Maria Teresa Carbone
Ospedale SS Annunziata, UOC Pediatrics, Naples, Italy
Phenylketonuria (PKU), or hyperphenylalaninemia (HPA), is the most common hereditary amino acid metabolic disorder (Online Mendelian Inheritance in Man database 261600) [Scriver et al, 2010]. It is an autosomal recessive disease which, in 98% of cases, is linked to mutations of the phenylalanine hydroxylase gene (PAH) and, in 1–2% of cases, a deficit in the synthesis or regeneration of the cofactor tetrahydrobiopterin (BH4). The PAH gene encodes the hepatic expression of an enzyme which catalyses the conversion of phenylalanine (Phe) into tyrosine (Tyr). Elevated Phe plasma levels cause cerebral damage if the PKU is not promptly diagnosed and treated [Scriver et al, 2010].
The Dr. Schär R&D Centre is the research and development department of Dr. Schär, that has been located in the AREA Science Park at Padriciano (Trieste) since 2003 – one of the leading multi-sectoral science and technology parks on an international level. The team is made up of 17 researchers – mostly graduates in Food Science and Technology – and is directed by Dr Virna Cerne, who has led the company's R&D department since 1996. The researchers at the Dr. Schär R&D Centre follow all the research and development activities for the entire Dr. Schär group: from researching innovative raw materials, new formulations and new technologies, to improving product ranges and developing new ideas which are then produced in the group's various factories in Italy, Germany, Spain, the USA and Austria, or by contractors.
Correa Garzón Luz N (1), Muñoz Gil Natalia M (2), Gómez Juan Fernando (3)
1. Pediatric Neurologist, Metabolic Therapies Bogotá Colombia, 2. Pediatric -Nutritionist, Metabolic Therapies. Bogotá Colombia,
3. Pediatric Neurologist Fundación Valle de LilI, Cali Colombia.
Epilepsies in the neonatal period could be caused by inborn errors of metabolism; they are rare diseases, usually with intractable epileptic seizures. Some of these epilepsies have a specific treatment, like epilepsies that respond to vitamins or to the cerebral glucose transporter deficiency Glut 1.
We reported the case of a patient with deficiency of glut 1 and intractable epilepsy, treated with ketogenic diet that achieves complete control of the epileptic seizures.
Birmingham Children’s Hospital, Birmingham, UK
The primary treatment for children with Phenylketonuria (PKU) is a low phenylalanine (phe) diet supplemented with phe-free L-amino acids. Children diagnosed by newborn screening are exposed to the bitter flavours of L-amino acid supplements usually within the first 2 weeks of life. Adherence with these supplements throughout infancy and childhood is essential for maintenance of good metabolic control. It is unknown if this early exposure to bitter flavours results in taste imprinting that subsequently leads to a preference and improved acceptance of other bitter foods during the weaning years and childhood. Certainly, studies in children exposed to bitter-tasting protein hydrolysate formula from an early age, show a stronger preference for bitter, sour and savoury tasting foods than do children raised on standard cow’s milk formula or breast milk [Menella et al, 2002, 2006, 2009, 2011; Beauchamp et al, 2009, 2011]. There is also evidence that these early experiences can influence food preferences in early childhood [Menella et al, 2002, 2006; Beauchamp et al, 2009, 2011].
Júlio César Rocha
Centro de Genética Médica JM, CHP EPE, Porto, Portugal
Faculdade de Ciências da Saúde, UFP, Porto, Portugal
Center Health Technology Services Research (CINTESIS), Porto, Portugal
Phenylketonuria (PKU; MIM 261600) is an inborn error of amino acid metabolism caused by reduced phenylalanine hydroxylase (PAH; EC 220.127.116.11) activity (Blau et al 2010). After the discover by Dr. Asbjørn Følling (Folling 1994), the first treatment approach was proposed by Dr. Horst Bickel in 1950s (Bickel et al 1953). Despite new therapies have recently emerged [large neutral amino acids (LNAA), Glycomacropeptide (GMP) and Sapropterin (BH4)] (Ney et al 2014), the proposed dietary phenylalanine (Phe) restriction is still the mainstay of treatment for patients with PKU. This is achieved through a natural protein restricted diet giving simultaneously a Phe-free amino acid mixture (protein substitute), nowadays enriched with vitamins and minerals (Giovannini et al 2012). In order to satisfy patient’s energy needs and to improve dietary compliance, special low protein foods are currently available for inclusion in the diet. The nutritional composition of these foods reveals a significant richness in carbohydrates and fat, while protein and Phe content are almost negligible (Rocha et al 2007).
Michael Staudigl (physician), Katharina Dokoupil (nutritionist), Esther M. Maier (physician, head of department)
Dr. von Hauner Children’s Hospital, Department of Inborn Errors of Metabolism, University of Munich, Munich, Germany
Phenylalanine hydroxylase (PAH; EC 18.104.22.168) catalyzes the hydroxylation of the aromatic amino acid phenylalanine to tyrosine. Mutations in the PAH gene lead to the most common inherited disorder of amino acid metabolism in the European-descended population, namely Phenylketonuria (PKU; OMIM 261600) (Zschocke, 2003). PAH deficiency leads to an elevation of phenylalanine concentrations in blood resulting in severely impaired cognitive and motor development if untreated. The implementation of newborn screening in the 1960s has helped to identify newborns with PKU within the first days of life and allowed early initiation of treatment to prevent these deleterious effects. For over 60 years, the mainstay of PKU treatment has been a phenylalanine-restricted diet. Yet, with ongoing research, new therapeutic options have emerged. We provide a short overview of current and future treatment options for PKU patients and the future role of dietary treatment.