Paediatrics College of Medicine K K U Abha K S A Common genetic disorders in KSA Haemoglobinopathies Neuro genetic diorders Metabolic disorders Inborn error of metabolism Birth defects ID: 911787
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Slide1
Dr . Muhammad
Rafique
Assist. Prof.
Paediatrics
College of Medicine
K
K
U
Abha
K S A
Slide2Common genetic disorders in KSA
Haemoglobinopathies
Neuro
-genetic
diorders
Metabolic disorders
Inborn error of metabolism
Birth defects
Slide3Common 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
Slide4Common 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.
Slide5Common 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.
Slide6Slide7Slide8Slide9Slide10Slide11Slide12Slide13Slide14Propionic acidemia
IEM,AR disorder, in KSA-incidence 1:2000-5000
Deficiency of enzyme Propionyl CoA
C
orboxylase.
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.
Slide15Clinical 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.
Slide16Laboratory 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.
Slide17diagnosis
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.
Slide18Long 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.
Slide19Treatment
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.
Slide20Sickle 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%
Slide21Clinical 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.
Slide22Diagnosis
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.
Slide23Treatment
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.
Slide24Slide25Slide26Slide27Slide28Slide29Down 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)
Slide30Slide31Slide32Clinical 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.
Slide33Risk 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
Slide34Slide35Slide36Clinical 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.
Slide37Diagnosis
Karyotyping
.
During pregnancy increase alpha
feto
proteins
Confirmation by
chr
. Study by
villus
biopsy & amniocentesis.
USG of
fetus,increase
nuchal
translucency.
Slide38Prevention & 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,
A
nti CCF
Tx
. And cardiac surgery for CHD.
Support for parents