine decreases (p = 0.05) and most low phenylalanine concentrations, while tyrosine concentrations increased (p < 0.001). Furthermore, NTBC and succinylacetone concentrations did not differ between study periods. To conclude, 20 mg/kg/day phenylalanine supplementation can prevent most low phenylalanine concentrations without increasing tyrosine to concentrations above the target range or influencing NTBC and succinylacetone concentrations, while 40 mg/kg/day increased tyrosine concentrations to values above the targeted range. Additionally, this study showed that the effect of phenylalanine supplementation, and a possible phenylalanine deficiency, should be assessed using pre-midday meal blood samples that could be combined with an overnight fasted sample when in doubt. Full article

(This article belongs to the Special Issue Dietetics and Nutritional Aspects in Inherited Metabolic Diseases (IMD))

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10 pages, 228 KiB

Open AccessArticle

Untreated PKU Patients without Intellectual Disability: What Do They Teach Us?

by Danique van Vliet, Annemiek M.J. van Wegberg, Kirsten Ahring, Miroslaw Bik-Multanowski, Kari Casas, Bozena Didycz, Maja Djordjevic, Jozef L. Hertecant, Vincenzo Leuzzi, Per Mathisen, Francesca Nardecchia, Kimberly K. Powell, Frank Rutsch, Maja Stojiljkovic, Fritz K. Trefz, Natalia Usurelu, Callum Wilson, Clara D. van Karnebeek, William B. Hanley and Francjan J. van Spronsen

Nutrients 2019, 11(11), 2572; https://doi.org/10.3390/nu11112572 - 25 Oct 2019

Cited by 17 | Viewed by 5098

Abstract

Phenylketonuria (PKU) management is aimed at preventing neurocognitive and psychosocial dysfunction by keeping plasma phenylalanine concentrations within the recommended target range. It can be questioned, however, whether universal plasma phenylalanine target levels would result in optimal neurocognitive outcomes for all patients, as similar plasma phenylalanine concentrations do not seem to have the same consequences to the brain for each PKU individual. To better understand the inter-individual differences in brain vulnerability to high plasma phenylalanine concentrations, we aimed to identify untreated and/or late-diagnosed PKU patients with near-normal outcome, despite high plasma phenylalanine concentrations, who are still alive. In total, we identified 16 such cases. While intellectual functioning in these patients was relatively unaffected, they often did present other neurological, psychological, and behavioral problems. Thereby, these “unusual” PKU patients show that the classical symptomatology of untreated or late-treated PKU may have to be rewritten. Moreover, these cases show that a lack of intellectual dysfunction despite high plasma phenylalanine concentrations does not necessarily imply that these high phenylalanine concentrations have not been toxic to the brain. Also, these cases may suggest that different mechanisms are involved in PKU pathophysiology, of which the relative importance seems to differ between patients and possibly also with increasing age. Further research should aim to better distinguish PKU patients with respect to their cerebral effects to high plasma phenylalanine concentrations. Full article

(This article belongs to the Special Issue Dietetics and Nutritional Aspects in Inherited Metabolic Diseases (IMD))

14 pages, 1893 KiB

Open AccessArticle

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

by Alessandro P. Burlina, Chiara Cazzorla, Pamela Massa, Giulia Polo, Christian Loro, Daniela Gueraldi and Alberto B. Burlina

Nutrients 2019, 11(10), 2541; https://doi.org/10.3390/nu11102541 - 21 Oct 2019

Cited by 14 | Viewed by 5958

Abstract

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. Full article

(This article belongs to the Special Issue Dietetics and Nutritional Aspects in Inherited Metabolic Diseases (IMD))

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13 pages, 2363 KiB

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Blood and Brain Biochemistry and Behaviour in NTBC and Dietary Treated Tyrosinemia Type 1 Mice

by Willem G. van Ginkel, Danique van Vliet, Els van der Goot, Martijn H. J. R. Faassen, Arndt Vogel, M. Rebecca Heiner-Fokkema, Eddy. A. van der Zee and Francjan J. van Spronsen

Nutrients 2019, 11(10), 2486; https://doi.org/10.3390/nu11102486 - 16 Oct 2019

Cited by 7 | Viewed by 3771

Abstract

Tyrosinemia type 1 (TT1) is a rare metabolic disease caused by a defect in the tyrosine degradation pathway. Neurocognitive deficiencies have been described in TT1 patients, that have, among others, been related to changes in plasma large neutral amino acids (LNAA) that could result in changes in brain LNAA and neurotransmitter concentrations. Therefore, this project aimed to investigate plasma and brain LNAA, brain neurotransmitter concentrations and behavior in C57 Bl/6 fumarylacetoacetate hydrolase deficient (FAH−/−) mice treated with 2-(2-nitro-4-trifluoromethylbenoyl)-1,3-cyclohexanedione (NTBC) and/or diet and wild-type mice. Plasma and brain tyrosine concentrations were clearly increased in all NTBC treated animals, even with diet (p < 0.001). Plasma and brain phenylalanine concentrations tended to be lower in all FAH−/− mice. Other brain LNAA, were often slightly lower in NTBC treated FAH−/− mice. Brain neurotransmitter concentrations were usually within a normal range, although serotonin was negatively correlated with brain tyrosine concentrations (p < 0.001). No clear behavioral differences between the different groups of mice could be found. To conclude, this is the first study measuring plasma and brain biochemistry in FAH−/− mice. Clear changes in plasma and brain LNAA have been shown. Further research should be done to relate the biochemical changes to neurocognitive impairments in TT1 patients. Full article

(This article belongs to the Special Issue Dietetics and Nutritional Aspects in Inherited Metabolic Diseases (IMD))

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13 pages, 900 KiB

Open AccessArticle

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

by Benjamin Green, Robert Browne, Sarah Firman, Melanie Hill, Yusof Rahman, Kit Kaalund Hansen, Sarah Adam, Rachel Skeath, Paula Hallam, Ide Herlihy, Fiona Jenkinson, Claire Nicol, Sandra Adams, Lisa Gaff, Sarah Donald, Charlotte Dawson, Louise Robertson, Carla Fitzachary, Heidi Chan, Arlene Slabbert, Carolyn Dunlop, Alison Cozens, Camille Newby, Victoria Bittle, Gary Hubbard and Rebecca Stratton Show full author list Hide full author list

Nutrients 2019, 11(10), 2459; https://doi.org/10.3390/nu11102459 - 14 Oct 2019

Cited by 24 | Viewed by 5248

Abstract

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. Full article

(This article belongs to the Special Issue Dietetics and Nutritional Aspects in Inherited Metabolic Diseases (IMD))

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14 pages, 1988 KiB

Open AccessArticle

The Benefit of Large Neutral Amino Acid Supplementation to a Liberalized Phenylalanine-Restricted Diet in Adult Phenylketonuria Patients: Evidence from Adult Pah-Enu2 Mice

by Danique van Vliet, Els van der Goot, Wiggert G. van Ginkel, Martijn H. J. R. van Faassen, Pim de Blaauw, Ido P. Kema, Aurora Martinez, M. Rebecca Heiner-Fokkema, Eddy A. van der Zee and Francjan J. van Spronsen

Nutrients 2019, 11(9), 2252; https://doi.org/10.3390/nu11092252 - 19 Sep 2019

Cited by 11 | Viewed by 5116

Abstract

Many phenylketonuria (PKU) patients cannot adhere to the severe dietary restrictions as advised by the European PKU guidelines, which can be accompanied by aggravated neuropsychological impairments that, at least in part, have been attributed to brain monoaminergic neurotransmitter deficiencies. Supplementation of large neutral amino acids (LNAA) to an unrestricted diet has previously been shown to effectively improve brain monoamines in PKU mice of various ages. To determine the additive value of LNAA supplementation to a liberalized phenylalanine-restricted diet, brain and plasma monoamine and amino acid concentrations in 10 to 16-month-old adult C57Bl/6 PKU mice on a less severe phenylalanine-restricted diet with LNAA supplementation were compared to those on a non-supplemented severe or less severe phenylalanine-restricted diet. LNAA supplementation to a less severe phenylalanine-restricted diet was found to improve both brain monoamine and phenylalanine concentrations. Compared to a severe phenylalanine-restricted diet, it was equally effective to restore brain norepinephrine and serotonin even though being less effective to reduce brain phenylalanine concentrations. These results in adult PKU mice support the idea that LNAA supplementation may enhance the effect of a less severe phenylalanine-restricted diet and suggest that cerebral outcome of PKU patients treated with a less severe phenylalanine-restricted diet may be helped by additional LNAA treatment. Full article

(This article belongs to the Special Issue Dietetics and Nutritional Aspects in Inherited Metabolic Diseases (IMD))

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12 pages, 823 KiB

Open AccessArticle

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

by Benjamin Green, Yusof Rahman, Sarah Firman, Sarah Adam, Fiona Jenkinson, Claire Nicol, Sandra Adams, Charlotte Dawson, Louise Robertson, Carolyn Dunlop, Alison Cozens, Gary Hubbard and Rebecca Stratton

Nutrients 2019, 11(9), 2035; https://doi.org/10.3390/nu11092035 - 30 Aug 2019

Cited by 9 | Viewed by 4502

Abstract

Noncompliance is widespread in adults with PKU and is associated with adverse metabolic, nutritional and cognitive abnormalities. Returning to the PKU diet is important for this at-risk population, yet for many this is challenging to achieve. Strategies that ease the return to the PKU diet, while offering nutritional and cognitive advantages, are needed. Twelve PKU adults (33.7 ± 2.6 years), who had been noncompliant for 4.5 years (range: 1 to 11 years), took 33 g of a low-volume, nutrient-enriched, protein substitute daily for 28 days. Outcomes of eating behaviour, nutrient intake and mood were assessed at entry (baseline, days 1–3) and after the intervention period (days 29–31). At baseline, intakes of natural protein and estimated phenylalanine were high (66.4 g and 3318.5 mg, respectively) and intakes of calcium, magnesium, iron, zinc, iodine and vitamin D were below country-specific recommendations. With use of the experimental protein substitute, natural protein and estimated phenylalanine intake declined (p = 0.043 for both). Fat and saturated fat intakes also decreased (p = 0.019 and p = 0.041, respectively), while energy and carbohydrate intake remained unchanged. Micronutrient intake increased (p ≤ 0.05 for all aforementioned) to levels well within reference nutrient intake recommendations. Blood vitamin B₁₂ and vitamin D increased by 19.8% and 10.4%, respectively. Reductions in anxiety and confusion were also observed during the course of the study yet should be handled as preliminary data. This study demonstrates that reintroducing a low-volume, nutrient-enriched protein substitute delivers favourable nutritional and possible mood benefits in noncompliant PKU patients, yet longer-term studies are needed to further confirm this. This preliminary knowledge should be used in the design of new strategies to better facilitate patients’ return to the PKU diet, with the approach described here as a foundation. Full article

(This article belongs to the Special Issue Dietetics and Nutritional Aspects in Inherited Metabolic Diseases (IMD))

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10 pages, 709 KiB

Open AccessArticle

Biomarkers of Micronutrients in Regular Follow-Up for Tyrosinemia Type 1 and Phenylketonuria Patients

by Kimber van Vliet, Iris L. Rodenburg, Willem G. van Ginkel, Charlotte M.A. Lubout, Bruce H.R. Wolffenbuttel, Melanie M. van der Klauw, M. Rebecca Heiner-Fokkema and Francjan J. van Spronsen

Nutrients 2019, 11(9), 2011; https://doi.org/10.3390/nu11092011 - 27 Aug 2019

Cited by 7 | Viewed by 4427

Abstract

Phenylketonuria (PKU) is treated with dietary restrictions and sometimes tetrahydrobiopterin (BH4). PKU patients are at risk for developing micronutrient deficiencies, such as vitamin B12 and folic acid, likely due to their diet. Tyrosinemia type 1 (TT1) is similar to PKU in both pathogenesis and treatment. TT1 patients follow a similar diet, but nutritional deficiencies have not been investigated yet. In this retrospective study, biomarkers of micronutrients in TT1 and PKU patients were investigated and outcomes were correlated to dietary intake and anthropometric measurements from regular follow-up measurements from patients attending the outpatient clinic. Data was analyzed using Kruskal–Wallis, Fisher’s exact and Spearman correlation tests. Furthermore, descriptive data were used. Overall, similar results for TT1 and PKU patients (with and without BH4) were observed. In all groups high vitamin B12 concentrations were seen rather than B12 deficiencies. Furthermore, all groups showed biochemical evidence of vitamin D deficiency. This study shows that micronutrients in TT1 and PKU patients are similar and often within the normal ranges and that vitamin D concentrations could be optimized. Full article

(This article belongs to the Special Issue Dietetics and Nutritional Aspects in Inherited Metabolic Diseases (IMD))

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10 pages, 906 KiB

Open AccessArticle

Over Restriction of Dietary Protein Allowance: The Importance of Ongoing Reassessment of Natural Protein Tolerance in Phenylketonuria

by Alex Pinto, Manuela Ferreira Almeida, Anita MacDonald, Paula Cristina Ramos, Sara Rocha, Arlindo Guimas, Rosa Ribeiro, Esmeralda Martins, Anabela Bandeira, Richard Jackson, Francjan van Spronsen, Anne Payne and Júlio César Rocha

Nutrients 2019, 11(5), 995; https://doi.org/10.3390/nu11050995 - 30 Apr 2019

Cited by 15 | Viewed by 5312

Abstract

Phenylalanine (Phe) tolerance is highly variable in phenylketonuria (PKU) and rarely described in patients aged ≥12 years. Patients ≥12 years of age with PKU were systematically challenged with additional natural protein (NP) if blood Phe levels remained below 480 µmol/L (i.e., upper target blood Phe level for patients aged ≥12 years using Portuguese PKU guidelines). In PKU patients, NP tolerance was calculated at baseline and a median of 6 months after systematic challenge with NP whilst patients were maintaining a blood Phe ≤480 μmol/L. Anthropometry was assessed at both times. Routine blood Phe levels were collected. We studied 40 well-controlled PKU patients (10 hyperphenylalaninemia (HPA), 23 mild and 7 classic PKU), on a low-Phe diet with a mean age of 17 years (12–29 years). Median daily NP intake significantly increased between assessments (35 vs. 40 g/day, p = 0.01). Twenty-six patients (65%) were able to increase their median NP intake by a median 12 g/day (2–42 g)/day and still maintain blood Phe within target range. Out of the previous 26 patients, 20 (77%) (8 HPA, 11 mild and 1 classical PKU) increased NP from animal sources (e.g., dairy products, fish and meat) and 6 patients (23%) (3 mild and 3 classical PKU) from plant foods (bread, pasta, potatoes). Median protein equivalent intake from Phe-free/low-Phe protein substitute decreased (0.82 vs. 0.75 g/kg, p = 0.01), while median blood Phe levels remained unchanged (279 vs. 288 μmol/L, p = 0.06). Almost two-thirds of patients with PKU tolerated additional NP when challenged and still maintained blood Phe within the national target range. This suggests that some patients with PKU treated by a low-Phe diet only may over restrict their NP intake. In order to minimise the burden of treatment and optimise NP intake, it is important to challenge with additional NP at periodic intervals. Full article

(This article belongs to the Special Issue Dietetics and Nutritional Aspects in Inherited Metabolic Diseases (IMD))

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22 pages, 2317 KiB

Open AccessReview

Long-Term Growth in Phenylketonuria: A Systematic Review and Meta-Analysis

by Fatma Ilgaz, Alex Pinto, Hülya Gökmen-Özel, Julio César Rocha, Esther van Dam, Kirsten Ahring, Amaya Bélanger-Quintana, Katharina Dokoupil, Erdem Karabulut and Anita MacDonald

Nutrients 2019, 11(9), 2070; https://doi.org/10.3390/nu11092070 - 3 Sep 2019

Cited by 22 | Viewed by 6153

Abstract

There is an ongoing debate regarding the impact of phenylketonuria (PKU) and its treatment on growth. To date, evidence from studies is inconsistent, and data on the whole developmental period is limited. The primary aim of this systematic review was to investigate the effects of a phenylalanine (Phe)-restricted diet on long-term growth in patients with PKU. Four electronic databases were searched for articles published until September 2018. A total of 887 results were found, but only 13 articles met eligibility criteria. Only three studies had an adequate methodology for meta-analysis. Although the results indicate normal growth at birth and during infancy, children with PKU were significantly shorter and had lower weight for age than reference populations during the first four years of life. Impaired linear growth was observed until the end of adolescence in PKU. In contrast, growth impairment was not reported in patients with mild hyperphenylalaninemia, not requiring dietary restriction. Current evidence indicates that even with advances in dietary treatments, “optimal” growth outcomes are not attained in PKU. The majority of studies include children born before 1990s, so further research is needed to show the effects of recent dietary practices on growth in PKU. Full article

(This article belongs to the Special Issue Dietetics and Nutritional Aspects in Inherited Metabolic Diseases (IMD))

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14 pages, 516 KiB

Open AccessReview

Effects of LC-PUFA Supplementation in Patients with Phenylketonuria: A Systematic Review of Controlled Trials

by María Luz Couce, María José de Castro, Carmela de Lamas and Rosaura Leis

Nutrients 2019, 11(7), 1537; https://doi.org/10.3390/nu11071537 - 6 Jul 2019

Cited by 6 | Viewed by 4081

Abstract

Evidence suggests a role of long chain polyunsaturated fatty acids (LC-PUFA), in which animal foods are especially rich, in optimal neural development. The LC-PUFAs docosahexaenoic acid (DHA) and arachidonic acid, found in high concentrations in the brain and retina, have potential beneficial effects on cognition, and motor and visual functions. Phenylketonuria (PKU) is the most common inborn error of amino acid metabolism. The treatment of PKU consists of a phenylalanine-free diet, which limits the intake of natural proteins of high biological value. In this systematic review, we summarize the available evidence supporting a role for LC-PUFA supplementation as an effective means of increasing LC-PUFA levels and improving visual and neurocognitive functions in PKU patients. Data from controlled trials of children and adults (up to 47 years of age) were obtained by searching the MEDLINE and SCOPUS databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. For each selected study, the risk of bias was assessed applying the methodology of the Cochrane Collaboration. The findings indicate that DHA supplementation in PKU patients from 2 weeks to 47 years of age improves DHA status and decreases visual evoked potential P100 wave latency in PKU children from 1 to 11 years old. Neurocognitive data are inconclusive. Full article

(This article belongs to the Special Issue Dietetics and Nutritional Aspects in Inherited Metabolic Diseases (IMD))

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