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

Common genetic disorders in KSA

• Haemoglobinopathies• Neuro-genetic diorders• Metabolic disorders• Inborn error of metabolism• Birth defects

Common genetic disorders in KSA

1-Chromosomal disorders e.g. Down syndrome, Turner syndrome2- Single gene defects (mendelian inheritance) -AR -AD -X-linked recessive -Multifactorial

Common genetic disorders in KSA

• Autosomal recessive disorders; SCD , thalasseia, CAH, GSD, CF, PKU, propionic acidemia, galactosemia.• Autosomal dominant disorders; Achondroplasia, c. spherocytosis, osteogenesis imperfecta, polycystic kidney disease, von-Willebrand disease.

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,club foot, ideopathic mental retardation Idiopathic epilepsy , neural tube defects, hirschsprung’s disease.

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,odd chain 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.

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.

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.

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.

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.

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.

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%

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.

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.

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.

Down syndrome

• Most common autosomal trisomy (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)

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.

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

Clinical features

• CHD 40 – 60 %,commonest , AVSD.• TEF. deudenal atresia , hirschsprung’s disease.• Male infertile, female can reproduce.• Prolonged neonatal jaundice , polycythemia,.• 20times high risk for leukemia.• Hypothyroidism .D. Mllitus.,gall stones

autosomal diseasea,repeated chest infections.

Diagnosis

• Karyotyping.• During pregnancy increase alpha feto proteins• Confirmation by chr. Study by villus biopsy &

amniocentesis.• USG of fetus,increase nuchal translucency.

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