Baby Detect : Genomic Newborn Screening

Study Overview
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Brief Summary
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Newborn screening (NBS) is a global initiative of systematic testing at birth to identify babies with pre-defined severe but treatable conditions. With a simple blood test, rare genetic conditions can be easily detected, and the early start of transformative treatment will help avoid severe disabilities and increase the quality of life. Baby Detect Project is an innovative NBS program using a panel of target sequencing that aims to identify 126 treatable severe early onset genetic diseases at birth caused by 361 genes. The list of diseases has been established in close collaboration with the Paediatricians of the University Hospital in Liege. The investigators use dedicated dried blood spots collected between the first day and 28 days of life of babies, after a consent sign by parents.

Detailed Description
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Every year, thousands of children around the world are born with rare genetic diseases leading to death or lifelong disability. With technological advancements in the field of genetics and medicine, the rate of introduction of treatments for these rare conditions has grown remarkably. However, timing is of great importance for medication administration. The benefit that can be measured in a patient who has already suffered from a long irreversible degenerative disorder is small and, sometimes, it hardly justifies the cost and the burden of the treatment. Early diagnosis is, thus, of primary importance both to obtain the best effect of the innovative medications and to accelerate their development. The investigators are pioneered in the field of genetic newborn screening (NBS) in rare diseases by funding, designing, and leading an innovative genetic NBS program initiated in March 2018 in Southern Belgium for Spinal Muscular Atrophy (SMA) that allowed, so far, for 11 children to be detected and treated early and avoid the terrible fate of the disease. The program was disseminated in 17 countries and included public dissemination and health-economic analysis since the very beginning [1]. (www.facebook.com/sunmayariseonsma). Drawing upon our experience with SMA screening, the investigators have designed a project to screen up to 40,000 newborns/year progressively in 3 years for virtually all the rare diseases that can benefit from treatment or a pre-symptomatic clinical trial. The methodology of Baby Detect includes sequencing of target genes on dried blood spots collected from the NBS cards in a timely and cost-efficient manner, and its high dynamicity allows for any newly treatable rare disease to be included in its scheme in no longer than 6 months. Baby Detect, as a multidisciplinary newborn screening program, involves expertise in areas from genetics and medicine to laboratory studies, computer science, Data Protection, Ethics, and health economy. It will constitute the proof of concept that is needed before moving to a whole region-scale population.

Official Title
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Universal Genomic Newborn Screening in the Wallonia-Brussels Federation: Baby Detect

Conditions
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Fructosemia, Fructose-1,6-Diphosphatase Deficiency, Citrullinemia 1, Adrenoleukodystrophy, Shwachman-Diamond Syndrome, Crigler-Najjar Syndrome, Charcot-Marie-Tooth Disease, Type 6C, Mucopolysaccharidosis I, Creatine Deficiency Syndrome, Jervell-Lange Nielsen Syndrome, Systemic Primary Carnitine Deficiency, Congenital Adrenal Hyperplasia, Familial Hyperinsulinemic Hypoglycemia 1, Phosphoglucomutase 1 Deficiency, Maturity Onset Diabetes of the Young, Cystic Fibrosis, Hypophosphatasia, Infantile, Congenital Hypothyroidism, Deficit in Anterior Pituitary Function and Variable Immunodeficiency, Diamond Blackfan Anemia, Wiskott-Aldrich Syndrome, Fanconi Anemia, Hemophilia A, Hemophilia B, Glucose 6 Phosphate Dehydrogenase Deficiency, Alpha-Thalassemia, Alpha 1-Antitrypsin Deficiency, Inflammatory Bowel Disease 25, Autosomal Recessive, Wilson Disease, Progressive Familial Intrahepatic Cholestasis, Familial Chylomicronemia, Lysosomal Acid Lipase Deficiency, Familial Hemophagocytic Lymphocytosis, Griscelli Syndrome, Chediak-Higashi Syndrome, Chronic Granulomatous Disease, Menkes Disease, Smith-Lemli-Opitz Syndrome, Ataxia With Vitamin E Deficiency, Thiamine Metabolism Dysfunction Syndrome 5 (Episodic Encephalopathy Type), Thiamine Metabolism Dysfunction Syndrome 4 (Bilateral Striatal Degeneration and Progressive Polyneuropathy Type), Thiamine-Responsive Megaloblastic Anemia, Thiamine Metabolism Dysfunction Syndrome 2, Sepiapterin Reductase Deficiency, Dopamine Beta Hydroxylase Deficiency, Glut1 Deficiency Syndrome, Late-Infantile Neuronal Ceroid Lipofuscinosis, Aromatic L-amino Acid Decarboxylase Deficiency, Hereditary Hyperekplexia, Brain Dopamine-Serotonin Vesicular Transport Disease, Very Long Chain Hydroxy Acyl Dehydrogenase Deficiency, Tyrosinemia, Type I, Disaccharide Intolerance I, Beta Ketothiolase Deficiency, Phosphoglycerate Dehydrogenase Deficiency, Succinyl-Coa:3-Ketoacid Coa-Transferase Deficiency, Pyridoxine-5'-Phosphate Oxidase Deficiency, Pompe Disease, Phenylalanine Hydroxylase Deficiency, Ornithine Transcarbamylase Deficiency, N Acetyl Glutamate Synthetase Deficiency, Riboflavin Deficiency, Isovaleric Acidemia, Phosphoserine Aminotransferase Deficiency, Phosphoserine Phosphatase Deficiency, Hyperornithinemia-Hyperammonemia-Homocitrullinuria, S-Adenosylhomocysteine Hydrolase Deficiency, Mucopolysaccharidosis VI, Mucopolysaccharidosis IV A, Mucopolysaccharidosis II, Transcobalamin Deficiency, Isolated Methylmalonic Acidemia, Cobalamin Deficiency, Homocystinuria, Holocarboxylase Synthetase Deficiency, Fanconi Bickel Syndrome, Glycogen Storage Disease, Glycine Encephalopathy, Glutaric Acidemia I, Glucose Galactose Malabsorption, Gaucher Disease, Type 1, Carbamoyl Phosphate Synthase 1 Deficiency, Citrullinemia Type II, Carnitine Palmitoyltransferase Deficiency 2, Carnitine Palmitoyltransferase Deficiency 1, Carnitine Acylcarnitine Translocase Deficiency, Riboflavin Transporter Deficiency, Andersen Tawil Syndrome, Timothy Syndrome, Catecholaminergic Polymorphic Ventricular Tachycardia, Familial Hypertrophic Cardiomyopathy Type 4, Primary Hyperoxaluria, X Linked Hypophosphatemia, Hereditary Nephrogenic Diabetes Insipidus, Cystinosis, Congenital Nephrotic Syndrome, Finnish Type, Alport Syndrome, Hereditary Retinoblastoma, Biotinidase Deficiency, Aciduria, Argininosuccinic, Argininemia, Acyl-CoA Dehydrogenase Family, Member 9, Deficiency of, 3-Hydroxy 3-Methyl Glutaric Aciduria, 3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 Deficiency, Maple Syrup Urine Disease, Medium Chain Acyl CoA Dehydrogenase Deficiency, Long-chain 3-hydroxyacyl-CoA Dehydrogenase Deficiency, Malonic Acidemia, Sickle Cell Disease, Severe Congenital Neutropenia, Severe Combined Immune Deficiency, Deficiency of GOT2, Cerebral Folate Transport Deficiency, Segawa Syndrome, Autosomal Recessive, Congenital Myasthenic Syndrome, Metachromatic Leukodystrophy, Pyridoxine-Dependent Epilepsy, Propionic Acidemia, Mucopolysaccharidosis VII, Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency, Pseudohypoaldosteronism, Type II, Pseudohypoaldosteronism Type 1, Pituitary Hormone Deficiency, Combined, Galactosemias

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: newborn between birth and 28 days of life consent of parent Exclusion Criteria: + 28 days Non consent of parent

Ages Eligible for Study
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Maximum Age: 28 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Newborns with consent<br>Newborns with parent's consent | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acceptability | The percentage of parents accepting the proposed screening in comparison with the number of mothers approached for consent | through study completion, an average of 1 year | 
| Feasibility - timing | The Turn-around time for the different mutations that are screened | through study completion, an average of 1 year | 
| Feasibility - reliability | The percentage of false positives and the predicted value for each test The estimation of the false negatives through collaboration with physicians treating the different diseases. | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Consequence of NBS on early treatment access - timing | The time passed between the birth of diagnostic-positive newborns to the initiation of their treatment | through study completion, an average of 1 year | 
| Consequence of NBS on early treatment access - frequency | The number of patients offered early treatment | through study completion, an average of 1 year | 
| To improve the detection technique for disease related mutations that are not detected in classical screening by improving the classification of unspecified variants. | The number of new mutations implemented yearly in the NBS. | through study completion, an average of 1 year |