Pediatrics - Newborn Screening

Front 1

In Oklahoma, what conditions are included in the newborn screening?

Back 1

PKU, congenital hypothyroidism, classic galactosemia, sickle cell disease, cystic fibrosis, congenital adrenal hyperplasia, MCAD, biotinidase deficiency, maple syrup urine disease, homocystinuria, amino acid disorders, fatty acid oxidation disorders, organic acid disorders

Front 2

What is the purpose of the newborn screening?

Back 2

Early recognition of disorders and intervention can eliminate or reduce mortality and morbidity.

Front 3

What disorders are included in screenings for all 50 states?

Back 3

PKU and congenital hypothyroidism

Front 4

What is NBS?

Back 4

An universally accepted public health program that integrates sample collection, lab testing, follow up, diagnosis, treatment of the identified disease and tracking of outcomes.

Vary from program to program depending upon state statutory and regulatory structures.

Front 5

What are the limitations of NBS?

Back 5

A positive test always needs to be confirmed.
If a test is positive, the disorder may NOT be present.
High sensitivity results in increased false positives, resulting in lower specificity.
If a test is negative, the disorder may be present.
Need to monitor infant and look for signs and symptoms of disorders.

Front 6

Phenylketonuria (PKU)

Back 6

- Autosomal recessive disorder
- Excessive build-up of phenylalanine
- Decreased activity of phenylalanine hydroxylase (enzyme that coverts phenylalanine to tyrosine)
- On a normal neonatal diet, infants develop hyperphenylalaninemia.
Incidence- 1:10,000 live Caucasian births
Confirmed cases in OK from 1991-2005 = 36

Front 7

S/S of PKU

Back 7

Non-fatal
Severe mental retardation (MR)
Hyperactivity
Spasticity
Seizures
Eczema and light skin pigmentation
Urine has “mousey odor”
Autistic-like behavior
--- S/S can be seen in as little as two weeks.

Front 8

Diagnosis of PKU

Back 8

Perform test 24h after birth
- If screened <24h, rescreen by 2 weeks of age
Work-up of abnormal results:
- Serum phenylalanine
- Serum tyrosine

Front 9

Treatment of PKU

Back 9

Dietary Restriction of phenylalanine
Monitor levels
Treatment and follow-up guidelines
Late Treatments
- Will not reverse MR
- May cause improved behavior control

Front 10

Follow-up of PKU

Back 10

Management by team
- Physician, metabolic or clinical geneticist, nutritionist, genetic counselor
Immediate dietary therapy and supplemental tyrosine.
Monitoring of amino acids, growth and development and diet with adjustment of Phe/Tyr needs.
1st year follow-up
- Regular visits to treatment centers
- Weekly Phe/Tyr levels for the 1st month
- Biweekly to triweekly levels for the 1st 2 years of life
Goal: Phe at <6mg/dL

Front 11

What is a hallmark symptom of PKU?

Back 11

Urine has "mousey odor"

Front 12

Causes of Congenital Hypothyroidism (CH)

Back 12

Agenesis or ectopic thyroid (85%)
Hormonogenesis disorder (10-15%)
May be autosomal recessive trait
Pituitary or Hypothalamus defects (<5%)

Front 13

When does treatment of PKU begin?

Back 13

Elevated >20 mg/dl on regular diet, with normal to low serum tyrosine levels and normal urine pterins
Treatment started immediately

Treatment is initiated when levels consistently exceed >10 mg/dl

Front 14

What is the most common neonatal metabolic disorder?

Back 14

Congenital Hypothyroidism (CH)
Incidence: 1: 3,000 to 1: 4,000 in the U.S.

Front 15

Pathophysiology of CH

Back 15

Hypothalamic-pituitary-thyroid axis
- Functions at 20 weeks
- Matures by birth
Appear normal at birth
- Protected by placental transfer of maternal thyroid hormone
- Even with congenital absence of the thyroid gland, most newborns appear normal at birth and gain weight normally for the first 3-4 months of life

Diagnosis should be based on newborn screening and not on abnormal physical findings

Front 16

S/S of CH

Back 16

Mental retardation
- Mean IQ = 80
Poor growth
Large tongue, hoarse cry
Facial puffiness, goiter
Low metabolic rate
- Bradycardia, constipation, lethargy
Poor peripheral circulation

Front 17

Testing of CH

Back 17

Assess:
- serum T4 (thyroxine) - decreased
- TSH (thyroid-stimulating hormone) - increased
10% of cases are detected at a 2nd screening at 2-6 weeks

Front 18

Treatment of CH

Back 18

Levothyroxine
- start in first weeks of life
Monitor growth and development monthly
Frequent lab evaluations
Follow-up with pediatric endocrinologist

Front 19

Galactosemia

Back 19

Autosomal recessive disorder
Inability to metabolize galactose
Build up of galactose-1 phosphate in the liver and renal tubules and progresses to Faconia syndrome
Incidence 1:40,000 live births
In OK from 1991-2005, 11 total cases

Front 20

What is the classic cause of galactosemia?

Back 20

Deficiency of galactose-1-phosphate-uritransferase (GALT), enzyme that breaks down galactose

Front 21

S/S of galactosemia

Back 21

Within 2 weeks:
- vomiting
- lethargy,
- jaundice
- hepatosplenomegaly
- cataracts
- failure to thrive (FTT)

Front 22

Complications of galactosemia

Back 22

E. coli sepsis may result
Can be fatal as a result of liver failure, sepsis or bleeding.
If survived, child may have cognitive and developmental disabilities.

Front 23

What comprises Fanconi Syndrome?

Back 23

Results from untreated galactosemia, S/S may occur in little as one month.
- Cataracts
- Hepatic cirrhosis
- E. coli sepsis may result - can be fatal

Front 24

Diagnosis of galactosemia

Back 24

Plasma galactose - high
RBC galactose-1-phosphate - high
- Needs to be measured after milk ingestion
Galactose-1-phosphate uridyl transferase
- Low in classic galactosemia
- Can be measured at any time
Renal Tubular Dysfunction
- Galactosuria, proteinuria, aminoaciduria
Liver Dysfunction
- Elevated conjugated and unconjugated bilirubin, elevated LFTs (liver function tests), coagulopathy

Front 25

Treatment of galactosemia

Back 25

Galactose-free diet ASAP and continued through life
Lactose-free diet
Calcium supplementation

Front 26

Sickle Cell Disease, Hemoglobinopathies

Back 26

Affects RBC
Inherited defects of hemoglobin
Substitution of valine for glutamine on beta globin chain
Alters structure of Hgb molecule

Front 27

Etiology of hemoglobinopathies

Back 27

Autosomal recessive disorders

Single abnormal gene (heterozygotes) have a hemoglobin trait and are carriers

Front 28

Pathophysiology of hemoglobinopathies

Back 28

2 abnormal genes (homozygotes) have the disease
3 major types:
- HgbSS - sickle cell disease
- HgbSC - combined heterozygosity for Hgb S and Hgb C
HgbS - thalassemia (sickle cell beta thalassemia)

Front 29

Incidence of hemoglobinopathies

Back 29

1 out of 400 African American infants
8% of African Americans have sickle cell trait

Front 30

S/S of hemoglobinopathies

Back 30

Symptoms evident by 6 months
Lifelong hemolytic anemia
Splenic sequestration of RBCs
Vasoocclusive events
- Dactylitis (pain in hands and feet)
–-- most common initial symptom of disease
- Aseptic necrosis
- Leg ulcers, priapism
- CVA
- Acute Chest Syndrome
Aplastic crises
Sepsis

Front 31

What is the most common initial symptom of hemoglobinopathies?

Back 31

Dactylitis
- Pain in hands and feet due to occlusion in vessels

Front 32

Treatment of hemoglobinopathies

Back 32

Penicillin prophylaxis (to prevent sepsis)
- 125mg BID by 2months of age for SS or S
- 250mg BID starting age 2 until 5
- May consider d/c prophylaxis at age 5
Pneumococcal vaccine in addition to regular vaccinations
- At 2 and 5 years of age
Hydroxyurea
Consultation with pediatric hematologist or sickle cell center

Front 33

Complications of hemoglobinopathies

Back 33

Febrile illness
- Hospital admission
- Blood cultures
- Broad-spectrum parenteral antibiotics
Infection is the most common cause of death
- Children- respiratory infections
- Adults- underlying chronic organ injury infections

Front 34

Congenital Adrenal Hyperplasia (CAH)

Back 34

Autosomal recessive disorder
21-hydroxylase deficiency
Abnormalities in adrenal steroidogenesis - impaired cortisol production - increased ACTH secretion - adrenal hyperplasia - increased production of androgens
Incidence is 1/15,000 births

Front 35

Clinical features of CAH

Back 35

Masculinization of female genitalia, early virilization in boys, early accelerated growth.
In more severe cases, the infant develops a salt-losing crisis in 2-4 weeks of life.
- Hypovolemia
- Hyponatremia
- Hyperkalemia

Front 36

Treatment of CAH

Back 36

Glucocorticoids
side effect - Cushing's syndrome

Mineralcorticoids
side effects - HTN and hypokalemia

Surgery - female genital reconstruction

Front 37

Medium-chain Acyl-CoA Dehydrogenase Deficiency (MCAD)

Back 37

Fatty acid oxidation disorder
Clinical manifestations develop when healthy appearing infants that do not eat for a prolonged period or have increased energy requirements have impaired fatty acid oxidation leading to fatty acid buildup.
- Hypoketotic hypoglycemia
- Hyperammonemia
- Hepatomegaly
- Splenomegaly
- Sudden death
--- Could this be partially responsible for SIDS?

Front 38

Management of MCAD

Back 38

No cure
Prevent hypoglycemia
Do not go long periods of time without food (10-12 hours)
- Provide carbohydrate rich snack before bed

Front 39

Cystic Fibrosis

Back 39

Autosomal recessive disorder of exocrine glands
13% mortality rate among infants
Growth retardation, FTT, malabsorption – pancreatic insufficiency, pulmonary infections

Front 40

Treatment of CF

Back 40

Pancreatic enzyme replacement
Fat soluble vitamins
Bronchodilator therapy
Treatment of lung infections

Front 41

Why should a newborn hearing screening be performed?

Back 41

Normal hearing is essential for normal language development
Significant bilateral hearing loss is present in 1-3 infants/1000
With early remediation by 6 months, language and social development are consistent with physical development

Front 42

Risk factors of hearing loss

Back 42

Admissions to NICU for more than two days
Congenital syndrome
Family history of hearing loss
Craniofacial abnormalities
Hyperbilirubinemia

Front 43

What procedure should be followed if a newborn is discharged from the hospital early?

Back 43

Decreased reliability in screening results when discharged early (<24h)
Recommended to draw close to discharge time, but no later than 7 days.
If specimen collected before 24h, get repeat screen within 2 weeks.

Front 44

What is the role of the PA regarding newborn screenings?

Back 44

Discuss NBS with parents
Document results
- To ensure tests were performed correctly
Order a second test if discharged <24h
Rely on physical findings
- Do not assume that a negative test result means that there is no disease!