Transcript Propionic acidemia

Dr . Muhammad Rafique
Assist. Prof. Paediatrics
College of Medicine
K K U Abha K S A
Common genetic disorders in KSA
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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 syndrome
2- 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- lethargydehydration-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
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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
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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
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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
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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
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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
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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
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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
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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