Assistance Publique-Hôpitaux de Paris-University Hospital Necker-Enfants Malades

Paris, FRANCE

Area of expertise and the Healthcare Provider’s contribution to care for patients within the MetabERN Network

APHP-Necker is a paediatric and adult university hospital (70% activity for child health), with 600 beds, 700 medical staff, 3 200 paramedical staff, 62000 hospitalisations per year, 74000 emergency consultations, 2400 births. 250 paediatric and adult organ transplants are performed, 100 000 imaging analysis and 140 million laboratory analysis. Specialised medical activities are closely linked with 32 centres for rare diseases and 22 research units staffed by 600 scientists. IMAGINE and INEM provide the infrastructures to integrate research with clinical care. APHP-Necker is involved in one thousand peer reviewed publications per year. The Laennec project launched in 2012. The IMD centre sees over 1300 patients with just under 300 new diagnosis per year (children and adults). 5% of consultations are from abroad. APHP-Necker collaborates with other national centres and has been central in the establishment of the IMD national network “filiere de santé maladies rares”. APHP-Necker will make important contributions to the IMD ERN (MetabERN) in the following areas: Expertise in multidisciplinary care with specialised paediatric services. Since IMD involve multi-organs, coordination is required between specialities. This multidisciplinary approach also includes dieticians, social services, rehabilitation and palliative needs (staffs, multidisciplinary consultations). It provides a high quality planned transition care and support programme from the paediatric unit to adult services, and a patient educational programme (“Education thérapeutique”). Also, SAMU, cultural mediation, ethical staffs. The aim is to help patients and families take control of their disease, with the development of accessible information adapted to the specific needs of patients and their family, with IMD patient groups through meetings, presentations, training and distributing information at the centre. Specialised laboratories testing facilities, especially biochemists and geneticists ensures an early diagnosis. Good practice guidelines: contribution to the elaboration of national and international good practice guidelines in several disease areas: phenylketonuria, mucopolysaccharidosis, urea cycle diseases, Gaucher, and soon hyperinsulinism. Education and training: activities include training for pre-graduate, graduate and fellows, Foreign medical doctors. P de Lonlay is coordinator of the metabolic DU (Paris Descartes University). APHP-Necker is part of national and international IMD professional societies, lectures at the SSIEM Academy educational courses. Articles are regularly published in GP journals. APHP-Necker is involved in research and development for ERT, small molecules and gene therapy, natural history studies, feasibility studies, long-term effects of new treatments. Registries and data collection: APHP-Necker contributes to the national registry of rare diseases (BAMARA) and is involved in a national cohort study on MPS (RADICO).

SPECIFIC TREATMENTS AND INTERVENTIONS PROVIDED BY THE HCPs

The progress in understanding the pathophysiology of the majority of IEM has led to the discovery of several new therapies that have made it possible to attenuate the severity of the clinical manifestations associated with many of these diseases. APHP-Necker provides the following specific treatments and interventions:
– Inborn errors of metabolism that respond to dietary therapy (therapeutical education)
– Cookery classes; Examples of IEM that respond to treatment with cofactors or vitamins
– Hemodialysis, -filtration (intoxication diseases: urea cycle disease, organic acidurias, Maple syrup urine disease (MSUD); rhabdomyolysis; children and adults.
– Corticoids in acute episodes of inherited metabolic diseases (Lipin-1 deficiency): unpublished yet.
– Surgery of focal hyperinsulinism and anti-mTOR in hyperinsulinism.
– Small molecules : mannose in CDG Ib (Necker: expert); serine, creatine, …
– Enzyme replacement therapy for the treatment of several LSDs. APHP-Necker provides the structure for i.v. administration of Aldurazyme® for the treatment of MPS I, Elaprase® for MPS II, Naglazyme® for MPS VI, Vimizim® for MPS IVA, Replagal® and Fabrazyme® for Fabry disease and Myozyme® for Pompe disease. Clinical trials are ongoing in lipase acid deficiency with intraveinous ERT with Sebelipase acid (Kanuma®) which has been recently approved by FDA and EMEA (our center was a major center of clinical trial for this disease). Studies for ERT delivered into the cerebrospinal fluid via surgically implanted drug delivery devices are ongoing to prevent the progression of the neurological symptoms in LSDs with CNS involvement.
– Organ transplantation for children : kidney to treat chronic renal failure (Organic acidurias, Fabry disease, cystinosis); liver (urea cycle diseases, organic acidurias, energetic diseases, …; cornea (MPS, cystinosis); heart (cardiomyopathy); Hematopoietic cell transplantation. Adults: renal and hematopoietic cell. transplantations.
– Inhibition of substrate synthesis.
– Depletion of accumulated substrate.
– Gene therapy: APHP-Necker is involved in several gene therapy clinical trials and has been the European leader in gene therapy trials delivered to the CNS.
– “Hospitalisation A Domicile” (HAD, at home hospitalization service)
– Expertise in multiple reeducations, palliative care, ethical and cultural difficult situations: ethical questions due to the “multidisciplinary patients”, complex cases (Dr Canoui, Dr Viallard, Pr Mamzer, intensive unit care), and cultural mediation due to the collaboration with Dr Serge Bouznah (maison de Solenn, maison des ados). This expertise has been accumulated over the years for the care of IMD (medical and dietary care) and other rare diseases.

For an overview of the enzyme and genetic testing that is being offered, click here.

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    Pascal De Lonlay

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