What’s New in Newborn Screening

What’s New in Newborn Screening
By:Kathy Tomashitis, MNS, RD
Pediatric Screening Coordinator
Division of Women and Children’s Services, SC DHEC

Newborn Screening Expansion
* Newborn screening began in South Carolina in the mid-1960’s with testing for phenylketonuria (PKU)
* Over the years, the test panel has expanded as improvements in technology occurred and as research indicated benefit of pre-symptomatic detection for specific disorders

Newborn Screening-Why Expand the Test Panel
* Several factors have lead to the current expansion
o Technological advances: increased use of tandem mass spectrometry (MS/MS) in newborn screening applications and improvement in the screening protocol for cystic fibrosis
o NO ADDITIONAL BLOOD NEEDED!
o Improved morbidity/mortality: research supports improved outcomes for pre-symptomatic identification of cystic fibrosis as well as disorders found through MS/MS; research has long recognized benefit of screening for biotinidase deficiency
o Cost benefit: research supports pre-symptomatic identification of fatty acid, amino acid and organic acid disorders found through MS/MS
* SC health care providers support expanded screening
o Survey of all newborn health care providers in SC conducted in 11/00: top three conditions recommended for expansion include cystic fibrosis, LCHADD ( a fatty acid oxidation disorder) and biotinidase deficiency
o Newborn Screening Advisory Committee recommended step-wise expansion to include cystic fibrosis, biotinidase deficiency and disorders found through MS/MS
* Growing awareness in disparity across states in conditions included in newborn screening test panel
* Expansion would provide SC infants with one of the most comprehensive test panels in US
* Consumer groups such as the March of Dimes support expanded test panels

Newborn Screening Expansion
* Current test panel includes screening for PKU, congenital hypothyroidism, galactosemia, congenital adrenal hyperplasia (CAH), medium chain acyl co-A dehydrogenase deficiency (MCADD) and hemoglobinopathies
Newborn Screening Expansion-Cystic Fibrosis
* Cystic fibrosis is a genetic disorder that is found in 1:3500 Caucasian and 1:17,000 African American births
* CF is a recessive genetic disorder. Risk of recurrence is 1:4 with each pregnancy.
* In CF, the pulmonary and gastrointestinal systems are severely compromised.
* Fluids that are normally thin and slippery become thick and sticky
* Infections are treated aggressively
* Chest physiotherapy used to clear lungs
* Pancreatic enzymes used to aid digestion
* Screening will include measurement of immunoreactive trypsinogen (IRT)
* If the IRT is above a set level, a repeat IRT will be requested.
* If the IRT is still above normal limits on the second specimen, the infant will be referred to a CF center for sweat testing
* Sweat testing is still the “gold standard” for confirmation
* DNA testing for the most common CF mutations may be added to the screening protocol in the future

Newborn Screening Expansion-Biotinidase Deficiency
* Biotinidase deficiency is a recessive genetic disorder with a prevalence of 1:60,000 births (ethnic difference in prevalence not established)
* Like CF, risk of recurrence is 1:4 with each pregnancy
* Affected infants cannot utilize biotin, a vitamin found in foods, including breastmilk and infant formula
* Leads to developmental delay, seizures, hair loss, hearing loss, skin disorders and immunodeficiency
* Treated by giving infant biotin in the form of a crushed pill or capsule mixed into milk or food
* Screening will involve direct measurement of biotinidase
* False positive rates should be low

Newborn Screening Expansion-Fatty Acid, Amino Acid and Organic Acid Disorders
* Fatty acid, amino acid and organic acid disorders are individually rare, but occur with a combined frequency of 1:5000 to 1:6000 births
* Screening will include measurement of an acyl carnitine profile and an amino acid profile
* MS/MS is very precise, but interpretation is complex
* REMINDER--MS/MS can identify many, but not all metabolic disorders

Newborn Screening Expansion-Fatty Acid Disorders
* Most common FA disorder—MCADD—is part of the current test panel
* Expansion will add seven additional FA disorders
* All are recessive genetic disorders so risk of recurrence is 1:4 with each pregnancy
* Symptoms of most FA disorders
o Hypoketotic hypoglycemia
o Muscle weakness
o Seizures
o Sometimes cardiomyopathy
* Treatment of most FA disorders
o Avoid fasting
o Immediate medical attention when unable to eat usual diet
o Control type/amount of fat in diet depending upon the specific diagnosis
o Carnitine if indicated
o Cornstarch tube feeding at night if indicated
o Ensure immunizations are up-to-date
o Treat infections promptly
o All patients should keep an “emergency protocol” letter with them at all times
* Short chain acyl co-A dehydrogenase deficiency (SCADD)
o Estimated incidence is 1:40,000 to 1:100,000
o Outcomes of known patients highly variable, but may be less severe than other FA disorders
* Long chain 3 OH co-A dehydrogenase deficiency/Trifunctional protein defect (LCHADD/TFP)
o Unknown incidence
o Differential diagnosis needed to separate LCHADD from TFP
o Cardiomyopathy and retinal changes
o HELLP/AFLP in 20% of affected pregnancies
* Very long chain acyl co-A dehydrogenase deficiency (VLCADD)
o Unknown incidence
o Some infants have cardiomyopathy
o Good outcome when treated presymptomatically
* Glutaric aciduria type II (GA II)
o Not thought to be rare, but incidence unknown
o Outcomes variable based upon phenotype
o Riboflavin supplementation useful in some mild cases
* Carnitine Palmitoyltransferase II deficiency (CPT II)
o Unknown incidence
o Muscle weakness, pain and myoglobinuria prompted by prolonged exercise
o 80% affected patients have been male
o Cardiac dysfunction rare
* Carnitine/acylcarnitine translocase deficiency (CACT)
o Thought to be very rare
o Long term outcome not clearly known
* Expansion will add eleven OA disorders
* Most are recessive disorders so risk of recurrence is 1:4 with each pregnancy
* A few sub-types are X-linked so only males are affected, but females may show milder symptoms
* Symptoms of most OA disorders
o Feeding problems
o Seizures
o Metabolic acidosis
o Lethargy
* Treatment of most OA disorders
o Avoid fasting
o Immediate medical attention when unable to eat usual diet
o Control type/amount of protein in diet depending upon the specific diagnosis
o Carnitine if indicated
* Propionic acidemia (PA)
o Estimated incidence is 1:100,000
o Oral antibiotics may be useful to decrease gut propionate
o Biotin if helpful
o Continuous overnight feeds helpful in some patients
* Methylmalonic acidemia (MMA)
* Isobutyrul co-A dehydrogenase deficiency (IBCDD)
o Thought to be very rare
* Isovaleric acidemia (IVA)
* 2 methylbutyryl co-A dehydrogenase deficiency (2-MBCDD)
* 3 methylcrotonyl co-A carboxylase deficiency (3-MCC)
* Beta ketothiolase deficiency
* 3 methyl 3-OH glutaryl co-A lyase deficiency (HMGLD)
* 3 methylglutaconyl co-A hydratase deficiency

Newborn Screening Expansion-Organic Acid Disorders
* Multiple carboxylase deficiency (MCD)
o Estimated incidence is 1:87,000
o Diet restriction NOT indicated
o Most cases are biotin responsive
o Biotin enhances the function of the carboxylase enzymes
o Not the same as biotinidase deficiency!
* Glutaric aciduria type I (GA I)
o Estimated incidence is 1:40,000
o Very important to proceed directly to diagnostic testing with any elevation
o Must treat fever aggressively
o Hospital admission mandatory for IV’s with any vomiting illness
o Prone to subdural hemorrhages and retinal hemorrhages after minor head trauma (ie, fall when learning to walk)
o Can be misdiagnosed as child abuse
o May have profuse sweating


Newborn Screening Expansion-Amino Acid Disorders
* Most common AA disorder—PKU—is part of the current test panel
* Expansion will add four additional AA disorders
* All are recessive genetic disorders so risk of recurrence is 1:4 with each pregnancy
* Symptoms and treatments vary by disorder
* Homocystinuria
* Maple syrup urine disease (MSUD)
* Citrullinemia
* Argininosuccinic aciduria
Testing and Follow-up
Challenges in Ensuring Complete Follow-up

What’s New in Newborn Screening.ppt