Metabolic Newborn Screening Lecture Flashcards
List and understand the criteria used in selecting disorders for newborn screening:
Disease should be severe or have potential for severe consequences
Natural history of the disease should be understood
Effective treatment generally available and dependent on diagnosis
Disease incidence high enough to warrant screening
Screening test should have reasonably good sensitivity and specificity
Screening test should be used by entire at-risk population
Adequate system for follow-up for positive results should be provided
Economic cost-benefit analysis should favor screening and treatment
Tandem Mass Spectrometry
Measurement of mass to charge ratio of charged particles.
Understand the basic groups of metabolic disorders identified by the newborn screen
Amino Acid Disorders: Phenylketonuria, Maple Syrup Urine Disease, Homocystinuria, Tyrosinemia, Type I, Arginosuccinic aciduria, Citrullinemia
Hb electrophoresis HbS, HbSC, HbS/Beta-thal
Fatty Acid Disorders: MCAD, VLCAD, LCHAD, Trifunctional Protein Deficiency, Carnitine Update Defect
Organic Acidemias: Isovaleric, Propionic, Methylmalonic, Glutaric, 3-methylcrotonyl CoA, Beta ketothiolase, HMG CoA lyase
Other: Hypothyroidism, Biotinidase Deficiency, Congenital Adrenal Hyperplasia, Galactosemia, Cystic Fibrosis, Hearing, Critical Congenital Heart Defects
Phenylketonuria (PKU)
(inheritance pattern, mutated gene, symptoms, treatment)
Phenylketonuria (PKU):
Autosomal recessive, results from mutation in phenylalanine hydroxylase gene.
Infants normal at birth but over time develop microcephaly, seizures, mental impairment, eczema, loss of pigmentation.
Reducing/Eliminating phenylalanine promotes normal life
Guthrie Test
Guthrie test was first test available for newborn screening. Screens for PKU.
Blood spot discs added to bacterial cultures which have an inhibitor added.
Phenylalanine, phenylpyruvate, and phenyllactate will restore growth of the bacteria.
Galactosemia
Defect in Galactose-1-Phosphate uridyl transferase. AR, 1 in 62,000 births.
Infants will present with emesis, diarrhea, jaundice, and E. coli sepsis, liver and kidney dysfunction, cataracts
Eliminate Galactose from the diet
MCADD: Medium-chain acyl CoA dehydrogenase deficiency
MCADD: Medium-chain acyl CoA dehydrogenase deficiency
AR, 1 in 2000,
Lethargy, hypoglycemic crisis, coma, and seizures
The first episode is fatal in up to 25% of cases
Give the baby sugar
Confirm the findings on newborn screen. False positives do occur!
Continue other appropriate treatments. Commonly patients who present early in life with metabolic disorders are also treated for infections. That’s fine!
IVA: Isovaleric Aciduria
IVA: Isovaleric Aciduria
A defect in Isovaleryl-CoA dehydrogenase
AR, 1/100,000
Patients can present with metabolic acidosis, hyperammonemia, hypoglycemia, decreased WBC and platelets. They may also have the odor of sweaty feet
Krabbe Disease
Not currently screened
Autosomal recessive condition which is usually characterized by infantile-onset progressive neurologic disease (90% of cases)
The other 10% present between age 1-50 years
Only supportive care available for symptomatic patients
Diagnosis: A diffuse leukodystrophy caused by galactocerebridase deficiency
Infantile form presents in first 2-3 months: Extreme irritability, Spasticity, Developmental Regression, Peripheral neuropathy, 85-90% die before two years of age
Treatment: Only supportive care is available to control irritability and spasticity in symptomatic children, Hematopoetic Stem Cell Transplantation in presymptomatic infants may improve and preserve cognitive function, The results of transplantation have been decidedly mixed
History of Newborn Screening
Deaths have decreased from 160 to 5.9/1000 since 1900.
Most common causes of infant mortality 2015:
Congenital Anomalies, deformations, and chromosomal abnormalities (23.8%)
Extreme Prematurity (19.4%)
Sudden Infant Death Syndrome (17.3%)
Maternal Complications of Pregnancy (10.5%)
Accidents and Injuries (4.2%)
Causes of the drop in mortality: Presence of antibiotics, vaccines, nutrition, education, sanitation
Proactive treatment results in decreased cost and better outcomes than reactive treatment.
Newborn Screening Results
(Slightly abnormal, Highly abnormal)
NBS Results:
Slightly abnormal
Usually only one or maybe a couple of analytes are abnormal and may be in predictable pattern (TPN, prematurity, etc)
Lab notifies provider and NBS is redone
Highly abnormal
Metabolites far above cutoff, possibly multiple metabolites
Lab notifies PCP and metabolic specialist
Dealing with NBS Results
(Galactosemia as example)
Dealing with NBS Results:
1) Contact – Family right away
2) Consult – Metabolist on call
3) Evaluate – For GALT, see baby right away, examine for signs and symptoms of galactosemia, repeat GALT, Gal, Gal-1-P levels
4) Manage – Change to galactose free formula
Future of NBS Tests
SCID testing has been recommended by NBS advisory committee and most states are implementing
Pulse Oximetry for Congenital Heart Disease
Recommended by HHS Secretary Sebelius in 2011
Lysosomal Diseases
Other states (Like Missouri) have adopted NBS for Hurler/Hunter, Fabry, Krabbe, others
Utility of testing less clear
