Retrospective Evaluation of Diet Compliance on Plasma Amino Acid and Vitamin Levels in Patients with Phenylketonuria

Abstract

Retrospective Evaluation of Diet Compliance on Plasma Amino Acid and Vitamin Levels in Patients with Phenylketonuria

Abstract

Purpose: In this study, it was aimed to compare the plasma amino acid and blood vitamin/mineral levels in patients with classical phenylketonuria and healthy controls. Material and Methods: 54 patients with classical phenylketonuria and 22 healthy controls (76 children, 47 boys, 61.8%) were included in the study. The patient group was divided into two subgroups as high adherence to phenylalanine-restricted diet (HAD, 16 patients) and low adherence to this diet (LAD, 38 patients) according to the mean plasma phenylalanine level of the patients of the previous year. Anthropometric measurements (body weight and height and standard deviation score values), plasma phenylalanine and other amino acid levels, hemoglobin, vitamin B12, folic acid, vitamin D, zinc, ferritin levels of all groups were recorded. Results: The mean age of the entire study group was 10.1 ± 3.6 (minimum: 3.5 - maximum: 17) years. There was no significant difference between the phenylketonuria group and the control group in terms of age, gender distribution and anthropometric data. There was a significant difference between the three groups in terms of plasma phenylalanine levels (plasma phenylalanine levels 299.0 ± 77.2; 813.7 ± 356.6 and 47.5 ± 15.9 µmol/L in HAD, LAD and control groups respectively, p= 0.001). Tryptophan was significantly lower in the HAD group than in the LAD and control groups (p= 0.001 and p= 0.006, respectively). Lysine was found to be significantly higher and histidine was lower in the HAD group than the control group (p= 0.016 and p= 0.008, respectively). Hemoglobin, vitamin B12, folic acid and 25-OH vitamin D levels were found to be significantly higher in the PKU patient group compared to healthy children and no difference between zinc and ferritin levels. Conclusion: As a result, in patients with phenylketonuria who comply with the diet and whose anthropometric data are in the normal range, no significant deterioration in vitamin/mineral and amino acid values is observed. Compliance of the patients with a diet restricted from phenylalanine will both reduce the neurological effects and ensure that the patient is nutritionally balanced.

Keywords

• Classical phenylketonuria
• phenylalanine-restricted diet
• hemoglobin
• plasma amino acids
• vitamins

References

1. Odagiri S, Kabata D, Tomita S, et al. Clinical and genetic characteristics of patients with mild hyperphenylalaninemia identified by Newborn Screening Program in Japan. Int J Neonatal Screen 2021;7(1):17.
2. Elhawary NA, AlJahdali IA, Abumansour IS, et al. Genetic etiology and clinical challenges of phenylketonuria. Hum Genomics 2022;16(1):22.
3. Opladen T, López-Laso E, Cortès-Saladelafont E, et al. International working group on Neurotransmitter related Disorders (iNTD). Consensus guideline for the diagnosis and treatment of tetrahydrobiopterin (BH4) deficiencies. Orphanet J Rare Dis 2020;15(1):126.
4. Blau N, Martinez A, Hoffmann GF, Thöny B. DNAJC12 deficiency: A new strategy in the diagnosis of hyperphenylalaninemias. Mol Genet Metab 2018;123(1):1-5.
5. Kose E, Arslan N. Vitamin/mineral and micronutrient status in patients with classical phenylketonuria. Clin Nutr 2019;38(1):197-203.
6. Robert M, Rocha JC, van Rijn M, et al. Micronutrient status in phenylketonuria. Mol Genet Metab 2013;110 Suppl: S6-17.
7. Guthrie R, Susi A. A simple phenylalanine method for detecting phenylketonuria in large populations of newborn infants. Pediatrics 1963; 32, 338-343.
8. Newborn Screening Programme, 2014, Available from: www.ihsm.gov.tr/indir/acsap/yenidogan_tarama_programi.doc

9. Crujeiras V, Aldámiz-Echevarría L, Dalmau J, et al. Vitamin and mineral status in patients with hyperphenylalaninemia. Mol Genet Metab 2015;115(4):145-50.
10. de Romaña DL, Olivares M, Uauy R, Araya M. Risks and benefits of copper in light of new insights of copper homeostasis. J Trace Elem Med Biol 2011;25(1):3-13.
11. Lin CN, Wilson A, Church BB, et al. Pediatric reference intervals for serum copper and zinc. Clin Chim Acta 2012;413(5-6):612-5.
12. Akış M, Kant M, Işık İ, et al. Functional vitamin B12 deficiency in phenylketonuria patients and healthy controls: An evaluation with combined indicator of vitamin B12 status as a biochemical index. Ann Clin Biochem 2020;57(4):291-299.
13. Arnold GL, Kirby R, Preston C, Blakely E. Iron and protein sufficiency and red cell indices in phenylketonuria. J Am Coll Nutr 2001;20(1):65-70.
14. Tummolo A, Carella R, Paterno G, et al. Body composition in adolescent PKU patients: beyond fat mass. Children (Basel) 2022;9(9):1353.
15. Rodrigues C, Pinto A, Faria A, et al. Is the phenylalanine-restricted diet a risk factor for overweight or obesity in patients with phenylketonuria (PKU)? A Systematic Review and Meta-Analysis. Nutrients 2021;13(10):3443.
16. Tankeu AT, Pavlidou DC, Superti-Furga A, Gariani K, Tran C. Overweight and obesity in adult patients with phenylketonuria: a systematic review. Orphanet J Rare Dis 2023;18(1):37.
17. Demirdas S, van Spronsen FJ, Hollak CM, et al. Micronutrients, Essential Fatty Acids and Bone Health in Phenylketonuria. Ann Nutr Metab 2017;70(2):111-121.
18. Bokayeva K, Jamka M, Walkowiak D, et al. Vitamin status in patients with phenylketonuria: A systematic review and meta-analysis. Int J Mol Sci 2024;25(10):5065.
19. Montoya Parra GA, Singh RH, Cetinyurek YA, Kuhn M, MacDonald A. status of nutrients important in brain function in phenylketonuria: a systematic review and meta-analysis. Orphanet J Rare Dis 2018;13(1):101.
20. de Almeida BNF, Laufer JA, Mezzomo TR, et al. Nutritional and metabolic parameters of children and adolescents with phenylketonuria. Clin Nutr ESPEN 2020; 37:44-49.
21. Ahmadzadeh M, Sohrab G, Alaei M, et al. Growth and nutritional status of phenylketonuric children and adolescents. BMC Pediatr.2022;22(1):664.
22. Stølen LH, Lilje R, Jørgensen JV, Bliksrud YT, Almaas R. High dietary folic acid and high plasma folate in children and adults with phenylketonuria. JIMD Rep 2014;13:83-90.
23. Wan Z, Rosenbaum ER, Liu W, et al. Benchmark examination of blood amino acids patterns in phenylketonuria neonates and young children on phenylalanine restricted dietary treatment. Fetal Pediatr Pathol 2022;41(3):443-450.
24. Liang L, Ye J, Han L, et al. Examining the blood amino acid status in pretherapeutic patients with hyperphenylalaninemia. J Clin Lab Anal 2020;34(3): e23106.
25. Scheinin M, Barassi A, Junnila J, et al. Amino acid plasma profiles from a prolonged-release protein substitute for phenylketonuria: A randomized, single-dose, four-way crossover trial in healthy volunteers. Nutrients 2020;12(6):1653.
26. Matuszewska E, Matysiak J, Kałużny Ł, et al. Amino acid profile alterations in phenylketonuria: implications for clinical practice. Metabolites 2024;14(7):397.