Dr . Muhammad Rafique Assist. Prof. Paediatrics College of Medicine K K U Abha K S A

1. Dr . Muhammad RafiqueAssist. Prof. PaediatricsCollege of MedicineK K U Abha K S A

2. Common genetic disorders in KSA • Haemoglobinopathies • Neuro-genetic diorders • Metabolic disorders • Inborn error of metabolism • Birth defects

3. Common genetic disorders in KSA 1-Chromosomal disorders e.g. Down syndrome, Turner syndrome 2- Single gene defects (mendelian inheritance) -AR -AD -X-linked recessive -Multifactorial

4. Common genetic disorders in KSA • Autosomalrecessive disorders; SCD , thalasseia, CAH, GSD, CF, PKU, propionicacidemia, galactosemia. • Autosomal dominant disorders; Achondroplasia, c. spherocytosis, osteogenesisimperfecta, polycystic kidney disease, von-Willebrand disease.

5. Common genetic disorders in KSA • X-linked recessive disorders; Haemophilia A & B , G-6PD deficiency. • Multifactorial disorders; cleft lip & palat, D. mellitus , asthma , CHD, childhood obesity, pyloric stenosis , CD of hip,clubfoot, ideopathicmental retardation Idiopathic epilepsy , neural tube defects, hirschsprung’s disease.

14. Propionic acidemia • IEM,AR disorder, in KSA-incidence 1:2000-5000 • Deficiency of enzyme Propionyl CoA Corboxylase. • It is intermediate metabolite of isoleucine, valine threonine, methionine,oddchain fatty acids and cholesterol catabolism. • Mutant gene found for alpha subunit on 3q21-22 and for beta subunit on 13q32 . • Episode triggered- infection,constipation,high PD.

15. Clinical findings • Sever form present in neonatal period with –poor feeding- vomiting- hypotonia- lethargy-dehydration-ketoacidosis-coma & death. • Milder form ,infant may have MR , episodes of unexplained sever ketoacidosis. • Variable severity even in same family member • Older survivors have MR , dystonia, chorioethetosis , tremors and pyramidal signs.

16. Laboratory findings • In episode sever metabolic acidosis neutropenia , thrombocytopenia hypoglycemia& high ammonia • High propionic acid in plasma and urine. • MRI and CT Scan brain show cerebral atrophy, demyelination due to past inforction as a result of metabolic stroke, cause of neurological sequelae.

17. diagnosis • Metabolic & MRI&CT brain findings , suggests. • Definitive Dx. By low enzyme activity in leukocytes and cultured fibroblasts. • Prenatal diagnosis possible by enzyme activity in amniocytes.

18. Long term treatment • Low protein diet, synthetic proteins. • Chronic alkaline therapy to correct ch. acidosis • Monitor growth parameters. • Long term prognosis is guarded. • Normal psychomotor development possible in milder forms. • Neurodevelopment deficit is dystonia, pyramidal signs and choreoethetosis.

19. Treatment • Correct dehydration with normal saline. • Correct acidosis with NaHCo3 . • Correct hypoglycemia with I/V dextrose water. • Minimal amount of proteins 0.25 g/kg/day. • Antibiotics, oral neomycin and also systemic. • L-cornitine 50-100 mg/kg/day. • Lower plasma ammonia, by sodium benzoate and if necessary by dialysis. • Biotin 10 mg/day orally.

20. Sickle cell anaemia/SCD • Hb. Molecule is tetramer(4 globin chains= 2 alpha & 2 beta chains) ,controlled by 2 genes. • AR disorder , common in KSA, gene at chr. 6. • SCA both genes have SC mutation. Hb-F=90%. • SCD, one gene has SC mutation one an other, like beta thalassemia, Hb.O Arab.Hb.F=50%

21. Clinical manifestations • Painful crises, abdomen, chest,bones, back etc. • Haemolytic crises, pallor, jaundace,fatigue.etc. • Aplastic crises,depressed 3 series of cells. • Vaso-occlusive crises, pain, stroke. • Infection-functional asplenia,poor opsonization • Splenic sequestration, Size increase. • Precipitating factors- acidosis,exposure to cold. ,physical stress, dehydration,hypoxia,infection.

22. Diagnosis • Hb., cell count, peripheral blood picture. • Hb. electrophoresis. Hb-S 50-90%. • X-ray chest& hands , pulse oximetry, ABG’s. • MRI,CT-Scan brain to Dx. Inforction. • Trans-cranial MRA scan to predict stroke. • S.Bilirbin, urine c/e, blood c/s, CSF exam. • Pre-natal Dx. Possible by gene study. • Pre marital and newborn screening –must.

23. Treatment • Admit. Hydrate, O2 therapy. • blood exchange/ transfusion. • Pain relief- paracetamol/ morphine. • Antibiotics. • Long term treatment; -Avoid hypoxic condition. -Prophylactic vaccination& penicillin. -Folic acid, hydroxy urea, parent counseling.

29. Down syndrome • Most common autosomaltrisomy (chr. 21) comatible with life. • 95 % due to non disjunction. • 4% translocation b/w d & g group chr. • If father carrier ,recurrence 2-10 %. • If mother carrier ,recurrence 5-15% • 1% mosaic (normal & abnormal cells mixture)

32. Clinical features • Gross generalized hypotonia. • Mental retadation. • Short stature. • Brachycephally (flat occiput) • Upward eye slant, medial epicanthic fold. • Tongue appears large and protruded. • Short and broad hand , single simian crease in 50%,Clinodactly , sandle sign in foot.

33. Risk incidence • Risk in non disjunction cases increases with increasing maternal age. • General population risk in females 1:700 • Maternal age < 25years Risk—1:2000 • Maternal age 35-39 years Risk—1:50 • Maternal age >40 years Risk—1:20

36. Clinical features • CHD 40 – 60 %,commonest , AVSD. • TEF. deudenalatresia , hirschsprung’s disease. • Male infertile, female can reproduce. • Prolonged neonatal jaundice , polycythemia,. • 20times high risk for leukemia. • Hypothyroidism .D. Mllitus.,gall stones autosomaldiseasea,repeated chest infections.

37. Diagnosis • Karyotyping. • During pregnancy increase alpha feto proteins • Confirmation by chr. Study by villus biopsy & amniocentesis. • USG of fetus,increasenuchal translucency.

38. Prevention & treatment • Avoid late child bearing (after 35 years) • Family planning,Pre natal Dx.&proper decision • No treatment for disorders. • Therapy is directed to specific problem,e.g. antibiotic for infections, • Anti CCF Tx. And cardiac surgery for CHD. • Support for parents