1. NEONATAL SCREENING M.Prasad Naidu MSc Medical Biochemistry,
Ph.D.Research Scholar

2. Most Inborn errors of metabolism presenting in the neonatal period are leathal if specific treatment is not initiated immediately.
Specific diagnosis , even in an infant in whom death seems inevitable, is of great importance for genetic counseling of the family.
Every effort should be made to determine the diagnosis while the infant is alive;
A specific diagnosis may be established by measurement of abnormal metabolites in body fluids, by assAy of the specific enzyme activity, or by identification of the mutant gene.

3. In an attempt to standerdize newborn screening programs, the american college of medical genetics (acmg) recommends that every baby born in the united states be screened for a uniform panel of 29 disorders.
The american academy of pediatrics also endorse the recommendation by the acmg

4. Disorders of organic acid metabolism
Disorders recmmended by the acmg task force for inclusion in newborn screening
Disorders of organic acid metabolism
Isovaleric acidemia
2. Glutaric aciduria type 1
3-hydroxy-3-methylglutaric aciduria
Multiple carboxylase defyciency
Methylmalonic acidemia, mutase deficiency form.
3-methylcrotonyl-c0-a carboxylase deficiency
Methylmalonic acidemia, cbl a, & cbl b forms
Propionic acidemia
Beta ketothiolase deficiency

5. Disorders of fatty acid metabolism
Medium chain acyl c0-a dehydrogenase deficiency.
Very long chain acyl c0-a dehydrogenase deficiency.
Long chain l-3-hydroxy acyl c0-a dehydrogenase deficiency
Trifunctional protein deficiency
Carnitine uptake defect.
Hemoglobinopathies
Sickle cell anemia
Hemoglobin s-β-THALASSEMIA
HEMOGLOBIN SC DISEASE.

6. DISORDERS OF AMINO-ACID METABOLISM
PHENYLKETONURIA
MAPLE SYRUP URINE DISEASE
HOMOCYSTINURIA
CITRULLINEMIA
ARGININOSUCCINIC ACIDEMIA
TYROSINEMIA TYPE 1
OTHER DISORDERS
CONGENITAL HYPOTHYROIDISM
BIOTINIDASE DEFICIENCY
CONGENITAL ADRENAL HYPERPLASIA
GALACTOSEMIA
CYSTIC FIBROSIS
HEARING DEFICIENCY.

7. INBORN ERRORS OF AMINO ACID METABOLISM ASSOCIATED WITH PECULIAR ODOUR
INBORN ERROR OF METABOLISM
1. PHENYLKETONURIA
TYROSINEMIA
MAPLE SYRUP URINE DISEASE
GLUTARIC ACIDEMIA
ISOVALERIC ACIDEMIA
URINE ODOUR
MOUSY OR MUSTY
BOILED CABBAGE, RANCID BUTTER
MAPLE SYRUP,
BURNT SUGAR
SWEETY FEET, ACRID
SWEETY FEET, ACRID.

8. Phenylketonuria . 1 : 10,000 Lab diagnosis. Blood phenylalanine
Normal level is 1 mg/dl.
IN PKU, THE LEVEL IS > 20 mg/dl.
URINE PHENYLEKETONES mg / day.
Tandem mass spectroscopy : most reliable, costly.
Guthrie test : rapid screening test
Ferric chloride test
Dna probes

9. Guthrie test : Was developed in 1961 by robert guthrie
It is a rapid screening test
Certain strains of bacillus subtilis need
phenylalanine as an essential growth factor
Bacterial growth is proportional to the
phenylalanine content in the patients blood.
Guthrie was the father of a mentally challenged child.
He developed a rapid screening test for pku

10. Ferric chloride test.
Earlier in 1934, asbjorn folling, a norwegian biochemist introduced the use of ferric chloride test in urine of a mentally retarded child with decreased skin pigmentation & mousy odor of urine.
A transient blue green colour is a positive test.
But this is a less reliable test.

11. Tandem mass spectrometry [ ms-ms ]
Is a technically advanced method in which many compounds are seperated by molecular weight.
The process requires roughly 2 min / sample & can detect 20 or more inborn errors of metabolism.
Blood obtained by heal-prick is applied to a filter paper, four to six circles approximately cm in diameter, allowed to dry in air, & sent to a screening laboratory for analysis.

12. Tsh (thyroid stimulating hormone)
SERUM
Birth-4 d mIU/L
2-20 wk
5 mo – 20 yr
THYROXIN, TOTAL
1-3 D nmol/L
1 WK
1-12 mo
1-3 yr
3-10 yr
10-20 yr
Thyroxin, free
3 d pmol/L
1 yr
10 yr
Adults

13. LABORATERY FINDINGS IN HYPOTHYROIDISM
Triiodothyronine, total .
serum
Newborn nmol / L
1-5 yr
5-10 yr
10-15 yr
Adults
Triiodothyronine, free .
1-3 d nmol / L
6 wk
Adult ( yr )
LABORATERY FINDINGS IN HYPOTHYROIDISM
T3&T4 IN BLOOD
TSH
RESPONSE TO TRH
PRIMARY
DECREASED
EXAGGERATED RESPONCE
SECONDARY
NO RESPONCE

14. Measurement of t3 , t4 & tsh levels in blood by
hypothyroidism.
Assay of hormones.
Measurement of t3 , t4 & tsh levels in blood by
Radio immuno assay ( ria) or elisa
Chemiluminiscent immuno assay ( c.l.i.a )
immunofluorescence

15. Adrenogenital syndrome ( ag syndrome )
There is congenital deficiency of steroid hydroxylases leading to deficient secretion of cortisol.
Since cortisol, the major feedback effector is not present, acth secretion continues leading to congenital adrenal hyperplasia ( cah ).
21 - hydroxylase defyciency :
most common type
Cortisol totally absent
Lack of feedback leads to increased androgen synthesis.
Virilization of female children who develop ambiguous genitelia.

16. Immunoassay for 17- alpha-hydroxy progesterone Normal value : urine
11-hydroxylase deficiency In this condition symptoms are more serious. The hypertensive veriety of ag syndrome manifests & the child may not survive.
NORMAL VALUE OF
CORTISOL : plasma
9 AM – 600 nmol / L
MIDNIGHT –- 130 nmol / L
Immunoassay for 17- alpha-hydroxy progesterone
Normal value : urine
female : 5.5 – 22 μmol / d
MALE : 8 – 22 μmol / d

17. Maple syrup urine disease
Incidence 1 : I lakh.
Deficient decarboxylation of branched chain keto acids
Laboratory findings
Dinitro phenyl hydrazine test (dnph) :
yellow colour indicates positive test
Ninhydrin test
Thin layer chromatography
Hplc
Tandem mass spectrometry

18. GALACTOSEMIA. GALACTOSE-1-PHOSPHATE URIDYL TRANSFERASE DEFICIENCY
HYPOGLYCEMIA
JAUNDICE
MENTAL RETARDATION
GALACTOSURIA
CONGENITAL CATARACT
LACTOSE FREE DIET

19. SICKLE CELL HEMOGLOBIN ( HbS )
GLUTAMIC ACID IN 6TH POSITION----BETA CHAIN HbA CHANGED TO VALINE.
POLIMERIZATION OF HEMOGLOBIN---SICKLE SHAPED RBC’s.
HYPOXIA
ELECTROPHORESIS : HbS less negatively charged.DECREASED MOBILITY TOWARDS POSITIVE POLE.
SICKLING TEST : SODIUM DITHIONITE

20. THANK YOU