- Email: [email protected]
Consensus on the guidelines for the dietary management of classical galactosemia
Clinical Nutrition ESPEN 10 (2015) e1ee4
Contents lists available at ScienceDirect
Clinical Nutrition ESPEN journal homepage: http://www.clinicalnutritionespen.com
Short report
Consensus on the guidelines for the dietary management of classical galactosemia Kristel Vande Kerckhove a, *, Marianne Diels a, Sigrid Vanhaesebrouck a, Karin Luyten b, Nancy Pyck b, An De Meyer b, Marleen Van Driessche c, Martine Robert d, Karen Corthouts e, Ariane Caris f, Emilie Duchateau g, Martine Dassy h, Genevieve Bihet i a
Inherited Metabolic Disease Center, University Hospital Leuven, Leuven, Belgium Inherited Metabolic Disease Center, University Hospital Antwerpen, Antwerp, Belgium Inherited Metabolic Disease Center, University Hospital Gent, Gent, Belgium d Inherited Metabolic Disease Center, Children's Hospital, Brussels, Belgium e Inherited Metabolic Disease Center, University Hospital Brussel, Brussels, Belgium f Service de G en etique Humaine, CHU Sart Tilman Li ege, Li ege, Belgium g Institute de Pathologie et de G en etique, Gosselies, Belgium h Cliniques Universitaires Saint- Luc Bruxelles -Woluwe, Brussels, Belgium i Clinique de l’Esp erance, Montegn ee, Belgium b c
a r t i c l e i n f o
s u m m a r y
Article history: Received 30 April 2014 Accepted 22 October 2014
Background and aim: Worldwide there is scientific discussion about the dietary management of galactosemia. The dietary management is very different in several countries among Europe, the US and Canada. The main points of discussion are related to the fact that i) despite a strict diet some patients still have poor outcomes; ii) there is lack of scientific knowledge about the role of endogenous production of galactose on disease evolution, with or without diet. The aim of the current work was the creation of a Belgian consensus on dietary guidelines for the management of galactosemia. Methods: A step-wise approach was used to achieve a consensus, including: a workshop, a Delphi round, discussion groups and a round table of different Belgian experts. Results: The consensus is an agreement between strict guidelines (strict limitation of fruits, vegetables and soybean products/French guidelines) and the more liberal guidelines (comparable with a diet free of lactose/guidelines of UK and the Netherlands). The consensus document consists of different modules, including the medical context, the theoretical background of dietary guidelines and the age-specific practical dietary guidelines. Conclusion: A Belgian consensus on the guidelines for the dietary management of classical galactosemia was developed despite the uncertainties of the efficacy and practical application of these guidelines. The final consensus is based on scientific knowledge and practical agreement among experts. In the future, regular revision of the guidelines is recommended and a uniform European guideline is desirable. © 2014 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.
Keywords: Galactosemia Diet therapy Management Dietary carbohydrates Medical nutrition therapy
1. Introduction Galactosemia is an inherited disorder of galactose metabolism that results from a defect in one of the following enzymes: galactokinase (GALK), GAL-1-phospate uridyltransferase (GALT) and uridine diphosphate-GAL-4-epimerase (GALE). The most common form of galactosemia results from a defect in the GALT activity. Its
* Corresponding author. Clinical Nutrition Unit and Inherited Metabolic Disease Center, UZ Leuven, Herestraat 49, B-3000 Leuven, Belgium. Tel.: þ32 16341096. E-mail address: [email protected] (K.V. Kerckhove).
estimated incidence is 1/40,000e60,000 live births [1]. This form is called the classical galactosemia. Patients with GALT deficiency appear normal at birth but soon develop severe hepatic, renal and gastro-intestinal manifestations which, if not treated, mostly lead to death [2]. Removal of dietary lactose and galactose is essential as this will prevent or decrease the severity of the initial metabolic crisis in the neonate. Worldwide there is a controversy about the dietary management for galactosemia. A comparative study of Mac Donald et al. shows that the dietary management in all the contributing countries is different [3].
http://dx.doi.org/10.1016/j.clnme.2014.10.001 2212-8263/© 2014 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.
e2
K.V. Kerckhove et al. / Clinical Nutrition ESPEN 10 (2015) e1ee4
Meanwhile several European countries developed their own specific dietary management. The United Kingdom published, in 1999, its consensus on dietary guidelines for galactosemia [4]. Other countries published their guidelines later, e.g. the Netherlands in 2005 [5] and France in 2008 [6]. Each national guideline has different opinions on several points (e.g. acceptance of soy-based products, all vegetables allowed or not). This diversity of management plans has been confirmed in a recent publication of Jumbo-Lucioni et al. [7]. The main reasons for variation in dietary guidelines are: i) despite a strict diet, some patients still have poor outcomes. They still develop symptoms of learning difficulties, speaking problems or difficulties in language understanding and movement disorders. Despite strict diet adherence, girls with galactosemia can develop late or no onset of puberty. Patients with galactosemia mostly have fertility problems [8e11]; ii) there is a lack of scientific knowledge about the role of endogenous production of galactose on disease evolution, with or without diet. Endogenous production of galactose is not affected by the exogenous intake from the diet. But galactose tolerance increases with age partly as a result of the agerelated decrease of endogenous galactose production. The endogenous production of galactose in adult patients can reach 1000 mg/ day while the daily intake of galactose varies between 30 mg and 54 mg, depending on the type of diet [8e10]. Until recently, there was no consensus on the guidelines for dietary management of classical galactosemia in Belgium. The aim of the Belgian metabolic dietitians' workgroup was to develop a Belgian consensus on dietary guidelines for the management of galactosamia. This was an unique process as Belgium has a Dutch speaking and a French speaking community, both having their own specific lifestyle characteristics. 2. Material and methods Based on the known dietary guidelines worldwide and the different opinions of several countries, the Belgian Inherited Metabolic Disease Centers started to create a national consensus in May 2010. The process took two years. The process consisted of different consecutive steps: a workshop, a Delphi round (requiring up to date knowledge), discussion groups and an expert roundtable were organized. In Fig. 1 a schematic overview of the process is presented. In the first step, the opinions of the neighboring countries, the Netherlands and France, were presented in parallel with a selected number of other points of view from other countries. The aim of the seminar was to provide all the Belgian experts enough background about common practice in the neighboring countries. This seminar was followed by a roundtable of different Belgian experts (metabolic dietitians and medical doctors, working in the Belgian Inherited Metabolic Disease Centers). A consensus for the different points of discussion was aimed for. The different points of discussion (need for age-specific dietary differences; diet lactose-free or a galactose restricted diet; allowance of soy or not; the use of elemental formula; limitations regarding fruits and vegetables; which cheeses are allowed; allowance of eggs and organ meats; allowance of nuts, seeds and chocolate) were defined upfront, using the results of the seminar, comparing the galactose content of different foods in specialized food composition tables [12] and an extensive literature review available to all participants. The different discussions and related general decisions were summarized by the two coordinating dietitians in a first Belgian document. In the next phase a Delphi round was started. The first consensus document was sent out to all (n ¼ 13) members of the expert group. New literature and discussions between metabolic
Fig. 1. Decision making process and graphical presentation of used methodology.
experts (doctors and dietitians) led to further adaptations of the document. These adaptations were included in a second version of the document. The second version of the consensus document was discussed in a new round table of all Belgian metabolic dietitians, resulting in a third document. This version was finally sent out to all members of the expert group. All remarks were summarized by the two coordinating dietitians in a final document. On the annual meeting of Belgian metabolic experts “Metabolics.be”, May 2011, “The Dutch version of the Belgian consensus” was presented. In a last step the consensus was translated into French. 3. Results & discussion Knowing the current ambiguity of the dietary management of galactosamia regarding the optimal strictness and duration of dietary galactose restriction and the need for evidence-based best
K.V. Kerckhove et al. / Clinical Nutrition ESPEN 10 (2015) e1ee4 Table 1 Description of the different groups (Belgian consensus on dietary guidelines for the management of galactosamia). Type
Description
Eat freely
Free of or low galactose. Foods in this section are free to eat for all Food with a galactose content known to be low-moderate from Food Composition Databases or food with an unknown but suspected to be low-moderate galactose content. Foods in this section can be eaten after the toddler period These foods contain lactose, a source of galactose; Foods in this section cannot be eaten unless it is allowed by your metabolic doctor or dietitian
Eat only in small amounts
Prohibited
practice guidelines independently of the country of origin, Belgium needed specific guidelines. Before the creation of the Belgian consensus on dietary guidelines for management of galactosamia, the French speaking part of Belgium followed the guidelines from France and the Dutch speaking dietitians followed the guidelines from the Netherlands and UK. Reaching a consensus between the Dutch and French speaking dietitians therefore was a challenge but necessary as some patients are bilingual but treated in both communities but deserve the same advice, to avoid confusion for the patients. On the use of elemental formula in the first months of life, no consensus could be achieved. Therefore, it was agreed that every Belgian center has to decide for themselves on that point. The consensus document contains three modules which reflects i) the medical context of galactosamia, ii) theoretical background of the final dietary guidelines and practical details of the final dietary guidelines, iii) educational material regarding general nutritional knowledge (the last module). In the first module of the guidelines the three different metabolic disorders in the pathway of galactose and their symptoms are described in detail.
e3
The second module is divided into different chapters. In the first chapter an overview of the different food sources of galactose is provided, followed by an explanation of the importance of the endogenous galactose production and its influence on disease evolution. The second chapter of this module provides information about the principles of a low galactose diet. The third chapter gives an overview of all foods, according to the different food groups of the Flemish Food-Based Dietary Guidelines [13] or the French food pyramid [14], and their allowance in this specific diet. Therefore, all food items were divided into specific groups, designated as “eat freely”, “eat only in small amounts” and “prohibited”. Because of the huge variety of the galactose content of different foods in different food composition databases, it was decided to create groups without a specific breakdown but rather a general range. This decision is in line with the French guidelines. Table 1 provides an overview of the descriptors used. Because galactose tolerance increases with age, the diet is agespecific. The diet in different life stages is described in the next chapter of the second module of the guidelines. The younger the child, the more dietary restrictions are introduced, especially for fruits, vegetables, cheese [15] and soybean products. Table 2 provides an overview of the age-specific diet restrictions. All products that were prohibited for babies and toddlers have been added as there was discussion about the intestinal availability of galactose upon consumption of these products. Soybean products have been prohibited in babies and toddlers because of the potential risk of infertility, as shown in a study in sheep [16]. Nevertheless there was a lot of discussion about this topic. The final consensus of the dietary guidelines is a balance between the more strict French guidelines (strict limitation of fruits, vegetables and soybean products) [6] and the more liberal advice as found in the guidelines of the UK and the Netherlands (comparable with a lactose-free diet) [5].
Table 2 Age-specific differences in the diet (Belgian consensus on dietary guidelines for the management of galactosamia).
e4
K.V. Kerckhove et al. / Clinical Nutrition ESPEN 10 (2015) e1ee4
The last module of the consensus provides educational material regarding general nutritional knowledge. The first component consists of information about the interpretation of food labels. The second education component aims to increase the knowledge base about food ingredients and their relative content of galactose. Together with the guidelines a list of allowed brand products is also provided. This lists needs to be adapted every year. 4. Conclusion Despite the uncertainties of the efficacy of the diet, with regard to the outcome of the patient and despite the debate on the practical application of the diet between the different experts of the group, those Belgian metabolic doctors and dietitians, involved in the guidelines, indicated their strong support. The consensus is now the main guideline document for all Belgian metabolic dietitians working in the different Belgian Inherited Metabolic Disease Centers. The Belgian 2011 guidelines are an agreement between the different consensuses of several countries worldwide and based on the literature and advice of different experts. Further scientific research will lead to a better understanding of the degree of dietary restriction required for patients of different ages with classical galactosamia, which will hopefully result in evidence-based best practice guidelines, making adaptations to the current guidelines necessary. Author contributions Kristel Vande Kerckhove has drafted the paper and finalised the manuscript. All other authors contributed equally in the development of the consensus and the manuscript. All authors read and approved the final manuscript. Conflict of interest statement The authors declare that they have no conflict of interest. Acknowledgments We acknowledge Profs. D. Cassiman and C. Matthys (University Hospital Leuven, Belgium) for their professional contribution as reviewers and for the scientific support in the creation of the paper. A special word of appreciation goes to Dr. AM Bosch (Emma
Children's Hospital AMC, Netherlands), Dr. E Rubio (Academisch Ziekenhuis, Maastricht, Netherlands) and Dr. D. Dobbelaere ^ pital Jeanne de Flandre, Lille, France) for their input and point of (Ho view from the Netherlands and France. Finally, we also would like to thank the metabolic specialists from all contributing Belgian Inherited Metabolic Disease Centers for their contribution to this consensus. The full Dutch and French text versions of the Belgian Guidelines are available at http://tinyurl.com/mu5qhvn (Dutch version) or http://tinyurl.com/n6m86qv (French version) or at the websites of the different Inherited Metabolic Disease Centers of Belgium.
References [1] Saudubray J, Van den Berghe G, Walter J. Inborn metabolic diseases. 5 ed. Berlin, Germany: Springer; 2012. [2] Berry G, Walter J. Disorders of galactose metabolism. In: Saudubray J, Van den Berghe G, Walter J, editors. Inborn metabolic diseases, diagnosis and treatment. 5th ed. Springer; 2012. p. 141e9. [3] McDonald A, Portnoi P. Galactosemia: one diet for Europe? A compilation of papers from the sixth international dietitians meeting. In: Proceedings of the Society for Study of Inborn Errors and Metabolism; 2001. p. 24e8. [4] Walter JH, Collins JE, Leonard JV. Recommendations for the management of galactosaemia. UK Galactosaemia Steering Group. Arch Dis Child 1999;80: 93e6. €tisten Overleg Academische Ziekenhuizen. Dieetboekje, het dieet bij [5] Kinderdie €tisten Overleg Academische Ziekehuizen; 2005. galactosemie. Kinderdie miques de France. Guide de l'alimentation [6] Association des familles galactose mie. Association des familles galdes patients atteints de galactose miques de France; 2008. actose [7] Jumbo-Lucioni PP, Garber K, Kiel J, Baric I, Berry GT, Bosch A, et al. Diversity of approaches to classic galactosemia around the world: a comparison of diagnosis, intervention, and outcomes. J Inherit Metab Dis 2012;35:1037e49. [8] Bosch AM, Bakker HD, Wenniger-Prick LJ, Wanders RJ, Wijburg FA. High tolerance for oral galactose in classical galactosaemia: dietary implications. Arch Dis Child 2004;89:1034e6. [9] Bosch AM. Classical galactosaemia revisited. J Inherit Metab Dis 2006;29: 516e25. [10] Bosch AM. Classic galactosemia: dietary dilemmas. J Inherit Metab Dis 2011;34:257e60. [11] Rubio-Gozalbo ME, Gubbels CS, Bakker JA, Menheere PPCA, Wodzig WKWH, Land JA. Gonadal function in male and female patients with classic galactosemia. Hum Reprod Update 2010;16:177e88. [12] Souci Fachmann Kraut e food composition and nutrition tables. 6 ed. Stuttgart: Bundesministeriums f Verbraucherschutz, Ernrung und Landwirtschaft sowie der Lder; 2005. [13] Vanhauwaert E. De actieve voedingsdriehoek. Leuven: Acco; 2012. [14] Karott S. L'Institute Paul Lambin. Pyramide alimentaire. Brussels: Karott; 2011. [15] Portnoi PA, MacDonald A. Determination of the lactose and galactose content of cheese for use in the galactosaemia diet. J Hum Nutr Diet 2009;22:400e8. [16] Bennetts H, Underwood E, Shier F. A specific breeding problem of sheep on subterranean clover pastures in Western Australia. Aust Vet J 1946;22:2e12.
Contents lists available at ScienceDirect
Clinical Nutrition ESPEN journal homepage: http://www.clinicalnutritionespen.com
Short report
Consensus on the guidelines for the dietary management of classical galactosemia Kristel Vande Kerckhove a, *, Marianne Diels a, Sigrid Vanhaesebrouck a, Karin Luyten b, Nancy Pyck b, An De Meyer b, Marleen Van Driessche c, Martine Robert d, Karen Corthouts e, Ariane Caris f, Emilie Duchateau g, Martine Dassy h, Genevieve Bihet i a
Inherited Metabolic Disease Center, University Hospital Leuven, Leuven, Belgium Inherited Metabolic Disease Center, University Hospital Antwerpen, Antwerp, Belgium Inherited Metabolic Disease Center, University Hospital Gent, Gent, Belgium d Inherited Metabolic Disease Center, Children's Hospital, Brussels, Belgium e Inherited Metabolic Disease Center, University Hospital Brussel, Brussels, Belgium f Service de G en etique Humaine, CHU Sart Tilman Li ege, Li ege, Belgium g Institute de Pathologie et de G en etique, Gosselies, Belgium h Cliniques Universitaires Saint- Luc Bruxelles -Woluwe, Brussels, Belgium i Clinique de l’Esp erance, Montegn ee, Belgium b c
a r t i c l e i n f o
s u m m a r y
Article history: Received 30 April 2014 Accepted 22 October 2014
Background and aim: Worldwide there is scientific discussion about the dietary management of galactosemia. The dietary management is very different in several countries among Europe, the US and Canada. The main points of discussion are related to the fact that i) despite a strict diet some patients still have poor outcomes; ii) there is lack of scientific knowledge about the role of endogenous production of galactose on disease evolution, with or without diet. The aim of the current work was the creation of a Belgian consensus on dietary guidelines for the management of galactosemia. Methods: A step-wise approach was used to achieve a consensus, including: a workshop, a Delphi round, discussion groups and a round table of different Belgian experts. Results: The consensus is an agreement between strict guidelines (strict limitation of fruits, vegetables and soybean products/French guidelines) and the more liberal guidelines (comparable with a diet free of lactose/guidelines of UK and the Netherlands). The consensus document consists of different modules, including the medical context, the theoretical background of dietary guidelines and the age-specific practical dietary guidelines. Conclusion: A Belgian consensus on the guidelines for the dietary management of classical galactosemia was developed despite the uncertainties of the efficacy and practical application of these guidelines. The final consensus is based on scientific knowledge and practical agreement among experts. In the future, regular revision of the guidelines is recommended and a uniform European guideline is desirable. © 2014 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.
Keywords: Galactosemia Diet therapy Management Dietary carbohydrates Medical nutrition therapy
1. Introduction Galactosemia is an inherited disorder of galactose metabolism that results from a defect in one of the following enzymes: galactokinase (GALK), GAL-1-phospate uridyltransferase (GALT) and uridine diphosphate-GAL-4-epimerase (GALE). The most common form of galactosemia results from a defect in the GALT activity. Its
* Corresponding author. Clinical Nutrition Unit and Inherited Metabolic Disease Center, UZ Leuven, Herestraat 49, B-3000 Leuven, Belgium. Tel.: þ32 16341096. E-mail address: [email protected] (K.V. Kerckhove).
estimated incidence is 1/40,000e60,000 live births [1]. This form is called the classical galactosemia. Patients with GALT deficiency appear normal at birth but soon develop severe hepatic, renal and gastro-intestinal manifestations which, if not treated, mostly lead to death [2]. Removal of dietary lactose and galactose is essential as this will prevent or decrease the severity of the initial metabolic crisis in the neonate. Worldwide there is a controversy about the dietary management for galactosemia. A comparative study of Mac Donald et al. shows that the dietary management in all the contributing countries is different [3].
http://dx.doi.org/10.1016/j.clnme.2014.10.001 2212-8263/© 2014 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.
e2
K.V. Kerckhove et al. / Clinical Nutrition ESPEN 10 (2015) e1ee4
Meanwhile several European countries developed their own specific dietary management. The United Kingdom published, in 1999, its consensus on dietary guidelines for galactosemia [4]. Other countries published their guidelines later, e.g. the Netherlands in 2005 [5] and France in 2008 [6]. Each national guideline has different opinions on several points (e.g. acceptance of soy-based products, all vegetables allowed or not). This diversity of management plans has been confirmed in a recent publication of Jumbo-Lucioni et al. [7]. The main reasons for variation in dietary guidelines are: i) despite a strict diet, some patients still have poor outcomes. They still develop symptoms of learning difficulties, speaking problems or difficulties in language understanding and movement disorders. Despite strict diet adherence, girls with galactosemia can develop late or no onset of puberty. Patients with galactosemia mostly have fertility problems [8e11]; ii) there is a lack of scientific knowledge about the role of endogenous production of galactose on disease evolution, with or without diet. Endogenous production of galactose is not affected by the exogenous intake from the diet. But galactose tolerance increases with age partly as a result of the agerelated decrease of endogenous galactose production. The endogenous production of galactose in adult patients can reach 1000 mg/ day while the daily intake of galactose varies between 30 mg and 54 mg, depending on the type of diet [8e10]. Until recently, there was no consensus on the guidelines for dietary management of classical galactosemia in Belgium. The aim of the Belgian metabolic dietitians' workgroup was to develop a Belgian consensus on dietary guidelines for the management of galactosamia. This was an unique process as Belgium has a Dutch speaking and a French speaking community, both having their own specific lifestyle characteristics. 2. Material and methods Based on the known dietary guidelines worldwide and the different opinions of several countries, the Belgian Inherited Metabolic Disease Centers started to create a national consensus in May 2010. The process took two years. The process consisted of different consecutive steps: a workshop, a Delphi round (requiring up to date knowledge), discussion groups and an expert roundtable were organized. In Fig. 1 a schematic overview of the process is presented. In the first step, the opinions of the neighboring countries, the Netherlands and France, were presented in parallel with a selected number of other points of view from other countries. The aim of the seminar was to provide all the Belgian experts enough background about common practice in the neighboring countries. This seminar was followed by a roundtable of different Belgian experts (metabolic dietitians and medical doctors, working in the Belgian Inherited Metabolic Disease Centers). A consensus for the different points of discussion was aimed for. The different points of discussion (need for age-specific dietary differences; diet lactose-free or a galactose restricted diet; allowance of soy or not; the use of elemental formula; limitations regarding fruits and vegetables; which cheeses are allowed; allowance of eggs and organ meats; allowance of nuts, seeds and chocolate) were defined upfront, using the results of the seminar, comparing the galactose content of different foods in specialized food composition tables [12] and an extensive literature review available to all participants. The different discussions and related general decisions were summarized by the two coordinating dietitians in a first Belgian document. In the next phase a Delphi round was started. The first consensus document was sent out to all (n ¼ 13) members of the expert group. New literature and discussions between metabolic
Fig. 1. Decision making process and graphical presentation of used methodology.
experts (doctors and dietitians) led to further adaptations of the document. These adaptations were included in a second version of the document. The second version of the consensus document was discussed in a new round table of all Belgian metabolic dietitians, resulting in a third document. This version was finally sent out to all members of the expert group. All remarks were summarized by the two coordinating dietitians in a final document. On the annual meeting of Belgian metabolic experts “Metabolics.be”, May 2011, “The Dutch version of the Belgian consensus” was presented. In a last step the consensus was translated into French. 3. Results & discussion Knowing the current ambiguity of the dietary management of galactosamia regarding the optimal strictness and duration of dietary galactose restriction and the need for evidence-based best
K.V. Kerckhove et al. / Clinical Nutrition ESPEN 10 (2015) e1ee4 Table 1 Description of the different groups (Belgian consensus on dietary guidelines for the management of galactosamia). Type
Description
Eat freely
Free of or low galactose. Foods in this section are free to eat for all Food with a galactose content known to be low-moderate from Food Composition Databases or food with an unknown but suspected to be low-moderate galactose content. Foods in this section can be eaten after the toddler period These foods contain lactose, a source of galactose; Foods in this section cannot be eaten unless it is allowed by your metabolic doctor or dietitian
Eat only in small amounts
Prohibited
practice guidelines independently of the country of origin, Belgium needed specific guidelines. Before the creation of the Belgian consensus on dietary guidelines for management of galactosamia, the French speaking part of Belgium followed the guidelines from France and the Dutch speaking dietitians followed the guidelines from the Netherlands and UK. Reaching a consensus between the Dutch and French speaking dietitians therefore was a challenge but necessary as some patients are bilingual but treated in both communities but deserve the same advice, to avoid confusion for the patients. On the use of elemental formula in the first months of life, no consensus could be achieved. Therefore, it was agreed that every Belgian center has to decide for themselves on that point. The consensus document contains three modules which reflects i) the medical context of galactosamia, ii) theoretical background of the final dietary guidelines and practical details of the final dietary guidelines, iii) educational material regarding general nutritional knowledge (the last module). In the first module of the guidelines the three different metabolic disorders in the pathway of galactose and their symptoms are described in detail.
e3
The second module is divided into different chapters. In the first chapter an overview of the different food sources of galactose is provided, followed by an explanation of the importance of the endogenous galactose production and its influence on disease evolution. The second chapter of this module provides information about the principles of a low galactose diet. The third chapter gives an overview of all foods, according to the different food groups of the Flemish Food-Based Dietary Guidelines [13] or the French food pyramid [14], and their allowance in this specific diet. Therefore, all food items were divided into specific groups, designated as “eat freely”, “eat only in small amounts” and “prohibited”. Because of the huge variety of the galactose content of different foods in different food composition databases, it was decided to create groups without a specific breakdown but rather a general range. This decision is in line with the French guidelines. Table 1 provides an overview of the descriptors used. Because galactose tolerance increases with age, the diet is agespecific. The diet in different life stages is described in the next chapter of the second module of the guidelines. The younger the child, the more dietary restrictions are introduced, especially for fruits, vegetables, cheese [15] and soybean products. Table 2 provides an overview of the age-specific diet restrictions. All products that were prohibited for babies and toddlers have been added as there was discussion about the intestinal availability of galactose upon consumption of these products. Soybean products have been prohibited in babies and toddlers because of the potential risk of infertility, as shown in a study in sheep [16]. Nevertheless there was a lot of discussion about this topic. The final consensus of the dietary guidelines is a balance between the more strict French guidelines (strict limitation of fruits, vegetables and soybean products) [6] and the more liberal advice as found in the guidelines of the UK and the Netherlands (comparable with a lactose-free diet) [5].
Table 2 Age-specific differences in the diet (Belgian consensus on dietary guidelines for the management of galactosamia).
e4
K.V. Kerckhove et al. / Clinical Nutrition ESPEN 10 (2015) e1ee4
The last module of the consensus provides educational material regarding general nutritional knowledge. The first component consists of information about the interpretation of food labels. The second education component aims to increase the knowledge base about food ingredients and their relative content of galactose. Together with the guidelines a list of allowed brand products is also provided. This lists needs to be adapted every year. 4. Conclusion Despite the uncertainties of the efficacy of the diet, with regard to the outcome of the patient and despite the debate on the practical application of the diet between the different experts of the group, those Belgian metabolic doctors and dietitians, involved in the guidelines, indicated their strong support. The consensus is now the main guideline document for all Belgian metabolic dietitians working in the different Belgian Inherited Metabolic Disease Centers. The Belgian 2011 guidelines are an agreement between the different consensuses of several countries worldwide and based on the literature and advice of different experts. Further scientific research will lead to a better understanding of the degree of dietary restriction required for patients of different ages with classical galactosamia, which will hopefully result in evidence-based best practice guidelines, making adaptations to the current guidelines necessary. Author contributions Kristel Vande Kerckhove has drafted the paper and finalised the manuscript. All other authors contributed equally in the development of the consensus and the manuscript. All authors read and approved the final manuscript. Conflict of interest statement The authors declare that they have no conflict of interest. Acknowledgments We acknowledge Profs. D. Cassiman and C. Matthys (University Hospital Leuven, Belgium) for their professional contribution as reviewers and for the scientific support in the creation of the paper. A special word of appreciation goes to Dr. AM Bosch (Emma
Children's Hospital AMC, Netherlands), Dr. E Rubio (Academisch Ziekenhuis, Maastricht, Netherlands) and Dr. D. Dobbelaere ^ pital Jeanne de Flandre, Lille, France) for their input and point of (Ho view from the Netherlands and France. Finally, we also would like to thank the metabolic specialists from all contributing Belgian Inherited Metabolic Disease Centers for their contribution to this consensus. The full Dutch and French text versions of the Belgian Guidelines are available at http://tinyurl.com/mu5qhvn (Dutch version) or http://tinyurl.com/n6m86qv (French version) or at the websites of the different Inherited Metabolic Disease Centers of Belgium.
References [1] Saudubray J, Van den Berghe G, Walter J. Inborn metabolic diseases. 5 ed. Berlin, Germany: Springer; 2012. [2] Berry G, Walter J. Disorders of galactose metabolism. In: Saudubray J, Van den Berghe G, Walter J, editors. Inborn metabolic diseases, diagnosis and treatment. 5th ed. Springer; 2012. p. 141e9. [3] McDonald A, Portnoi P. Galactosemia: one diet for Europe? A compilation of papers from the sixth international dietitians meeting. In: Proceedings of the Society for Study of Inborn Errors and Metabolism; 2001. p. 24e8. [4] Walter JH, Collins JE, Leonard JV. Recommendations for the management of galactosaemia. UK Galactosaemia Steering Group. Arch Dis Child 1999;80: 93e6. €tisten Overleg Academische Ziekenhuizen. Dieetboekje, het dieet bij [5] Kinderdie €tisten Overleg Academische Ziekehuizen; 2005. galactosemie. Kinderdie miques de France. Guide de l'alimentation [6] Association des familles galactose mie. Association des familles galdes patients atteints de galactose miques de France; 2008. actose [7] Jumbo-Lucioni PP, Garber K, Kiel J, Baric I, Berry GT, Bosch A, et al. Diversity of approaches to classic galactosemia around the world: a comparison of diagnosis, intervention, and outcomes. J Inherit Metab Dis 2012;35:1037e49. [8] Bosch AM, Bakker HD, Wenniger-Prick LJ, Wanders RJ, Wijburg FA. High tolerance for oral galactose in classical galactosaemia: dietary implications. Arch Dis Child 2004;89:1034e6. [9] Bosch AM. Classical galactosaemia revisited. J Inherit Metab Dis 2006;29: 516e25. [10] Bosch AM. Classic galactosemia: dietary dilemmas. J Inherit Metab Dis 2011;34:257e60. [11] Rubio-Gozalbo ME, Gubbels CS, Bakker JA, Menheere PPCA, Wodzig WKWH, Land JA. Gonadal function in male and female patients with classic galactosemia. Hum Reprod Update 2010;16:177e88. [12] Souci Fachmann Kraut e food composition and nutrition tables. 6 ed. Stuttgart: Bundesministeriums f Verbraucherschutz, Ernrung und Landwirtschaft sowie der Lder; 2005. [13] Vanhauwaert E. De actieve voedingsdriehoek. Leuven: Acco; 2012. [14] Karott S. L'Institute Paul Lambin. Pyramide alimentaire. Brussels: Karott; 2011. [15] Portnoi PA, MacDonald A. Determination of the lactose and galactose content of cheese for use in the galactosaemia diet. J Hum Nutr Diet 2009;22:400e8. [16] Bennetts H, Underwood E, Shier F. A specific breeding problem of sheep on subterranean clover pastures in Western Australia. Aust Vet J 1946;22:2e12.