Dr.Ghualam Murtaza chemical pathology pgy2 (esp. thanks to my supervisor Dr.Sahar Iqbal fcps Consultant chemical Pathology )

1. New born screening
&
inborn error of
metabolism
DR.GHULAM MURTAZA
CHEMICAL PATHOLOGY PGY2

2. Definition :
o Metabolic disorders Result from the absence or abnormality of an enzyme or its
cofactor leading to either accumulation or deficiency! of a specific metabolite .
o Individual IMD is not very common (1:5,000 to 1:10,000) ,However collectively as a
group the incidence is around1:800.
o Management! of certain symptoms! like hypoglycemia, hyperammonemia, and
seizures must be initiated promptly before exact diagnosis to prevent long term
sequelae

3. Initial Evaluation : Hx
o family history of metabolic disease or members with similar presentations
o Antenatal or Birth history should be obtained in all cases
o Recurrent vomiting and or diarrhea
o Intolerance to feeds
o Episodic abdominal pain ,Lethargy ,Failure to thrive/developmental delay ,Fits
o Recurrent hypoglycemia

4. Age at presentation
I. Diseases like urea cycle disorders,
non ketotic hyperglycinemia, & branched chain organic acidemias often present during the first
few hours of life
II. During the first or second week
conditions! Like neonatal hemochromatosis, galactosemia, tyrosinemia and maple syrup urine
III. After the Third week :
Conditions like! Alpha1 antitrypsin deficiency, Niemann Pick disease, and bile acid synthesis
defects usually present

5. Physical examination
oExamine general body habitus for any dysmorphism Any coarse facial features
micro–or macro -cephaly should alert the physician of any possible IMD.
oHair and skin should be examined for any signs! Of alopecia, eczema,
hypopigmentation, gingival hyperplasia, xanthomas, edema, hirsutism
oExamine! eyes for presence! Of any cataract, corneal! opacities, Kayser
Fleischer ring or lens dislocation
oLook for any evidence of hepatosplenomegaly & Complete neurological &
Musculo skeletal examination

6. Laboratory Evaluation of IMDs
Initial Lab Testing
Blood Complete picture
Plasma glucose levels
Arterial blood gases
Plasma ammonia
Plasma lactate levels
Liver function tests
Electrolytes,
urea and creatinine
Examination! Of the urine including! Color, odor, dip stick, and presence! of
ketones/reducing substances

7. . Specialized Laboratory testing
o Plasma amino acids by HPLC
o Urine Amino acids analysis
o CSF amino acid analysis
o Urine organic acids
o Skin, skeletal muscle, or liver biopsy for enzyme assay
o Brain MRI to assess! For leukodystrophy or basal ganglia changes found in
lysosomal storage or mitochondrial disorders respectively

8. HYPOGLYCEMIA HYPER AMMONIA . CONGENITAL
HYPOTHYRODISM

9. HYPOGLYCEMIA
o Hypoglycemia typically occurs in fatty acid oxidation disorders (such as medium chain
acyl CoA dehydrogenase deficiency),glycogen storage diseases (GSD),gluconeogenic
disorders, galactosemia ,and hereditary fructose intolerance. It also may occur in amino
acid disorders, organic acidemias, and mitochondrial disorder
o Hypoglycemia associated with IMDs usually presents with hepatomegaly.
o. In patients which present with hypoglycemia but without permanent liver
enlargement look for the presence or absence of ketosis and metabolic acidosis.

11. HYPER AMMONIA
oA plasma Ammonia level should! be obtained! For any child with unexplained
vomiting, lethargy, or other evidence of an encephalopathy.
oHyperammonemia is a characteristic finding in urea! Cycle defects, organic
acidemias, fatty acid oxidation defects, and liver dysfunction
oIn patients with raised ammonia levels, look for the presence or absence! Of
metabolic acidosis
oThose with metabolic acidosis and Raised lactate! levels may be suspected of
having pyruvate Metabolism Defects or mitochondrial respiratory chain Defects,
while those with abnormal urinary organic acid levels may be having organic
acidemias.

13. CONGENITAL HYPOTHYRODISM
oInability of thyroid gland to produce thyroxine (T4)
oEarly detection & treatment is necessary to avoid mental retardation
oIncidence in 1;2000 births
oIn normal babies there is a surge of TSH production in the first 24 hours and a
return to normal by five days of age.
oMost babies with congenital hypothyroidism have serum concentrations in
excess of 200 mU/L (normally

14. CONGENITAL HYPOTHYRODISM
False positive :
prematurity ,collection prior to 24 hours (TSH Spikes )
False negative :
critically ill & Post transfusion
Children affected by congenital hypothyroidism are treated by
thyroxine replacement therapy.

17. Reporting results
o New born screening is NOT Diagnostic
o New born screening is NOT Comprehensive
o The disorder detected by new born screening represents only small fraction of all inborn
error of metabolism
o Normal & abnormal results
oUnsatisfactory specimen results
testing is performed & results are reported with note that specimen was unsatisfactory
oRepeat collection is required

18. Reporting Abnormal Results
Presumptive (definite) positive
High Probability that infants have disorder
recommended referral to appropriate medical specialist for counseling & repeat screen
or confirmatory test
Suspected (borderline) abnormal
Screening was slightly abnormal ,infants needs medical evaluation & repeat testing
Repeat/confirmation of abnormal test results is situation of urgency

21. Thank you