1. Bruno Sopko

2. Genetics Biochemistry Clinical medicine

3.  GDM=cca 1/10 of rare diseases  Cca 700-800 nosologic units (>1000 genes)  Total incidence 1:500  Each GP has, at least, 1-2 patients with GDM  Cca 30% of these diseases are curable (100 diseases well) Rare diseases Prevalence < 1:2000 Rare diseases GDM

5. < 1500 Da> 1500 Da Acute toxicityyesno Chronic progression±yes Localizationcytosol, ECTmembranes Structural changesnoyes Diagnosisblood, urinetissue (urine) Originexogenousendogenous Dietary treatment, vitaminssuccessfulunsuccessful

6. < 1500 Da ◦ gases, inorganic ions ◦ Aminoacids ◦ organic acids ◦ Saccharides ◦ Polyols ◦ simple lipids ◦ purins, pyrimidins ◦ Vitamins ◦ oligomers: peptids up to cca 5- 10 AA, oligosaccharides  cytosol, mitochondrial stroma, blood, urine > 1500 Da ◦ Glycolipids ◦ Sphingolipids ◦ Plasmalogenes ◦ neutral polysaccharides (glycogen) ◦ Mucopolysaccharides (other oligomers: proteins, nucleic acids...)  Usually associated with membranes  Usually not observed in larger amounts in body fluids ( x MS/MS technology)

7. < 1500 Da  Dependent of exogenous intake  manifested (repeated) by acute toxicity, frequently accompanied by encephalopathy/coma  common hepatopathy  Frequent deviations in common biochemical tests-ammonia, ABB, ketone bodies, glycemia, uric acid...  Symptom occurence dependent on specific nutrition part, fasting catabolism  Possibly chronic (low toxicity)  Usually well cured by diet and vitamin supply > 1500 Da  Usually independent on exogenous nutrition supply  Frequently progressive  Possible fetal dysmorphia  Commonly impairment of nervous system and muscles  Organomegalia as theresulting from lysosomal storage diseases  Diet and vitamins do not have any long term effect

8.  Newborn (or neonatal) screening is a process of testing newborn babies for increased risk of certain rare diseases, which in case of early detection and early treatment can prevent serious injury to a child.  At the age of 48-72 hours after birth several drops of blood from the heel of the child are sampled on a special paper and sent for analysis to the screening laboratory. In the event that there was no suspicion of the screened disease (negative result), the respective laboratory does not issue a formal statement on normal findings.

9. Lysosmal storage disorders Aminoacidopathy, organic acidurias Fatty acid  -oxidation disorders Peroxisomal disorders Mitochondrial diseases Glycosylation disorders Others

10. 1. Endocrine Disorders ◦ Congenital hypothyroidism ◦ Congenital adrenal hyperplasia 2. Disturbances of amino acid metabolism ◦ Phenylketonuria ◦ Glutaric aciduria, Type I (glutaryl-CoA dehydrogenase deficiency) ◦ Isovaleryl-CoA dehydrogenase deficiency (Isovaleric acidemia) ◦ Maple syrup urine disease 3. Disorders of fatty acid oxidation ◦ Carnitine uptake/transporter defects ◦ Carnitine-acylcarnitine translocase deficiency ◦ Carnitine palmitoyl transferase I deficiency (CPT I) ◦ Carnitine palmitoyl transferase II deficiency (CPT II) ◦ Very long chain acyl-CoA dehydrogenase deficiency (VLCADD) ◦ Long chain L-3 hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) ◦ Medium chain acyl-CoA dehydrogenase deficiency (MCADD) 4. Cystic fibrosis ◦ Cystic fibrosis

12.  Autosomal recessive  Laboratory diagnosis: 17-hydroxyprogesterone - increased  Treatment – supplementing steroids  Girls – surgical correction

14. PKU HPA

15.  Autosomal recessive  Laboratory diagnosis: increased phenylalanine, and ratio Phe/Tyr  Treatment – alimentary – decreased intake Phe and supplemented Tyr

16.  Autosomal recessive  Laboratory diagnosis: Three level model IRT/DNA/IRT:  immunoreactive trypsinogen (IRT)  following DNA analysis  sweat test  Treatment:  Lungs: inhalation mucolytics + breathing physiotherapy in several (idealy 3) short blocks daily.  Well balanced nutrition, high caloric : 130 -150 % RDA, supplementing vitamins soluble in fats, supplementation of NaCl.  Infection control: antibiotics at all acute exacerbation respiratory infection, broad-spectrum antibiotics, with antistaphylococcus effect; when deteced Pseudomonas aeruginosa specific ATB therapy, even withou clinical manifestation. High limit dosages, at least 14 days.

17.  http://www.novorozeneckyscreening.cz http://www.novorozeneckyscreening.cz  Kožich, V. : Úvod do biochemické Genetiky  Jean-Marie Saudubray, Georges van den Berghe, John H. Walter:Inborn Metabolic  Diseases; Diagnosis and Treatment;Fifth Edition, Springer, 2012  William L. Nyhan, Bruce A. Barshop, Pinar T. Ozand, MD: Atlas of Metabolic Diseases; Second edition, Hodder Education,2005  Joe T. R. Clarke: A Clinical Guide to Inherited Metabolic Diseases;Second Edition, Cambridge University Press, 2004