GLUTARIC ACIDURIA TYPE I A GUIDE FOR PARENTS AND PATIENTS CENTRE FOR PAEDIATRIC AND ADOLESCENT MEDICINE ANGELIKA-LAUTENSCHLÄGER CHILDREN'S HOSPITAL METABOLIC CENTRE UK HD Book-Open CONTENTS 4 | PREFACE AND OBJECTIVE OF THE GUIDE 6 | INTRODUCTION 6 Diagnosis 8 Natural disease course 10 Pathogenesis 12 Diet and carnitine 14 Emergency treatment 18 Treatment of movement disorders IMPRINT Publisher 20 | NUTRITION AND DIET Heidelberg University Hospital 20 Composition of our food 21 Food classification for the low-lysine diet Editors 23 Composition of the diet Dr. Nikolas Boy Prof. Dr. Stefan Kölker Katja Sahm 24 | PRINCIPLE OF DIETARY TREATMENT 26 Amino acid supplement Design and layout Corporate Communications of the Heidelberg University Hospital and Medical Faculty 28 | PRACTICAL APPLICATION OF THE DIET www.klinikum.uni-heidelberg.de/Unternehmenskommunikation 28 Diet for infants Eva Tuengerthal, graphics/layout 30 Food classification Photos photocase.com / Francesca Schellhaas / nonmim / b-fruchten / 34 | PATIENTS WITH MOVEMENT DISORDERS cw_design / Julia Straub / view7 / a_sto istockphoto.com 35 | EMERGENCY TREATMENT 35 Emergency dietary treatment at home Print Nino Druck GmbH, Heidelberg 36 | EXAMPLE DIETARY PLANS Translation Kindly supported by 40 | DIET AFTER THE AGE OF 6 YEARS 44 | FOOD COMPOSITION AND NUTRITION TABLE FOR CALCULATING THE LYSINE CONTENT Last updated 54 | BIBLIOGRAPHY November 2018 3 | 3 3 | 3 4 | 5 PREFACE AND OBJECTIVE CURRENT GUIDELINE FOR OF THE GUIDE GLUTARIC ACIDURIA TYPE I Your child (or you) has been diagnosed with glutaric aciduria type I. All recommendations given in this guide conform to the current guide- Dr. Nikolas Boy This diagnosis has certainly raised a number of questions and may line (AWMF Guideline No. 027/018, highest quality class “S3”, i.e. ev- Chairman of the Guideline Development Group since 2015 also have given rise to some concerns. You have probably neither idence- and consensus-based guideline) for the “Diagnosis, Therapy heard of this inherited metabolic disorder before, nor do you know and Management of Glutaric Aciduria Type I (synonym: glutaryl-CoA Prof. Dr. Stefan Kölker anyone else who has been diagnosed with this disease. Moreover, you dehydrogenase deficiency)”. The guideline was developed by an in- Head of the Division of Neuropaediatrics and Metabolic Medicine and may find it difficult to “understand” this disease, especially if your ternational guideline development group and published for the first Chairman of the Guideline Development Group 2003–2015 child (or you) does not show any apparent signs or symptoms. time in 2007. Besides Germany, the guideline also became a national therapy guideline in other countries (including Italy, Portugal and the Katja Sahm This 2nd updated edition of this guide is therefore directed primarily at Netherlands). Dietician parents and patients. It is designed to answer the most frequent ques- tions, give you a general idea of what glutaric aciduria type I is and The first revision of the guideline (2011) was based mainly on the re- how this disease is treated according to the present state of knowl- sults of a study on 52 patients who were identified by newborn screen- IN COLLABORATION WITH edge. Secondly, this guide is addressed to all professional groups that ing in Germany. This study was the first to demonstrate the positive provide treatment to children, adolescents and adults with glutaric effect of guideline-based treatment on the clinical outcome (Heringer Petra Schick aciduria type I. et al. 2010). This was taken as a basis for developing the 1st edition Dietitian of this guide for parents. Over the last few years, collaboration on a We hope that this guide will provide you with additional, hands-on national and international scale has made it possible to further expand Privatdozent Dr. Peter Burgard support during the daily treatment. However, this guide is in no way the knowledge on the disease and further increase the evidence level Head Psychologist intended to replace a structured initial consultation or the medical of the guideline recommendations. care and continuous training provided by the experienced team of a Prof. Dr., Prof. h.c. (RCH) Georg F. Hoffmann metabolic centre. Any change in the treatment should always be made In 2016, the guideline was revised for the second time, which forms Medical Director in consultation with the attending team of metabolic experts. the basis for this 2nd updated edition of the guide for parents. The current guideline still has the highest AWMF quality class “S3”. It con- Centre for Paediatric and Adolescent Medicine solidates the more than thirty years of experience of international Angelika-Lautenschläger Children's Hospital experts and meets the high requirements for objectivity, transparency, Department I evidence base and consensus development. In addition, the guideline Division of Neuropaediatrics and Metabolic Medicine takes into account additional criteria that are important for the treat- Metabolic Centre ment process, such as clinical relevance and experience, consistency Im Neuenheimer Feld 430 of evidence, benefits and risks for the patient, the perspective of the 69120 Heidelberg, Germany patient and the families, ethical, legal and economic aspects, the ap- plicability to the German health care system as well as practicability ENVELOPE in daily life. According to the present state of knowledge, the current [email protected] guideline recommendations are the most effective to best protect your [email protected] child's (or your) health and development. The complete guideline can [email protected] be obtained via the online portal of the Association of the Scientific Medical Societies in Germany (AWMF) (www.awmf.org/; main menu: P.S.: We will be happy to receive any suggestions for continuously “Guidelines”). It predominantly addresses all professional groups that improving the brochure. provide treatment to patients with glutaric aciduria type I. Even though the guideline and this guide have been prepared with the utmost care, they may contain inconsistencies or even mistakes. In ad- dition, not all patients may benefit fromProf. the Dr. recommended A. Unterberg treatment to the same extent. Therefore, no guaranteeÄrztlicher can be Direktorgiven as to the use of this guide and the therapeutic outcome. The practical implementa- tion of the recommended treatment and the associated duty of care are solely incumbent upon the attending physician. Kind regards, 5 | 5 6 | 7 GLUTARIC ACIDURIA TYPE I A GUIDE FOR PARENTS AND PATIENTS INTRODUCTION DIAGNOSIS Hand-point-right If there is a confirmed diagnosis of glutaric aciduria type I, other family members (in particular siblings and parents) of the affected patient should be specifically tested for the disease as well. WHAT DOES “GLUTARIC ACIDURIA TYPE I” MEAN? HOW IS THE DISEASE DIAGNOSED? tested for glutaric aciduria type I as part of the early detec- CAN OTHER FAMILY MEMBERS ALSO BE AFFECTED BY The term “glutaric aciduria” means “presence of glutaric Besides increased excretion of glutaric acid, glutaric ac- tion screening since 1 April 2005. On average, about 6–7 THE DISEASE? acid in the urine”. Glutaric acid is an intermediate break- iduria type I involves the presence of other substances in newborns are diagnosed with glutaric aciduria type I in Ger- Yes, this is possible. Since the disease is inherited, other down product of human metabolism. It is usually present the urine and other body fluids, such as 3-hydroxyglutaric many every year, which is equivalent to a prevalence of one close family members may be affected as well. This may in the body in small quantities only and is excreted in the acid and glutarylcarnitine. In people who are not affected newborn with glutaric aciduria type I in 120,000 newborns even be the case if no apparent symptoms are present in urine. Increased excretion of glutaric acid had already been by the disease, these substances are present in the body (1:120,000). them. observed in patients with glutaric aciduria before the ac- and blood in very small quantities only and are excreted in tual cause of the disease was discovered more than 40 the urine. These small quantities are also referred to as the To ultimately confirm the diagnosis, additional testing is years ago. This first-observed biochemical symptom gave “normal range” or “reference range”. In affected patients, necessary (molecular-genetic and, if necessary, enzymatic the disease its name. Since there are other diseases in- by contrast, these substances are present in increased con- testing). volving increased excretion of glutaric acid, these diseases centrations, which are often many times above the normal were classified into three types (type I, type II and type III). range. As a result, most affected children can already be This guide exclusively addresses glutaric aciduria type I. reliably identified by newborn screening. According to the Even though the names glutaric aciduria type II and type III German national guidelines for newborn screening (ww- sound very similar, they are different diseases, which must w.g-ba.de: Guidelines for children: Expanded newborn 7 | 7 not be confused with glutaric aciduria type I. screening), all newborns throughout Germany have been 8 | 9 GLUTARIC ACIDURIA TYPE I A GUIDE FOR PARENTS AND PATIENTS INTRODUCTION NATURAL DISEASE COURSE HOW DOES THE DISEASE MANIFEST? Adolescents and adults OTHER DISEASE FORMS By now, individual adolescents and adults with glutaric ac- In addition, there are individual patients who develop Newborns and young infants iduria type I have been identified who have come through insidious neurological symptoms without experiencing an Most newborns and young infants with glutaric aciduria childhood unscathed, despite not having been diagnosed acute crisis event (insidious-onset type). These patients are type I do not develop any symptoms and cannot be dis- and treated (“late-onset type”). The physical symptoms in usually affected by a milder form of dystonia than patients tinguished from healthy children of the same age.