Nutrition Management of Inherited Metabolic Diseases

This research group aims to contribute to the production and synthesis of scientific evidence related with hereditary diseases associated with metabolism. 

This group integrates national and international networks, namely the Society for the Study of Inborn Errors of Metabolism, the Nutrition Working Group of the European Phenylketonuria Guidelines of the European Society for Phenylketonuria and Allied Disorders Treated as Phenylketonuria and the Portuguese Society for Metabolic Disorders. The main research areas include clinical, epidemiological and nutritional intervention studies aimed for improving the clinical practice and thus contributing to the optimization of patient metabolic control, a better prognosis, but also the synthesis of scientific evidence to support clinical practice and policy-making.

Graphical Abstract
  • Trends in Nutritional Status of Patients with Phenylketonuria (TNSPKU)

Summary
Phenylketonuria (PKU) is the most frequent inborn error of amino acid metabolism. In the great majority of patients (98%), this autosomal recessive disorder is caused by an impaired activity of the hepatic enzyme phenylalanine hydroxylase (PAH). This enzyme is responsible for the hepatic hydroxylation of phenylalanine (Phe) into tyrosine, in the presence of its cofactor, tetrahydrobiopterin (BH4). The mainstay of treatment is a special diet characterized by a natural protein restriction, supplemented with protein substitutes and special low protein foods, aiming to prevent a chronic elevation of blood Phe concentrations, which together with reduced tyrosine concentrations may increase the risk of neurologic damage. More recently, a sub-group of patients with PKU may benefit from pharmacological treatment with sapropterin, a chaperone for PAH, allowing increased tolerance to phenylalanine and protein intake. Although early reports have shown important nutritional status deficits probably due to the severe natural protein restriction, current studies with diet treatment only demonstrate less biochemical deficiency. Even so, despite a more favorable nutritional status impact in terms of growth and body composition, there is still a need to strictly monitor nutritional intake and nutritional status of these patients.


Objectives

    1. To describe nutritional status in treated patients with PKU, from Centro Hospitalar do Porto, during the period from 2009 until 2018.
    2. To analyze the longitudinal impact of exclusive dietary treatment in patients with PKU during the period between 2009 and 2014, just before sapropterin treatment start.
    3. To analyze the impact of sapropterin treatment on nutritional status in patients with PKU during the period between 2015 and 2018.
    4. To compare the nutritional status in patients under sapropterin treatment with patients under exclusive dietary treatment, in a parallel controlled study, during the period between 2015 and 2018.


Publications

Pinto A, et al. Nutritional status in patients with phenylketonuria using glycomacropeptide as their major protein source. European Journal of Clinical Nutrition (2017) 71(10):1230-1234.

Sousa Barbosa C, et al. Metabolic control in patients with phenylketonuria pre- and post-sapropterin loading test. Journal of Inborn Errors of Metabolism and Screening (2018) 6: 1–6.

Pinto A, et al. Over Restriction of Dietary Protein Allowance: The Importance of Ongoing Reassessment of Natural Protein Tolerance in Phenylketonuria. Nutrients (2019) 11(5):995.

Pena MJ, et al. Continuous use of glycomacropeptide in the nutritional management of patients with phenylketonuria: a clinical perspective. Orphanet Journal of Rare Diseases (2021) 16(1):84.

Peres M, et al. Implementing a Transition Program from Paediatric to Adult Services in Phenylketonuria: Results After Two Years of Follow-Up with an Adult Team. Nutrients (2021) 13(3):799.

  • Trends in nutritional status of patients with phenylketonuria (TNSPKU)
  • Metabolic control in patients with phenylketonuria under follow-up at Centro Hospitalar do Porto: a 2017 audit
  • Does phenylalanine restricted diet impacts microbiota in patients with phenylketonuria?
  • Is the phenylalanine-restricted diet a risk factor for overweight and obesity in patients with phenylketonuria (pku)? A systematic review and meta-analysis.
  • Biochemical and anthropometric outcomes of paediatric patients with heterozygous familial hypercholesterolemia after COVID-19 pandemic lockdowns

Rocha JC, et al. Molecular Genetics and Metabolism (2012) 107(4):659-63. 

Adam S, et al. Dietary management of urea cycle disorders: European practice. Molecular Genetics and Metabolism (2013) 110(4):439-45.

Adam S, et al. Molecular Genetics and Metabolism (2013) 110(4):454-59.

Pena MJ, et al. Orphanet Journal of Rare Diseases (2015) 10(1):162.

Rocha JC, et al. Annals of Nutrition & Metabolism (2016) 68(1):60-5.

Pena MJ, et al. European Journal of Clinical Nutrition (2016) 70(7):785-9.

Pinto A, et al. Molecular Genetics and Metabolism Reports (2017) 12:16–22.

Pinto A, et al. European Journal of Clinical Nutrition (2017) 71(10):1230-1234.

Daly A, et al. Molecular Genetics and Metabolism Reports (2017) 13:83-89.

Pinto A, et al. Orphanet Journal of Rare Diseases (2018) 13(1):21.

MacDonald A, et al. Nutrition Research Reviews (2018) 32(1):70-78.  

Pena MJ, et al. Nutrients (2018) 10(11):1794. 

Pinto A, et al. Molecular Genetics and Metabolism Reports (2018) 18:39-44.

Daly A, et al. Orphanet Journal of Rare Diseases (2019) 14(1):44.

Daly A, et al. Nutrients (2019) 11(3):520.

Pena MJ, et al. Journal of Cellular Biochemistry (2019) 120 (8), 13056-13065.

Pinto A, et al. Nutrients (2019) 11(5):995.

Rocha JC, et al. Journal of Pediatric Endocrinology and Metabolism (2019) 32(6):635-641.

Ilgaz F, et al. Nutrients (2019) 11(9):2070.

Pinto A, et al. Journal of Pediatric Endocrinology and Metabolism (2020) 33(1):147-155.

Cannet C, et al. 
Orphanet Journal of Rare Diseases (2020) 15(1):61.

Rocha JC, et al. American Journal of Physiology Endocrinology Metabolism (2020) 318(6):E890-E891. 

Wood G, et al. Nutrients (2020) 12(6):1893. 

MacDonald A, et al. Orphanet Journal of Rare Diseases (2020) 15(1):171. 

Daly A, et al. Nutrients (2020) 12(8):2443. 

Daly A, et al. Nutrients (2020) 12(9):2704. 

Daly A, et al. Nutrients (2020) 12(10):3153. 

Kraleva D, et al. Nutrients (2020) 12(11):3440. 

Pena MJ, et al. Orphanet Journal of Rare Diseases (2021) 16(1):84. 

Evers RAF, et al. Molecular Genetics and Metabolism (2021) 132(4):215-219.

Peres M, et al. Nutrients (2021) 13(3):799.

Daly A, et al. Nutrients (2021) 13(4):1323. 

Rocha JC, et al. Molecular Genetics and Metabolism Reports (2021) 28:100771. 

Daly A, et al. Nutrients (2021) 13(6):2075.

  • 2016 - Sollari Allegro Prize - Original Scientific Paper published in 2015 - Honorable Mention. Publication:  Pena MJ, Almeida MF, van Dam E, Ahring K, Bélanger-Quintana A, Dokoupil K, Gokmen-Ozel H, Lammardo AM, MacDonald A, Robert M, Rocha JC. Special low protein foods for phenylketonuria: availability in Europe and an examination of their nutritional profile. Orphanet Journal of Rare Diseases (2015):10(1):162.
  • 2020 - Portuguese Society of Metabolic Disorders / Recordati Rare Diseases research grant
    Title: Does phenylalanine restricted diet impacts microbiota in patients with phenylketonuria?
    Catarina Rodrigues
  • Dr.ª Ana Cristina Ferreira; Reference Centre of Inherited Metabolic Diseases, Centro Hospitalar Universitário de Lisboa Central
  • Alex Pinto, Dr. Anne Daly, Professor Anita MacDonald; Birmingham Children’s Hospital, Birmingham, UK

Principal Investigator

Júlio César Rocha

Team

André Rosário
Ana Faria
Catarina Rodrigues
MSc Student