EU/MPRL/0169/Septiembre2019

SSIEMVI POST

AVALADO POR: AVALADO POR:

Apreciados amigos

Es un placer para mí, una vez más, poder coordinar la VI reunión

científica Post-SSIEM 2019, que se celebrará en Santander dentro

del marco del congreso de AECOM, el próximo día 16 de Octubre y

que nos ofrece la oportunidad de, como en años anteriores, poder

resumir el congreso SSIEM que tuvo lugar en Rotterdam, a todos

aquellos profesionales interesados o que no pudieron asistir.

Los resúmenes que se os presentarán están divididos por los diversos

errores congénitos del Metabolismo, dando a cada profesional una o

varias vías metabólicas de las cuales considero que son expertos.

Cada uno de los ponentes va a exponer lo que ha considerado más

novedoso y significativo de las diferentes charlas que tuvieron lugar

durante el congreso, tanto Sesiones Plenarias, como Paralelas o

Simposios.

Estoy segura de que también este año será todo un éxito y de gran

interés y provecho para cada uno de nosotros.

Nos vemos en Santander!!

Un saludo,

M. Pineda

SSIEMVI POST

Dra. Mercedes Pineda Marfa

Patrocinado por:

Patrocinado por:

1 4 : 3 0 - 1 6 : 0 0 H . RECOGIDA DE DOCUMENTACIÓN

16:10H. PRESENTACIÓN Dr. Domingo Gonzalez Lamuño Presidente Comité Organizador AECOMDra. Mercé Pineda Coordinadora Post-SSIEM

16:10 - 16:25 H. SESIÓN I Dr. C. Colón Hospital Clinico Universitario de Santiago de Compostela

ERNDIM MeetingERNDIM Workshop

› ETAC Meeting.NBS MeetingSimposio APR: Physiological absorption of Amino Acids: Nitrogen Balance and Patient Outcomes

› Prolonged release of amino acids: what is it and why is it important.› Physiological absorption of amino acids: Preclinical evidences of a different outcome.› Patient reciving prolonged-release amino acids for PKU management: initial evidences.› Panel discussion.

Simposio TAKEDA: Re-evaluating short- and long-term management goals for lysosomal diseases› Lyso-Gb1 as an established biomarker for Gaucher disease clinical outcomes.› The search for biomarkers and treatment goals in Fabry disease.› Impact of long-term treatment on the somatic and neurological manifestations of MPS II.› Panel discussion and Conclusions.

Plenary Session 5: Metabolomics / System biology› Modeling human metabolism in health and disease.› Innovative analytical tools for metabolomics-driven systems biology in personalized health strategies. Metabolomics & high throughput analysis to investigate monogenetic and complex disorders.› Integrative network biology approaches to understand rare inborn error of metabolism.

Simposio AMICUS: Fabry Disease: The Pharmacogenomic Approach› Alpha Galacosidase A - Our Therapeutic Approach.› Application of the GLP HEK Assay in Determining Amenability.› Pharmacogenomics - Translatin Evidence into Practice.› Q&A.

16:25 - 16:40 H. SESIÓN II Dr. M. Bueno Hospital Virgen del Rocio (Sevilla)

Dietician group / Nutrition & Dietetic Session› The use of body composition as a clinical tool in IEM.› GSD - New treatments; KD/High protein v traditional treatment.› Ketogenic diet in Inborn Errors of Metabolism: experience from one center and introduction of Ketogenic PN guideline.

Dietician group / Nutrition & Dietetic Session› Citrin Deficiency; recent developments.› 10 year follow up of PKU: implications of dietary therapy on weight management/ metabolic syndrome.› Evaluation of UX007 in patients with severe LC-FAOD.

Simposio VITAFLO: Preliminary results from the Glyde Trail. The first randomised double blind crossover trial on the dietary management of Glycongen Store Parallel Session 2C: Nutricion and Dietetics

› Update Lecture: Working mechanism of ketogenic diet.› Outcome after liver transplantation in paediatric IMD- survival, growth and hospital admissions experience from one centre.› The dietetic and biochemical basis of trimethylaminuria in one Adult Metabolic Centre.› Arginine supplementation’s impact on lysine metabolism in humans: A proof-of-concept for lysine-related inborn errors of metabolism.› MyRareDiet®: A diet tracking and monitoring mHEALTH tool for research and clinical care for patients with inborn errors of metabolism.

16:40 - 16:55 H. SESIÓN III Dra. A. Belanger Hospital Ramón y Cajal (MAD)

Parallel Session 1B: Amino acid disorders (including PKU) and urea cycle disorders› Targeting CPS1: From CPS1 deficiency to lung tumor regression.› Enhancement of hepatic autophagy for therapy of argininosuccinic aciduria.› First crystal structure of DHTKD1 provides insight into catalysis and disorders of lysine metabolism.› A Phase 1/2a Oral Placebo-controlled Study of SYNB1618 in Healthy Adult Volunteers and Subjects with Phenylketonuria.› Pharmacologic rescue of hyperammonemia-induced neurotixicity by OAT-inhibitiion in a zebrafish model of acute hyperammonemic encephalopathy.› Manipulating folate metabolism achieves near-normal homocysteine without methionine restriction in homocystinuric mice.

Parallel Session 2B: Advances in diagnostics (including omics)› The ‘Cryo-Electron Microscopy Revolution’ for structure determination of metabolic enzyme complexes.› Discovery of novel antiquitin deficiency biomarkers through the combination of untargeted metabolomics and infrared ion spectroscopy.› The Impact of Mitochondrial Bioenergetics on Metabolic Pathways by Real-time NMR of 3D Cell Cultures.› Multiplex testing for the diagnosis of disorders involving sulfatide degradation.› Algorithms for interpretation of (multi)-omics in metabolic diagnostics.› Mitochondrial DNA mutation analysis from exome sequencing – a holistic approach in diagnostics of mitochondrial disease.

Parallel Session 3C: Disease modeling› Zebrafish as a model to study cystinosis: from pathophysiology to drug screening.› Increased ammonium production and reduced appetite in a knock-in rat model for glutaric aciduria type I challenged with high lysine diet.› CRISPR/Cas9-mediated editing of hepatic G6pc in mice allows to investigate the clinical spectrum of glycogen storage disease type Ia.› Molecular and metabolic consequences of renal carnosinase deficiency.› Brain on a chip; disease modeling and drug screening in a neurophysiological model of MELAS disease› Engineered human iPSC-derived skeletal muscles to model Pompe disease

16:55 - 17:10 H. SESIÓN IV Dr. A. Hermida Hospital Clínico Universitario Santiago de Compostela

Adult Group Session: Lifestyle in adults with IMD› Exercise in adults with IMD.› Diet, overweight and obesity.› Independence, parenting, non-adherence and psychosocial issues.

Simposio BIOMARIN: Navigating and understanding consequences of high Phe in PKU› Consequences of lifelong high Phe.› Diving into the pathways of neurotransmitters in PKU.› Preventing Phe damage by lifelong follow-up.› Interactive discussion.

Simposio BIOMARIN: Turning the tide in PKU, the role of Palynziq› Changing the treatment landscape of PKU: Phase 3 study results.› Clinical considerations to achieve optimal Palynziq treatment.› The dietitian’s role: Before, during and after Palynziq treatment.› My personal journey with Palynziq – A patient’s perspective.› Q&A.

17:10 - 17:25 H. SESIÓN V Dra. M. Morales Hospital 12 de Ocubre (MAD)

Adult Group Session: Oral Presentations› Adherence to dietary treatment and psychological outcomes in adults with early-treated Phenylketonuria.› Diffusion Kurtosis Characterisation of White Matter Abnormalities in Phenylketonuria: A Study of Divergent Siblings, with a Subsequent Analysis in 22 Adults.› Coping, Health Perception And Pain Are Related To Depressive Symptoms In Fabry Disease.› Acute neurological decompensation in adults with Tyrosinemia type 1 – an emerging issue?.› Follow-up of five, non-MELAS phenotype, adult patients with m.3243A>G mutation after kidney transplantation and a review of the literature.

Simposio SOBI: The role of glycerol phenylbutyrate in the management of UCD: Bridging the gap between clinical data and real world experience

› Glycerol phenylbutyrate data and clinical experience.› Practical experience of glycerol phenylbutyrate as an alternative to sodium benzoate.

Parallel Session 4C: Metabolic disorders in adults› Eye movement disorders as an aid to early detection of late-onset inborn errors of metabolism.› Does nitisinone modify ochronosis in alkaptonuria - experience from the United Kingdom National Alkaptonuria Centre.› Atypical cerebral palsy: yield of genetic diagnostics in the adult metabolic disease clinic.› Longitudinal cohort study of cardiac complications in Fabry disease.› Metabolic control modulates neuropsychiatric involvement, brain damage and neurodegenerative markers in adult henylketonuria patients.› Are we failing to support the cognitive and mental health of adults with IMDs? Developing neuropsychology services in one Metabolic Centre.

17:25 - 17:40 H. SESIÓN VI Dra. M. L. Couce Hospital Clínico Universitario Santiago de Compostela

Garrod Award Lecture:Simposio NUTRICIA: Setting solid foundations in early life. The importance of nutrition for the fetus, infant and growing child with IEM

› Pre- and postnatal nutritional interaction between mother and child.› Relevance of precision nutrition in early life.› The impact of nutricion in the growing child.

Simposio SANOFI GENZYME: Drug-target and disease networks: rethinking the role of glucosylceramide synthase› Inborn errors of sphingolipid metabolism: Convergence of pathogenic mechanisms with those of common human diseases.› Targeting Glucosylceramide Synthesis: Fundamental studies in the treatment of rare and common diseases.› Q&A.

Simposio SANOFI GENZYME: When to treat late-onset Pompe disease? The latest view from pathology to clinical evidence and guidelines› Clues & Evidence from the Pathology Perspective.› A Closer Look at Clinical Evidence and Real World Data.› A Deep Dive into the latest EPOC Treatment Guidelines - when to start/maintain/stop?.› Q&A

P A U S A C F É

18:10 - 18:25 H. SESIÓN VII Dra. A. Garcia Cazorla Hospital Sant Joan de Deu (BCN)

Parallel Session 1D: Disorders of haem biosynthesis, vitamins, purines and pyrimidines› New insights in pysidoxamine 5’-phosphate oxidase (PNPO) deficiency from zebrafish and cell models.› Gamma aminobutyric acid and tricarboxylic acid pathways in knock-out aldh7a1 zebrafish for pyridoxine-dependent epilepsy.› PLPHP deficiency: Clinical, genetic, biochemical, and mechanistic insights.› Clinical effectiveness of afamelanotide in patients with erythropoietic protoporphyria: an observational study.› Induced pluripotent stem cells and iPSC-derived cerebral organoids as a model of Succinic Semialdehyde Dehydrogenase Deficiency.› Thymidylate kinase deficiency due to mutations in TYMK is the cause of a novel vanishing white matter disease.

Plenary Session 4: Mitochondrial› Moving towards clinical trials for mitochondrial disease.› The pursuit of precision mitochondrial medicine: Harnessing pre-clinical cellular and animal models of mitochondrial disease.› Mitochondrial in Alzheimer disease: It’s not what you think.

Simposio RECORDATI: Exploring long-term strategies for patients with propionic and methylmalonic aciduriasKomrower Lecture

› From fatty acid oxidation to riboflavin - Make metabolites great again!

18:25 - 18:40 H. SESIÓN VIII Dr. A. Gonzalez Meneses Hospital Virgen del Rocio (Sevilla)

Parallel Session 1C: Glycosylation and carbohydrate disorders › D-galactose supplementation in SLC35A2-CDG leads to clinical and biochemical improvement.› Crystal structure of human PMM2 enzyme as a model to evaulate missense variants amenable to be rescued using pharmacological chaperones.› Glycoproteomics for improved diagnosis of the Congenital Disorders of Glycosylation (CDG).› Using tracer metabolomics to investigate metabolic effects of galactose in different CDG.› Nucleotide sugar profile in the galactosemia zebrafish model reveals new pathogenic mechanisms and potencial readouts.› Biallelic GALM pathogenic variants cause type IV galactosemia.

Parallel Session 3A: Disorders of fatty acid oxidation and metabolic myopathies › Update Lecture: Latest insights into metabolic myopathies.› A mutation creating an upstream translation initiation codon in SLC22A5 5’UTR is a frequent cause of primary carnitine deficiency.› Implication of post-translational modifications on ETF, a Multiple Acyl-CoA Dehydrogenase Deficiency related enzyme.› Novel genetic discoveries in 14 patients with multiple acyl-CoA dehydrogenation deficiency using whole exome sequencing and RNA-seq.› Modified ketogenic diet in patients with Glycogen Storage Disease type V – a pilot study.

Parallel Session 4D: Novel disease genes › RINT1 biallelic variants cause a novel disorder of infantile onset recurrent acute liver failure and skeletal anomalies.› Mutations in PCYT2 disrupt etherlipid biosynthesis and cause a complex hereditary spastic paraplegia.› Possible new peroxisomal disorder associated with IDI1 mutation and identified on global metabolomics study.› MDH1 deficiency is a metabolic disorder of the malate-aspartate shuttle associated with early onset severe encephalopathy.› Identification of mutations in mitochondrial ribosomal protein PTCD3 as a novel cause of Leigh syndrome.› Identification of an autosomal dominant Zellweger Spectrum Disorder.

18:40 - 18:55H. SESIÓN IX Dr. D. Gonzalez-Lamuño Hospital Marqués de Valdecilla (Santander)

Simposio AEGLEA: The Story of Arginase 1 Deficiency: Time for a New Chapter› Arginase 1 deficiensy: From the beginning.› Understanding the cast of characters.› The plot thickens: A look ahead to a potential new treatment approach.› Can we change the ending?.

Parallel Session 4B: Educational Session: CRISPR/CAS› Basics and clinical applications of gene editing: hopes, hypes and hurdles.› Improving gene editing outcomes: separating the good from the bad and ugly.› A bright future for plant genome editing: implications for global food production and societies.

Parallel Session 3B: Organic Acidurias› Update Lecture: Organic acidurias – it’s about time to bridge the gaps.› Genetic, structural, and functional analysis of pathogenic variations causing methylmalonyl-CoA epimerase deficiency.› Long-term outcome of methylmalonic aciduria after kidney, liver or combined liver-kidney transplantation: the French experience.› DHTKD1 and OGDH form a hybrid ketoacid dehydrogenase complex with functional redundancy toward a-ketoadipic acid?.› Metabolic liver disease in a tailored mouse model of mut-type methylmalonic aciduria.

18:55 - 19:10 H. SESIÓN X Dr. G. Pintos Hospital Vall d’Hebron (BCN)

Plenary Session 1: Building Bridges› Organoids as models of human disease.› The role of DNA damage repair and transcription stress in aging and the impact of nutricion.› The Lysosome as a control center of cell metabolism.

Plenary Session 3: Regenerative medicine› Hurdles in successful examples of stem cell-based regenerative medicine.› Ex vivo gene editing studies with human hepatocytes from patients with urea cycle defects.› Human induced pluripotent stem cells come of age in modeling cardiovascular disease.

Parallel Session 3D: Patient cohorts and follow-up› Patterns of abnormal movements in neonatal inborn errors of metabolism: study following videofilmation analysis and volumetric brain MRI.› Genotype-phenotype correlation and natural history in NBAS deficiency.› Follow-up of patients identified by MPS I newborn screening.› Very long-term follow-up of a series of patients with CblA deficiency.› PEX12 gene mutation causing a peroxisomal biogenesis disorder among Egyptian patients with founder mutations. › Clinical, biochemical and genetic characteristics of a cohort of 101 French and Italian patients with HPRT deficiency.

Plenary Session 6: Lysosomes-Innovative insights› Disorders of lysosome-related organelle biogenesis.› Challenges and concepts to combat diseases caused by dificiencies of lysosomal hydrolases and membrane proteins.› The future of therapies for Lysosomal disorders, lessons from the past.

19:10 - 19:25 H. SESIÓN XI Dra. M. O’Callaghan Hospital Sant Joan de Deu (BCN)

Plenary Session 2: RNA based therapy and Gene therapy› AAV gene therapy for inherited diseases.› HSC gene therapy for neurometabolic and neurogenerative disorders.› Opportunities and challenges for RNA therapy development.

Parallel Session 1A: Gene Therapy› A phase 1/2 clinical trial of AAV8 gene therapy in adults with late-onset OTC deficiency: CAPtivate cohort 1+2 results.› Hematopoietic stem cell gene therapy for Mucopolysaccharidosis tipe I, Hurler variant (MPS-IH).› Lentiviral hematopoiteic stem cell gene therapy for metachromatic leukodystrophy (MLD) provides sustained clinical benefit.› Three year open label phase 2a investigation of venglustat safety and exploratory efficacy in classic Fabry patients.› Positive cohort 1 results from the phase 1/2, AAV8-mediated liver-directed gene therapy trial in glycogen store disease type Ia.› AAV Gene Therapy For Glycogen Store Disease Type 3.

Simposio LYSOGENE SAREPTA: The Advancing Science of Brain Directed Gene Therapy› Evolving gene therapy landscape targeting the CNS.› The rationale for direct to CNS gene therapy.› Novel outcomes in neurodegenerative gene therapy trials.

19:25 - 19:40 H. SESIÓN XII Dra. M. del Toro Hospital Vall d’Hebron (BCN)

Parallel Session 2A: Lysosomal storage disorders › Benefits of higher and more frequent dosing and immunomodulation on long-term outcome in classic infantile Pompe disease.› A natural disease history study and a meta-analysis of published cases improve clinical knowledge on Multiple Sulfatase Deficiency.› Acid ceramidase deficiency presenting as Farber disease: prospective and retrospective clinical data from an ongoing natural history study.› Persistent treatment effect of cerliponase alfa in children with CLN2 disease: A 3 year update from an ongoing multicenter extension study.› Losartan or Propanolol treatment restores Erk1/2 activity during the cardiac remodelling of mucopolysaccharidosis type-I mice.› Intrathecal VTS-270 For The Treatment Of Niemann-Pick Disease, Type C1.

Simposio BIOMARIN: Improving patient care in MPS VI and MPS IVA: From Evidence to Consensus› Challenges of rare diseases.› Reducing the dianotistc delay in MPS - How?.› Keeping MPS patients on treatment - Why?.› My Journey with MPS - a patient perspective.› Q&A.

Parallel Session 4A: Mitochondrial disorders› KGD4 biallelic variants in two siblings with bilateral striatal necrosis: a new gene of Krebs cycle associated with Leigh syndrome.› Interferon signature: a new biomarker to follow disease progression in Pearson and Kearns-Sayre syndrome.› Assay for simultaneous evaluation of aminoacyl-tRNA synthetase activities: application to mitochondrial aspartyl tRNA synthetase.› No effect of Resveratrol supplementation in patients with mitochondrial myopathy – a randomized, double-blind, cross-over study.› A six year prospective follow-up study in 151 carriers of the m.3243A>G mutation.› Mutations in SQOR encoding sulfide:quinone oxidoreductase are a potentially treatable cause of Leigh disease.

Late Breaking News› Mutations in PDXK cause a polyneuropathy that responds to treatment with vitamin B6.› Biallelic truncating SOD1 variants with loss of enzymatic activity: a novel neurometabolic disorder.› Treatment with an SGLT2 inhibitor improves neutropenia-related signs and symptoms in four GSD1b patients.› DEGS1-Leukodystrophy, a novel disorder of sphingolipid metabolism impacts mitochondria dynamics.

C I E R R E D E J O R N A D A