RARE DISEASES SUBNETWORKS

Structure of the MetabERN Disease Coverage:
the MetabERN 7 subnetworks

Rationale

Aminoacid and organic acid diseases constitute the oldest group of inborn errors of metabolism. Some of them are universally adopted in the newborn screening and metabolic derangement can be prevented. Other disorders present as an overwhelming intoxication disorder leading to coma in a matter of hours. Some disorders are characterized by a peculiar smell or discoloration of the urine. These diseases are readily diagnosed in metabolic centers. In some specific diseases more targeted therapy with enzyme inhibitors or supplementation of specific vitamins can obviate the need for the complex diet. However, in most of these diseases a strict dietary therapy is necessary which often includes protein restriction. Large differences of available diet therapies exist between countries in the EU.

Objectives

The Aminoacid and organic acid Core Network within the MetabERN aims to:

    • gain an overview of patients with aminoacid and organic acid diseases in the EU (e.g. which diseases, how many patients, clinical outcome, etc.).
    • promote awareness towards aminoacid and organic acid diseases in the EU.
    • facilitate the more rapid diagnosis of aminoacid and organic acid diseases in the EU as often a significant diagnostic delay is still present.
    • improve and standardize management of aminoacid and organic acid diseases in the EU.
    • improve prospects of patients with aminoacid and organic acid disease in the EU by initiating and contributing to research and implementation of innovative therapies.

Organizational structure

The Aminoacid and organic acid Core Network will consist of participating HCPs within the MetabERN with expertise in the field of aminoacid and organic acid disorders and will build on or seek collaboration with existing international collaborations and networks of HCPs in the field of aminoacid and organic acid disorders. Working groups will be formed to address different important topics within the field of aminoacid and organic acid diseases.

These include:

  • Prevention & Screening for aminoacid and organic acid disorders (including newborn screening).
  • Diagnosis of (new) aminoacid and organic acid disorders (including identification of biomarkers).
  • Management of aminoacid and organic acid disorders (development of clinical guidelines & care paths).
  • Epidemiology & Outcome (participation in existing and development of new registries).
  • Education and Training (development of E-learning tools, work-shops and courses).
  • Virtual Counselling (for specific diseases at different HCPs with specific expertise).
  • Patient Empowerment (organization of patient meetings and interaction with patient organizations).
  • Research (fundamental, translational, clinical).

The executive board of the Aminoacid and organic acid Core Network will be formed by the chairpersons of the working groups. An advisory board (with members of patients organizations, policy makers, etc) will be appointed to monitor the different activities of the Aminoacid and organic acid Core Network.

Amino and organic acids-related disorders

Coordinators

STEFAN KÖLKER, MD

Centre for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Germany

Henk Blom

Medical Center University of Freiburg

FRANCJAN VAN SPRONSEN

Full prof in Pediatrics UNIVERSITY OF GRONINGEN, UNIVERSITY MEDICAL CENTER GRONINGEN, BEATRIX CHILDRENS’HOSPITAL, SECTION OF METABOLIC DISEASES, GRONINGEN, THE NETHERLANDS

Rationale

Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism provides the essential fuel (ATP) for the functioning of the human cell. More than 300 genes are involved in normal mitochondrial function. The clinical presentation can be quite diverse ranging from eye disease to multisystem, neurologic and myopathic involvement. While this represents the most common inborn error in metabolism the severity can vary a lot from lethally affected newborns to monosymptomatic elderly. Diagnosis is certainly not straightforward as one mitochondrial disease can present with a multitude of symptoms and on the other hand, one symptom can be cause by many different mitochondrial diseases. Respiratory chain complexes (the important functional part of the mitochondrion) can be analyzed by a few highly specialized laboratories across Europe. Treatment is often lacking, although numerous clinical trials have been launched.

Objectives

The Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism Core Network within the MetabERN aims to:

    • gain an overview of patients with Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism diseases in the EU (e.g. which diseases, how many patients, clinical outcome, etc.).
    • promote awareness towards Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism diseases in the EU.
    • facilitate the more rapid diagnosis of Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism diseases in the EU as often a significant diagnostic delay is still present.
    • improve and standardize management of Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism diseases in the EU.
    • improve prospects of patients with Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism disease in the EU by initiating and contributing to research and implementation of innovative therapies.

Organizational structure

The Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism Core Network will consist of participating HCPs within the MetabERN with expertise in the field of Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism diseases and will build on or seek collaboration with existing international collaborations and networks of HCPs in the field of Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism diseases. Working groups will be formed to address different important topics within the field of Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism diseases.

These include:

  • Prevention & Screening for Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism diseases.
  • Diagnosis of (new) Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism diseases (including identification of biomarkers).
  • Management of Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism diseases (development of clinical guidelines & care paths).
  • Epidemiology & Outcome (participation in existing and development of new registries).
  • Education and Training (development of E-learning tools, work-shops and courses).
  • Virtual Counselling (for specific diseases at different HCPs with specific expertise).
  • Patient Empowerment (organization of patient meetings and interaction with patient organizations).
  • Research (fundamental, translational, clinical).

The executive board of the Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism Core Network will formed by the chairpersons of the working groups. An advisory board (with members of patients organizations, policy makers, etc) will be appointed to monitor the different activities of the Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism Core Network.

Pyruvate metabolism mitochondrial oxidative phosphorylation disorders, Krebs cycle defects, disorders of thiamine transport & metabolism

Coordinators

Enrico Bertini

Ospedale Pediatrico Bambino Gesù

Manuel Schiff

Assistance Publique Hôpitaux de Paris- University Hospital Robert-Debré

Shamina Rahman

UCL Great Ormond Street Institute of Child Health, London, UK

Rationale

Carbohydrate, fatty acid oxidation and ketone bodies diseases constitute a diverse group of inherited disorders playing a central role in the energy requirements of the cell. Most are characterized by hypoglycemia in relation to food intake. Hypoglycemia is one of the most common presentation of inborn errors of metabolism. Diagnostic work-up can be difficult and can require sampling at the time of a hypoglycemia. In some disorders cardiomyopathy or myopathy is a central feature. Dietary therapy and avoidance of fasting plays an important role in preventing morbidity.

Objectives

The Carbohydrate, fatty acid oxidation and ketone bodies Core Network within the MetabERN aims to:

    • gain an overview of patients with carbohydrate, fatty acid oxidation and ketone bodies disorders in the EU (e.g. which diseases, how many patients, clinical outcome, etc.).
    • promote awareness towards carbohydrate, fatty acid oxidation and ketone bodies diseases in the EU.
    • facilitate the more rapid diagnosis of carbohydrate, fatty acid oxidation and ketone bodies diseases in the EU as often a significant diagnostic delay is still present.
    • improve and standardize management of carbohydrate, fatty acid oxidation and ketone bodies diseases in the EU.
    • improve prospects of patients with carbohydrate, fatty acid oxidation and ketone bodies disease in the EU by initiating and contributing to research and implementation of innovative therapies.

Organizational structure

The Carbohydrate, fatty acid oxidation and ketone bodies Core Network will consist of participating HCPs within the MetabERN with expertise in the field of carbohydrate, fatty acid oxidation and ketone bodies diseases and will build on or seek collaboration with existing international collaborations and networks of HCPs in the field of carbohydrate, fatty acid oxidation and ketone bodies diseases. Working groups will be formed to address different important topics within the field of carbohydrate, fatty acid oxidation and ketone bodies diseases.

These include:

  • Prevention & Screening for carbohydrate, fatty acid oxidation and ketone bodies diseases.
  • Diagnosis of (new) carbohydrate, fatty acid oxidation and ketone bodies diseases (including identification of biomarkers).
  • Management of carbohydrate, fatty acid oxidation and ketone bodies diseases (development of clinical guidelines & care paths).
  • Epidemiology & Outcome (participation in existing and development of new registries).
  • Education and Training (development of E-learning tools, work-shops and courses).
  • Virtual Counselling (for specific diseases at different HCPs with specific expertise).
  • Patient Empowerment (organization of patient meetings and interaction with patient organizations).
  • Research (fundamental, translational, clinical).

The executive board of the Carbohydrate, fatty acid oxidation and ketone bodies Core Network will be formed by the chairpersons of the working groups. An advisory board (with members of patients organizations, policy makers, etc) will be appointed to monitor the different activities of the Carbohydrate, fatty acid oxidation and ketone bodies Core Network.

Carbohydrate, fatty acid oxidation and ketone bodies disorders

Coordinators

Carlo Dionisi Vici

Division of Metabolic Diseases, Department of Pediatric Medicine, Bambino Gesù Children’s Research Hospital, Rome, Italy

Ute SPIEKERKOETTER

Medical Director of the Department of Pediatrics, Adolescent Medicine and Neonatology at the University Children’s Hospital in Freiburg, Germany

Terry Derks

University of Groningen UMC Groningen, the Netherlands

Rationale

Lysosomal diseases constitute a group of over 50 inherited disorders in lysosomal metabolism.
Most have multi-organ involvement, all are progressive and many have neurodegenerative features.
Some can be treated, but for most only supportive care is available.
The combined incidence is estimated at 1 new case per 5.000-10.000 newborns per year, which results in approximately 500 to 1000 new patients with a lysosomal disease in the EU per year.
Diagnosis can be difficult as symptoms may slowly progress and highly specialized diagnostic tools are mandatory, often resulting in diagnostic delays. Large differences in awareness, availability of diagnostic tools and treatment options exist between countries in the EU.

Objectives

The Lysosomal Core Network within the MetabERN aims to:

    • gain an overview of patients with lysosomal diseases in the EU (e.g. which diseases, how many patients, clinical outcome, etc.).
    • promote awareness towards lysosomal diseases in the EU.
    • facilitate the more rapid diagnosis of lysosomal diseases in the EU as often a significant diagnostic delay is still present.
    • improve and standardize management of lysosomal diseases in the EU.
    • improve prospects of patients with lysosomal disease in the EU by initiating and contributing to research and implementation of innovative therapies.

Organizational structure

The Lysosomal Core Network will consist of participating HCPs within the MetabERN with expertise in the field of lysosomal diseases and will build on or seek collaboration with existing international collaborations and networks of HCPs in the field of lysosomal diseases. Working groups will be formed to address different important topics within the field of lysosomal diseases.

These include:

  • Prevention & Screening for lysosomal diseases.
  • Diagnosis of (new) lysosomal diseases (including identification of biomarkers).
  • Management of lysosomal diseases (development of clinical guidelines & care paths).
  • Epidemiology & Outcome (participation in existing and development of new registries).
  • Education and Training (development of E-learning tools, work-shops and courses).
  • Virtual Counselling (for specific diseases at different HCPs with specific expertise).
  • Patient Empowerment (organization of patient meetings and interaction with patient organizations).
  • Research (fundamental, translational, clinical).

The executive board of the Lysosomal Core Network will formed by the chairpersons of the working groups.
An advisory board (with members of patients organizations, policy makers, etc) will be appointed to monitor the different activities of the Lysosomal Core Network.

Lysosomal Storage disorders

Coordinators

Ans van der Ploeg

Center for Lysosomal and Metabolic Diseases, Erasmus MC University Hospital Rotterdam, The Netherlands

Dominique P. Germain

Hôpitaux Universitaires Paris Ile de France Ouest, France

Giancarlo Parenti

Azienda Ospedaliera Universitaria "Federico II", Napoli, Italy

Rationale

Peroxisomal diseases and lipid related disorders constitute a growing group of inborn errors of metabolism. There clinical presentation of peroxisomal disorders can be quite diverse ranging from neurological and behavioral disease to bone abnormalities. Some are progressive and many have neurodegenerative features. For most of these diseases, treatment is largely supportive. The incidence of peroxisomal disorders is estimated at 1 new case per 20.000 newborns per year. Diagnosis can be difficult as symptoms may slowly progress and highly specialized diagnostic tools are mandatory, often resulting in diagnostic delays. Large differences in awareness, availability of diagnostic tools and treatment options exist between countries in the EU.

The lipid related disorders are a diverse group of inborn errors of metabolism. They include lipid synthesis and transport defects, and one of the most frequent group of IMDs.

Objectives

The Peroxisomal and lipid related disorders Core Network within the MetabERN aims to:

    • gain an overview of patients with peroxisomal and lipid related diseases in the EU (e.g. which diseases, how many patients, clinical outcome, etc.).
    • promote awareness towards peroxisomal and lipid related diseases in the EU.
    • facilitate the more rapid diagnosis of peroxisomal and lipid related diseases in the EU as often a significant diagnostic delay is still present.
    • improve and standardize management of peroxisomal and lipid related diseases in the EU.
    • improve prospects of patients with peroxisomal and lipid related disease in the EU by initiating and contributing to research and implementation of innovative therapies.

Organizational structure

The Peroxisomal and lipid related Core Network will consist of participating HCPs within the MetabERN with expertise in the field of these diseases and will build on or seek collaboration with existing international collaborations and networks of HCPs in the field. Working groups will be formed to address different important topics within the field of peroxisomal and lipid diseases.

These include:

  • Prevention & Screening for peroxisomal and lipid diseases diseases.
  • Diagnosis of (new) peroxisomal and lipid diseases (including identification of biomarkers).
  • Management of peroxisomal and lipid diseases (development of clinical guidelines & care paths).
  • Epidemiology & Outcome (participation in existing and development of new registries).
  • Education and Training (development of E-learning tools, work-shops and courses).
  • Virtual Counselling (for specific diseases at different HCPs with specific expertise).
  • Patient Empowerment (organization of patient meetings and interaction with patient organizations).
  • Research (fundamental, translational, clinical).

The executive board of the Peroxisomal and lipid related Core Network will formed by the chairpersons of the working groups. An advisory board (with members of patients organizations, policy makers, etc) will be appointed to monitor the different activities of the Peroxisomal and lipid related Core Network.

Peroxisomal disorders

Coordinators

Bwee Tien Poll The

Pediatric Neurology Academic Medical Center Amsterdam, The Netherlands

Linda De Meirleir

Professor and Head of Pediatric Neurology and Metabolic Diseases,
Dept. of Pediatrics, Vrie Universiteit Brussels,
UZ Brussel
Laarbeeklaan 101
1090 Brussels
Belgium

François Eyskens

University Hospital of Antwerp, Center of Inherited Metabolic Diseases, Belgium

Rationale

Congenital disorders of glycosylation diseases constitute a group of over 100 inherited disorders and every year new disorders are being discovered. Many proteins in the human body are glycosylated to be able to fulfill their function. Glycosylated proteins play a role in multiple biologic processes, and participate in cellular trafficking. Disorders of glycosylation present often with multisystem diseases. For some of these disorders dietary therapy with simple sugars can lead to great clinical improvements. Supportive care is paramount and care strategies vary broadly in Europe.

Objectives

The Congenital disorders of glycosylation Core Network within the MetabERN aims to:

    • gain an overview of patients with congenital disorders of glycosylation diseases in the EU (e.g. which diseases, how many patients, clinical outcome, etc.).
    • promote awareness towards congenital disorders of glycosylation diseases in the EU.
    • facilitate the more rapid diagnosis of congenital disorders of glycosylation diseases in the EU as often a significant diagnostic delay is still present.
    • improve and standardize management of congenital disorders of glycosylation diseases in the EU.
    • improve prospects of patients with congenital disorders of glycosylation disease in the EU by initiating and contributing to research and implementation of innovative therapies.

Organizational structure

The Congenital disorders of glycosylation Core Network will consist of participating HCPs within the MetabERN with expertise in the field of congenital disorders of glycosylation diseases and will build on or seek collaboration with existing international collaborations and networks of HCPs in the field of congenital disorders of glycosylation diseases. Working groups will be formed to address different important topics within the field of congenital disorders of glycosylation diseases.

These include:

  • Prevention & Screening for congenital disorders of glycosylation diseases.
  • Diagnosis of (new) congenital disorders of glycosylation diseases (including identification of biomarkers).
  • Management of congenital disorders of glycosylation diseases (development of clinical guidelines & care paths).
  • Epidemiology & Outcome (participation in existing and development of new registries).
  • Education and Training (development of E-learning tools, work-shops and courses).
  • Virtual Counselling (for specific diseases at different HCPs with specific expertise).
  • Patient Empowerment (organization of patient meetings and interaction with patient organizations).
  • Research (fundamental, translational, clinical).

The executive board of the Congenital disorders of glycosylation Core Network will formed by the chairpersons of the working groups. An advisory board (with members of patients organizations, policy makers, etc) will be appointed to monitor the different activities of the Congenital disorders of glycosylation Core Network.

Congenital disorders of glycosylation and disorders of intracellular trafficking

Coordinators

Eva Morava

University Hospitals Leuven, Department of Pediatrics, Division of Metabolic Disorders

Tomáš Honzík

Charles University and General University Hospital in Prague, • Department of Pediatrics and Adolescent Medicine (1. LF)

Pascal De Lonlay

Hôpital Necker-Enfants Malades, APHP, University Paris-Descartes, France

Rationale

Neurotransmitter and small molecule disorders diseases are mainly characterized by a neurological picture often including movement disorders, epilepsy and developmental delay. Often invasive tests are required (for instance spinal fluid tap) to make the diagnosis and monitor therapy. Analysis of these samples are performed in a handful of specialized laboratories across Europe. Collaboration between neurologists and metabolic disease specialists is important to achieve optimal quality of live and symptom control. Vitamins can correct some of these disorders almost completely.

Objectives

The Neurotransmitter and small molecule disorders Core Network within the MetabERN aims to:

    • gain an overview of patients with neurotransmitter and small molecule disorders diseases in the EU (e.g. which diseases, how many patients, clinical outcome, etc.).
    • promote awareness towards neurotransmitter and small molecule disorders diseases in the EU.
    • facilitate the more rapid diagnosis of neurotransmitter and small molecule disorders diseases in the EU as often a significant diagnostic delay is still present.
    • improve and standardize management of neurotransmitter and small molecule disorders diseases in the EU.
    • improve prospects of patients with neurotransmitter and small molecule disorders disease in the EU by initiating and contributing to research and implementation of innovative therapies.

Organizational structure

The Neurotransmitter and small molecule disorders Core Network will consist of participating HCPs within the MetabERN with expertise in the field of neurotransmitter and small molecule disorders diseases and will build on or seek collaboration with existing international collaborations and networks of HCPs in the field of neurotransmitter and small molecule disorders diseases. Working groups will be formed to address different important topics within the field of neurotransmitter and small molecule disorders diseases.

These include:

  • Prevention & Screening for neurotransmitter and small molecule disorders diseases.
  • Diagnosis of (new) neurotransmitter and small molecule disorders diseases (including identification of biomarkers).
  • Management of neurotransmitter and small molecule disorders diseases (development of clinical guidelines & care paths).
  • Epidemiology & Outcome (participation in existing and development of new registries).
  • Education and Training (development of E-learning tools, work-shops and courses).
  • Virtual Counselling (for specific diseases at different HCPs with specific expertise).
  • Patient Empowerment (organization of patient meetings and interaction with patient organizations).
  • Research (fundamental, translational, clinical).

The executive board of the Neurotransmitter and small molecule disorders Core Network will formed by the chairpersons of the working groups. An advisory board (with members of patients organizations, policy makers, etc) will be appointed to monitor the different activities of the Neurotransmitter and small molecule disorders Core Network.

Disorders of neuromodulators and other small molecules

Coordinators

Angela Garcia Cazorla

Hospital Sant Joan de Déu, Esplugues. Barcelona, Spain.

Thomas Opladen

University Children’s Hospital in Heidelberg, Germany

Eliane Sardh

Karolinska University Hospital, Stockholm, Sweden