Original Paper Ann Nutr Metab 2014;65:42–48 DOI: 10.1159/000363391
Received: November 19, 2013 Accepted after revision: April 30, 2014 Published online: September 4, 2014
The Micronutrient Status of Patients with Phenylketonuria on Dietary Treatment: An Ongoing Challenge Sharon Evans Anne Daly John MacDonald Mary Anne Preece Saikat Santra Suresh Vijay Anupam Chakrapani Anita MacDonald Birmingham Children’s Hospital, Birmingham, UK
Abstract Background: In phenylketonuria (PKU), phenylalanine-free L-amino acid supplements are the major source of dietary micronutrients. Methods: Four hundred fifty-two retrospective annual/bi-annual non-fasting blood samples for nutritional markers (plasma zinc, selenium, and serum folate) from 78 subjects aged 1–16 years (median number of blood samples: 6, range 1–14) were analysed over 12 years. Longitudinal blood result data were available for 51 subjects (65%). The dietary intake from supplements was calculated. Results: The median intakes of all of the micronutrients studied were >200% of the reference nutrient intakes (RNI). There was no statistical correlation between dietary intake and nutritional markers outside of the normal reference range (RR) except for selenium, but there was a correlation between a lower plasma zinc, plasma selenium and haemoglobin status and better blood phenylalanine control in 1- to 4-year-old children. On at least one occasion, the individual plasma concentrations of zinc (71%, n = 54/76) and selenium (21%,
© 2014 S. Karger AG, Basel 0250–6807/14/0651–0042$39.50/0 E-Mail [email protected] www.karger.com/anm
n = 16/75) were below the RR; however, the concentrations of selenium (41%, n = 31/75) and serum folate (83%, n = 34/41) were also above the RR. Dietary intakes exceeded the upper tolerable intakes for zinc and copper (32%, n = 25) and folate (65%, n = 51). Individual longitudinal data demonstrated little change in micronutrient status over time. Conclusions: In PKU, biochemical micronutrient deficiencies are common despite micronutrient intakes above the RNI. Further study of the nutritional profiling of L-amino acid supplements in PKU is needed. © 2014 S. Karger AG, Basel
Introduction
In phenylketonuria (PKU), a strict low-phenylalanine diet is associated with the risk of developing vitamin and mineral deficiencies due to a severe restriction of natural protein intake, commonly to less than 10 g/day. Highbiological-protein foods are replaced by a phenylalaninefree (phe-free) L-amino acid supplement. Over the last 20 years, there has been an increasing trend of adding vitamins, minerals and trace mineral supplements to phefree L-amino acids [1]. Practically, this reduces the total number of special dietary supplements required each Sharon Evans Dietetic Department, Birmingham Children’s Hospital Steelhouse Lane Birmingham B4 6NH (UK) E-Mail evanss21 @ me.com
Downloaded by: Stockholm University Library 130.237.165.40 - 2/23/2018 9:47:51 PM
Key Words Metabolic disorders · Nutritional biochemistry · Clinical nutrition · Human nutrition · Phenylketonuria · Phenylalanine · Micronutrients · Protein substitutes
Materials and Methods Subjects All children aged 1–16 years diagnosed with PKU identified by newborn screening and treated within the first 21 days of life, from one IMD centre, were included if they had had at least one nutritional blood screening during 1999–2011. All were on a low-phenylalanine diet supplemented with a phe-free L-amino acid supplement. The total prescribed dietary protein intake from natural protein and phe-free L-amino acids was: ages 1–3 years, 3 g/kg/day; ages 4–5 years, 2.5 g/kg/day; ages 6–10 years, 2 g/kg/day, and ages >10 years, 1–1.5 g to a maximum of 80 g/day. Fruits and vegetables containing 2 blood samples and 58% (n = 45) had ≥5. Sixty-five per cent (n = 51) of the subjects had blood samples in more than one age band. No clinical signs of deficiency were documented.
44
Subjects with results above the RR, % (n)
Ann Nutr Metab 2014;65:42–48 DOI: 10.1159/000363391
Zinc In almost one third (n = 114) of all samples, the plasma zinc level was below the RR for age, and 71% (n = 54/76) of the subjects had zinc levels below the RR at some time point (table 1). This was predominantly in children aged 1/3 of subMicronutrient Status in PKU
jects) had at least one plasma selenium level below the RR. The median selenium intake (%RNI) on micronutrientsupplemented phe-free L-amino acids was 220% (range 70–597); for separate vitamin and mineral supplementation it was 167% (range 73–373) (table 2). In children aged 5–10 years with plasma selenium concentrations above the normal RR, this was associated with a higher dietary intake of selenium (p = 0.008; Mann-Whitney test, 95% CI). Iron Thirty-six per cent (n = 27) of children had at least one haemoglobin level below the normal RR for age (table 1), although this improved with age. Only 12% (n = 9) of subjects had an MCV below the RR, and this occurred only in those aged
Received: November 19, 2013 Accepted after revision: April 30, 2014 Published online: September 4, 2014
The Micronutrient Status of Patients with Phenylketonuria on Dietary Treatment: An Ongoing Challenge Sharon Evans Anne Daly John MacDonald Mary Anne Preece Saikat Santra Suresh Vijay Anupam Chakrapani Anita MacDonald Birmingham Children’s Hospital, Birmingham, UK
Abstract Background: In phenylketonuria (PKU), phenylalanine-free L-amino acid supplements are the major source of dietary micronutrients. Methods: Four hundred fifty-two retrospective annual/bi-annual non-fasting blood samples for nutritional markers (plasma zinc, selenium, and serum folate) from 78 subjects aged 1–16 years (median number of blood samples: 6, range 1–14) were analysed over 12 years. Longitudinal blood result data were available for 51 subjects (65%). The dietary intake from supplements was calculated. Results: The median intakes of all of the micronutrients studied were >200% of the reference nutrient intakes (RNI). There was no statistical correlation between dietary intake and nutritional markers outside of the normal reference range (RR) except for selenium, but there was a correlation between a lower plasma zinc, plasma selenium and haemoglobin status and better blood phenylalanine control in 1- to 4-year-old children. On at least one occasion, the individual plasma concentrations of zinc (71%, n = 54/76) and selenium (21%,
© 2014 S. Karger AG, Basel 0250–6807/14/0651–0042$39.50/0 E-Mail [email protected] www.karger.com/anm
n = 16/75) were below the RR; however, the concentrations of selenium (41%, n = 31/75) and serum folate (83%, n = 34/41) were also above the RR. Dietary intakes exceeded the upper tolerable intakes for zinc and copper (32%, n = 25) and folate (65%, n = 51). Individual longitudinal data demonstrated little change in micronutrient status over time. Conclusions: In PKU, biochemical micronutrient deficiencies are common despite micronutrient intakes above the RNI. Further study of the nutritional profiling of L-amino acid supplements in PKU is needed. © 2014 S. Karger AG, Basel
Introduction
In phenylketonuria (PKU), a strict low-phenylalanine diet is associated with the risk of developing vitamin and mineral deficiencies due to a severe restriction of natural protein intake, commonly to less than 10 g/day. Highbiological-protein foods are replaced by a phenylalaninefree (phe-free) L-amino acid supplement. Over the last 20 years, there has been an increasing trend of adding vitamins, minerals and trace mineral supplements to phefree L-amino acids [1]. Practically, this reduces the total number of special dietary supplements required each Sharon Evans Dietetic Department, Birmingham Children’s Hospital Steelhouse Lane Birmingham B4 6NH (UK) E-Mail evanss21 @ me.com
Downloaded by: Stockholm University Library 130.237.165.40 - 2/23/2018 9:47:51 PM
Key Words Metabolic disorders · Nutritional biochemistry · Clinical nutrition · Human nutrition · Phenylketonuria · Phenylalanine · Micronutrients · Protein substitutes
Materials and Methods Subjects All children aged 1–16 years diagnosed with PKU identified by newborn screening and treated within the first 21 days of life, from one IMD centre, were included if they had had at least one nutritional blood screening during 1999–2011. All were on a low-phenylalanine diet supplemented with a phe-free L-amino acid supplement. The total prescribed dietary protein intake from natural protein and phe-free L-amino acids was: ages 1–3 years, 3 g/kg/day; ages 4–5 years, 2.5 g/kg/day; ages 6–10 years, 2 g/kg/day, and ages >10 years, 1–1.5 g to a maximum of 80 g/day. Fruits and vegetables containing 2 blood samples and 58% (n = 45) had ≥5. Sixty-five per cent (n = 51) of the subjects had blood samples in more than one age band. No clinical signs of deficiency were documented.
44
Subjects with results above the RR, % (n)
Ann Nutr Metab 2014;65:42–48 DOI: 10.1159/000363391
Zinc In almost one third (n = 114) of all samples, the plasma zinc level was below the RR for age, and 71% (n = 54/76) of the subjects had zinc levels below the RR at some time point (table 1). This was predominantly in children aged 1/3 of subMicronutrient Status in PKU
jects) had at least one plasma selenium level below the RR. The median selenium intake (%RNI) on micronutrientsupplemented phe-free L-amino acids was 220% (range 70–597); for separate vitamin and mineral supplementation it was 167% (range 73–373) (table 2). In children aged 5–10 years with plasma selenium concentrations above the normal RR, this was associated with a higher dietary intake of selenium (p = 0.008; Mann-Whitney test, 95% CI). Iron Thirty-six per cent (n = 27) of children had at least one haemoglobin level below the normal RR for age (table 1), although this improved with age. Only 12% (n = 9) of subjects had an MCV below the RR, and this occurred only in those aged
