1. The document discusses newborn screening, which primarily detects inborn errors of metabolism and genetic disorders that can be treated if detected early. 2. The mandatory newborn screening tests in the Philippines screen for 5 conditions: congenital adrenal hyperplasia, congenital hypothyroidism, phenylketonuria, galactosemia, and G6PD deficiency. 3. Each condition is described in 1-2 sentences, including what it is, how it is tested for in newborns, and its potential consequences if untreated. The document provides brief but comprehensive overviews of the key genetic disorders included in newborn screening.

1. NEW BORN SCREENING
PRENATAL TESTING
• DNA based diagnostic tests
• F >35 ↑ risk for development of genetic disease
1. Ultra sound – easiest to perform
2. Chromosomal analysis (karyotyping)
• i.e. suspected Trysomi 21 defect (Down’s syndrome)
• Sample of choice: amniotic fluid, chorionic villi sample (CVS)
NEONATAL SCREENING
• Primarily to detect disorders in which immediate treatment can prevent
catastrophic consequences.
• Detects mostly inborn errors of metabolism
• Routine neonatal tests chosen are based mainly on the epidemiology,
depending what chromosomal abnormalites are present or prevalent in a
given area.
• In the Philippines, according to REPUBLIC ACT 9288 there are 5
GENETIC DISEASES or INBORN ERRORS of METABOLIS that every
new born MUST be tested for:
1. Congenital Adrenal Hyperplasia (CAH)
2. Congenital Hypothyroidism (CHT)
3. Phenylketonuria (PKU
4. Galactosemia
5. G6PD Deficiency
• If a child has family Hx of a specific chromosomal abnormality, the lab
must be notified to include the specific test for that particular abnormality
in the screening process.
• Most of the neonatal screening tests are tests for metabolic disorders.
• FALSE NEGATIVE RESULTS may occur for some screening tests for
some diseases of the following diseases if specimen from newborn is
taken LESS THAN 24 hrs after birth: congenital hypothyroidism,
homocystinuria, tyrosemia, cystic firosis.
• The following tests may be performed on infants who appear clinically well
in the 1st 24 hrs but develop signs of illness on the 2nd or 3rd day:
o CBC – to test for any red cell or other hematological abnormalities
o Blood gases- to test for metabolic acidosis or alkalosis
o Urinalysis- to test for ketonuria
o Blood lactate level – to test for lactic acidosis
o Blood ammonia level
o Liver function test
o PT, PTT
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2. 1. Congenital Adrenal Hyperplasia (CAH)
• Synonym: adrogenital syndrome
• All variants are autosomal recessive.
• Most common variants: Type I and Type II
• Most common cause (95%): 21-hydroxylase deficiency
• Types I, II, and III - block formation of corticosterone, and cortisol
o Abnormally ↑ androgen hormone production
Male ♂ Female ♀
In Utero enlargement of genetalia ambiguous female
(pseudohermaphtoditism (macrogenitosomia genetalia
) praecox)
Masculization of external
gentalia
After Birth precocious puberty virilization
Atypical variants ambiguous female Unaffected
Type IV, V , and VI gentalia
• Type II, IV, and VI –
o causes a salt losing crisis similar to that seen in Addison’s disease.
o Blocks the mineralcorticoid pathway
• Methods/tests used to detect 21 hydroxylase deficiency:
o Measuring the level of 17-OHP (hydroxypregnenolone)
o Genotyping the blood of the newborn
• Tx: glucocorticoid or mineralcorticoid replacement
• Goals of Tx:
o Children: normal growth, normal height, and pubertal development
o Adult:
 lessen signs of virilization and resume fertility
 ↓ ACTH to <100 ng/L
 ↑ 17-OHP (hydroxypregnenalone) to100-1000 ng/dL
2. Congenital Hypothyroidism (CHT)
• Most common preventable cause of mental retardation.
• Early detection is critical for the prevention of the severity of mental
retardation associated with hypothyroidism.
• Untreated CHT leads to mental retardation.
• Prevalence: 1 in 3000 – 5000 births. Sometimes higher depending on the
ethnicity and/or deficiency of iodine.
o 85% - due to agenesis (failure of development of thyroid gland) – most
common cause.
o 10% - due to defect in enzymes of thyroid hormone synthesis
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3. o 95% - are PRIMARY
o 3-5% - are SECONDARY as a result of a pituitary disorder or a
malfunction of the hypothalamus
• Fetal Screening for CHT:
o Specimen used: dry blood spot on fetal screening card or cord serum
o Test for BOTH T4 and TSH.
• Result: ↓T4 and ↑TSH = HYPOTHYROIDISM
• If ONLY T4 tested - may miss compensated hypothyroidism.
• 15% of infants with a PRIMARY thyroid disorder have a
normal T4 (compensated) and an ↑TSH.
• If ONLY TSH tested – may miss hypothyroidism due to pituary disorder or
hypothalamic malfunction.
• FALSE ↓T4 may occur due to:
1. Very low birth weight (VLBW) infants
o T4 must be re-tested on 2nd and 4th-6th week for late onset of
transient hypothyroidsm.
2. Congenital absence of thyroid binding globulin (TBG)
• TSH is MORE sensitive than T4 in testing for hypothyroidism.
o LAB RESULT INTERPRETATION
• TSH = <10 meq/L – NO further action needed
• TSH = 10-20 meq/L – must repeat test in 2-6 weeks
• TSH = >20 meq/L – Dx with CHT
3. Phenylketonuria (PKU)
• It is an autosomal recessive genetic disorder.
• Characterized by a deficiency in hepatic enzyme phenylalanine
hydroxylase.
• Phenylalanine hydroxylase in needed to convert amino acid
PHENYLALANINE to amino acid TYROSINE.
• Phenylalanine hydroxylase DEFICIENCY leads to PHENYLALANINE
ACCUMULATON in the body.
• Excess PHENYLALANINE in the body is CONVERTED to
PHENYLPYRUVATE (also known as PHENYLKETONE)
• PHENYLKETONE is detected in the URINE.
• ACCUMULATION of phenylalanine in the body leads to MENTAL
RETARDATION.
• At birth, infant serum phenylalanine level = <2mg/100mg due to maternal
enzymes.
TESTING FOR PKU
1. Urine Phenyl Ketonurina Test or Ferric chloride Test
• Detected 3-6 weeks
2. Blood Test/s
• HPLC
• Guthrie Test
• Detects > 4mg/100ml
• Test for both phenylalanine and tyrosine levels
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4. • Typical (+) PKU patient:
o ↑Phenylalanine = >15mg/100mg
o ↓Trosine = <5mg/100mg
• Ideal time to collect PKU specimen = after 48hrs (24-48 hrs after infant
started breastfeeding or formula feeding)
• If specimen taken <24 hrs of birth – have baby brought back for retest
• If PKU result within normal range – have baby come back 1 to 2 weeks for
confirmatory recheck.
• Tx: low protein (especially phenylalanine) diet and avoid foods that contain
aspartame (it contains phenylalanine).
4. Galactosemia
• Autosomal recessive genetic disorder
• Unable to convert galactose to glucose
• Found in 1 out or 62,000 born infants
• Most common cause: Deficiency in galactose-1-phosphate uridyl
transferase (GALT) – causes Classic Galactosemia
o Deficiency in GALT enzyme leads to ↑ galactose accumulation in
blood
o Some symptoms: hypoglycemia, vomiting, diarrhea, irritability,
feeding difficulty, failure to thrive, jaundice, hepatomegaly, easy
bruisability, lethargy, cataract, premature ovarian failure, brain
damage, cirrhosis.
o Duarte galactosemia is a variant of classical galactosemia. Mostly
asymptomatic.
o Dx by demonstrating galactose in blood and urine
 2/3 of patients with galactosemia - test (+) for galactose
 Copper sulfate reducing test (Clinitest)
 Glucose oxidase test
• 2 Other Enzyme Deficiencies that cause Galactosemia
o Galactokinase (GALK) Deficiency
 May cause cataracts in infants
o Galactose Epimerase (GALE) Deficiency
 Also known as GALE deficiency, Galactosemia III and UDP-
galactose-4-epimerase deficiency
 There are 2 forms of epimerase deficiency: benign RBC
deficiency and Severe liver deficiency. Severe form is
similar to galactosemia
• Screening Tests:
o Pager (sp?) Assay
 Milk or formula feeding necessary to perform.
o Beutler’s Fluorometric Method
 Milk or formula feeding NOT necessary to perform.
 Does NOT detect galacto kinase deficiency but DOES detect
the Duarte galactosemia variant.
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5. • Other Lab Test to aid in Dx:
o AST and ALT (included in LFT) – liver enzymes will be ↑
o Histologically: biopsy reveals fatty metamorphosis as early as 3
months of age.
• Tx: Restriction of galactose in the diet.
5. G6PD Deficiency
• Out of the 5 components of the NBST, this is the only disorder that is X-
linked.
• Affects males more than females.
• Mostly among Caucasian with Kurdish Jewish people with the highest
Incidence.
• Also common in the Middle East, the Mediterranean, and Asia.
• G6PD is seen in the pentose phosphate pathway of the RBCs. It’s plays a
role of glucose metabolism in the RBC.
• Abnormal hemolysis in G6PD deficiency can manifest in a number of
Ways:
o Prolonged neonatal jaundice possibly leading to kernicterus
o Hemolytic crises in response to:
 Illness (especially infections)
 Certain drugs: antimalarial, sulfa drugs, nitrofurontoin, apirin,
and analgesics similar to aspirin like phenacetin.
 Certain foods: most notably fava beans (favism)
 Certain chemicals
 Diabetic ketoacidosis
o Very acute crisis can cause acute renal failure
• Dx Test:
o Peripheral Blood Smear
• Look for the following features:
o Poikilocytosis, spherocytes, and Heinz bodies.
o Heinz bodies – precipitate seen when hemoglobin is
Denatured. Special stains are used like methyl violet and
Crystal violet
o Other screening tests: Methemoglobin Test, gluthathione stability
test, dye reduction test, ascorbic acid test, fluorescent spot test,
G6PD assay.
 False normal result with African Americans: GTS and DRT.
 G6PD assay - Invalid result if patient transfused:.
6. Trisomy 21 (Down’s Syndrome)
7. Cystic Fibrosis
8. Amino Aciduria
9. Lysosomal Storage Disorder
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