COMMON NEWBORN SCREENING TEST

CONGENITAL HYPOTHYROIDISM (CH)

Endocrine disorder also referred to as cretinism / dwarfism; due to absence or lack of development of thyroid gland causing lack of thyroxine needed for metabolism and growth.

Transient CH

– often associated with maternal Graves disease treated with antithyroid drugs.

sporadic (nonhereditary);

CH Majority of cases are about 15% are autosomal dominant.

thyroid dysgenesis.

CH Most common pathogenesis:

iodine deficiency.

CH Worldwide most common cause:

Severe deficiency

CH Severity: = early manifestations;

mild deficiency

CH Severity: = delayed symptoms (months to years later).

CH Importance of Early Treatment

• Early detection and treatment are critical.

• Delay causes cognitive impairment;

• IQ loss is directly related to delay in treatment initiation.

0–3 months

CH: IQ Outcomes by Treatment Timing : mean IQ 89 (range 64–107)

3–6 months:

CH: IQ Outcomes by Treatment Timing; mean IQ 71 (range 36–96);

after 6 months:

CH: IQ Outcomes by Treatment Timing: mean IQ 54 (range 25–80).

Higher

CH Prevalence by ethnicity: in Hispanic and American Indian/Alaskan Native (1 in 2000–1 in 700);

lower

CH Prevalence by ethnicity: African Americans (1 in 3200–1 in 17,000).

Special Risk Groups (CH)

• Infants with Down syndrome (~1 in 140 risk);

• higher incidence of congenital abnormalities;

• preterm infants may have transient hypothyroxinemia;

• infants <28 weeks may need temporary hormone replacement.

Untreated CH Effects

• Jaundice,

• feeding,

• hypotonia,

• macroglossia,

• coarse facial features,

• mental retardation,

• short stature.

Neonatal screening

CH Diagnostic Evaluation: – initial filter paper blood spot

TSH

CH Diagnostic Evaluation: Neonatal screening – initial filter paper blood spot T4; if low T4 measure __;

2–6 days of age

CH Diagnostic Evaluation: Neonatal screening – initial filter paper blood spot T4; best screening at __;

24–48 hours or before discharge

CH Diagnostic Evaluation: Neonatal screening – initial filter paper blood spot T4; Usually done at

low T4 (<10%) + high TSH (>40 mU/L).

CH Diagnostic Evaluation: Neonatal screening – initial filter paper blood spot T4; abnormal values: → further testing required

Additional Tests for CH

• Serum T4, T3, resin uptake, free T4, thyroid-bound globulin;

• thyroid scan and uptake using radioactive iodine

low protein-bound iodine, T4, T3, free T4; ↓ iodine uptake

CH diagnostic findings:

○ Skeletal radiography for bone age

○ Thyroid values are normally higher in newborns than older children

○ Preterm/sick infants may have lower values

○ Repeat T4 and TSH after 30 weeks corrected age or after illness resolution

CH diasgnostic Other evaluations

Skeletal radiography

CH diasgnostic Other evaluations: for bone age

Preterm/sick infants

CH diasgnostic Other evaluations: may have lower values

30 weeks corrected age or after illness resolution

CH diasgnostic Other evaluations: Repeat T4 and TSH after

newborns

CH diasgnostic Other evaluations: Thyroid values are normally higher in ___ than older children

levothyroxine sodium (Synthroid, Levothroid);

CH Treatment: Lifelong thyroid hormone replacement; drug: __ Target TSH 0.5–2.0 mU/L during first 3 years of life

○ Regular thyroxine levels

○ Bone age surveys to ensure optimal growth

CH Drug Monitoring:

CH Nursing Care: Priority:

Early identification, screening compliance

○ Especially in preterm, early discharge, and home-born infants .

○ “Quiet and good” baby

○ Prolonged jaundice, constipation, umbilical hernia

CH Nursing Care: ● Clinical suspicion signs:

can be crushed and added to formula, water, or food

CH Nursing Care:● Medication administration: Tasteless →

double dose next day

CH Nursing Care:● Medication administration: Missed dose →

■ Rapid pulse, dyspnea, irritability, insomnia, fever and sweating, weight loss

CH Nursing Care:● Medication administration: Signs of overdose

■ Fatigue, sleepiness, decreased appetite, constipation

CH Nursing Care:● Medication administration: Signs of inadequate treatment

PHENYLKETONURIA (PKU)

Inborn error of metabolism due to lack of enzyme phenylalanine hydroxylase; a

● Autosomal recessive inborn error of metabolism

○ PAH gene on chromosome 12q24

○ Deficiency/absence of enzyme metabolizing phenylalanine

PAH gene on chromosome 12q24

PKU ● Autosomal recessive inborn error of metabolism

Classic PKU

is part of hyperphenylalaninemia spectrum ○ Discussion limited to severe classic form

Phenylalanine accumulates in blood; phenyl acids excreted in urine; phenylacetic acid causes musty odor; tyrosine deficiency leads to fair features - Increased eczema and dermatologic problems

PKU Pathophysiology

■ Phenylacetic acid

PKU Metabolites: → musty urine odor

■ Phenylpyruvic acid

PKU Metabolites: → term “phenylketonuria”

Tyrosine deficiency

PKU

– Needed for melanin, epinephrine, thyroxine

■ Results in blond hair, blue eyes, fair skin

■ Increased eczema and dermatologic problems

U.S.:

PKU Prevalence: 1 in 15,000 births

Europe:

PKU Prevalence: 1 in 10,000;

Asia/Africa.

PKU Prevalence: low in

PKU Clinical Manifestations (untreated)

• Failure to thrive,

• Frequent vomiting,

• irritability,

• hyperactivity,

• Erratic, Unpredictable Behavior

■ Phenylalanine accumulation

■ ↓ dopamine and tryptophan

■ CNS damage: defective myelination, gray/white matter degeneration, cortical lamination disturbance

PKU Clinical Manifestations (untreated): Cognitive impairment due to:

■ bizarre behavior, screaming, fright reactions

■ head banging, arm biting

■ disorientation, catatonia-like positions

PKU Clinical Manifestations (untreated): Older children:

Guthrie blood test (Bacillus subtilis growth)

PKU Diagnosis: detects phenylalanine >4 mg/dl; Does not quantify levels;

Fresh heel blood only (not cord blood)

PKU Diagnosis: Specimen requirement:

○ Cannot eliminate completely (essential amino acid)

○ Enzyme replacement ineffective

PKU Treatment: Dietary phenylalanine restriction;

PKU Dietary goals: ■ 2–6 mg/dl

(neonates–12 yrs)

■ 2–10 mg/dl

PKU Dietary goals:(adolescents)

■ 2–15 mg/dl

PKU Dietary goals: (adults)

Start ASAP, ideally 7–10 days of age if >10 mg/dl

PKU Therapeutic Management: Treatment timing

○ Individualized phenylalanine intake

○ Phenylalanine-free formulas: Phenex-1, Phenex-2

○ Provides protein, vitamins, minerals, calories

PKU Therapeutic Management: Nutrition therapy

○ Restricted diet + medical foods

○ Regular blood phenylalanine and tyrosine monitoring

PKU Therapeutic Management: Lifelong management

○ Phenylalanine >6 mg/dl causes fetal defects

○ Levels <6 mg/dl recommended ≥3 months before conception

PKU Therapeutic Management: Maternal PKU

Family education on strict diet

PKU Nursing Care:

: ○ Low-phenylalanine foods measured

○ High-protein foods eliminated

PKU Nursing Care: Food management

Aspartame (NutraSweet)

PKU Nursing Care: Avoid:

Solids introduced normally (fruits, vegetables, cereals)

PKU Nursing Care: Feeding progression:

○ Appetite changes

○ Increased independence

○ Poor dietary control in older children

PKU Nursing Care: Challenges:

○ Registered dietitian essential

○ Gram scale food weighing

○ Exchange lists

○ Child involvement in meal planning early

PKU Nursing Care: Support care

○ Paste method to reduce lumps

○ Blender/mixer helpful

○ Travel mixers useful

PKU Nursing Care: Formula preparation

○ Formula bars for adolescents

○ Formula capsules (≥20/day required)

PKU Nursing Care: Alternatives

GALACTOSEMIA

Rare autosomal recessive disorder due to enzyme deficiencies (GALT, GALK, GALE).

(GALT, GALK, GALE).

GALACTOSEMIA Three enzyme deficiencies:

Type 1: Deficient Galactokinase

Types of Galactosemia: – Inability to convert galactose to glucose → galactosemia → galactosuria

mental deficiency, cataracts, death

Type 1: Deficient Galactokinase ■ Complications:

galactose-free diet (avoid milk and milk products)

Type 1: Deficient Galactokinase ■ Dietary treatment:

Type 2: “Classic” Galactosemia

Types of Galactosemia: – Severe deficiency of uridyl transferase (GALT); ~1 in 50,000 births

jaundice, vomiting, hepatosplenomegaly, hypoglycemia, convulsions, feeding difficulties

Type 2: “Classic” Galactosemia: Early symptoms:

liver cirrhosis, irreversible mental retardation

Type 2: “Classic” Galactosemia: Complications:

exclude galactose to prevent liver cirrhosis, mental retardation, cataracts, and recurrent hypoglycemia

Type 2: “Classic” Galactosemia: Dietary treatment:

Galactosemia Pathophysiology

Galactose accumulates causing multi-organ damage (liver, spleen, eyes, brain, GI).

Organ effects: ■ Liver: cirrhosis → jaundice (2nd week) ■ Spleen: enlargement from portal hypertension ■ Eyes: cataracts (1–2 months) ■ Brain: lethargy, hypotonia ■ GI: vomiting, diarrhea, weight loss ■ Infection: E. coli sepsis common

○ Normal at birth

○ Symptoms after milk ingestion

○ High mortality in untreated first month

○ Chronic forms: growth failure, feeding difficulty, developmental delay

Galactosemia Clinical course

■ Hypogonadism

■ Cognitive Impairment

■ Growth Restriction

■ Verbal And Motor Delays

Galactosemia Prognosis ○ Long-term complications even with early treatment:

■ Enzyme Enhancement

■ Metabolite Replacement

■ Gene Therapy

Galactosemia Prognosis: Future therapies needed:

○ History and physical exam

○ Galactosuria

○ ↑ blood galactose

○ ↓ GALT in erythrocytes

Galactosemia Diagnostic Evaluation: Based on

○ hypoglycemia, jaundice, hepatosplenomegaly

○ sepsis, cataracts, hypotonia

Galactosemia Diagnostic Evaluation: Findings

○ Eliminate all lactose and milk

○ No breast milk

○ Soy-protein formula recommended by AAP

○ Elemental formula may be beneficial but costly

Galactosemia Treatment: Infant Feeding:

○ Low-galactose foods only

○ Food lists provided to family

Galactosemia Treatment: Diet progression

Monitor hypoglycemia, liver failure, bleeding, sepsis

Galactosemia Treatment:Supportive care:

GLUCOSE-6-PHOSPHATE DEHYDROGENASE (G6PD) DEFICIENCY

● Deficiency in G6PD; RBC lacks protection from the harmful effects of oxidative substances found in drugs, foods, beverages.

○ Severe anemia and hyperbilirubinemia → kernicterus (jaundice of the brain) and mental retardation, convulsion, coma and even death

○ Most common enzyme deficiency worldwide

X-linked disorder

GLUCOSE-6-PHOSPHATE DEHYDROGENASE (G6PD) DEFICIENCY:

■ Common in African, Asian, Mediterranean, Middle Eastern descent

■ ~400 million affected globally

Sulfonamides, quinolones, chloramphenicol, Vitamin K

Oxidative agents leading to hemolysis in G6PD deficiency: Drugs

Mothballs

Oxidative agents leading to hemolysis in G6PD deficiency: ○ Chemicals:

Fava beans

Oxidative agents leading to hemolysis in G6PD deficiency:Food:

Hyperbilirubinemia, acute/chronic hemolysis, may be asymptomatic.

G6PD Manifestations

malaria-endemic regions

G6PD Epidemiology ○ High prevalence in

~10% of Black males

G6PD Epidemiology ○ In U.S.: ○ Possible malaria protection theory

○ G6PD → produces NADPH

○ NADPH protects cells from oxidative damage

○ RBCs highly vulnerable

○ Total deficiency incompatible with life

G6PD Pathophysiology

○ Gene on distal long arm of X chromosome

○ 400 mutations identified

○ Variants: G6PD Mediterranean, G6PD A–

G6PD Genetics

G6PD Mediterranean, G6PD A–

G6PD Genetics: ○ Variants:

○ Fluorescent spot test (no fluorescence = positive)

○ Spectrophotometric analysis

○ PCR testing for mutations

False negatives possible during acute hemolysis

G6PD Diagnosis: Test

avoid oxidative stressors

G6PD Treatment: Main management

Folic acid/iron

G6PD Treatment: may help

● Main management: avoid oxidative stressors

● Severe anemia → possible transfusion

● Splenectomy not recommended

● Folic acid/iron may help

● No proven benefit: vitamin E, selenium

● Ongoing research for protective medications

G6PD Treatment: