Whats New in Newborn Screening

Kathy Tomashitis, MNS, RD Pediatric Screening Coordinator Division of Women and Childrens Services, SC DHEC

Newborn Screening Expansion

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

Newborn Screening-Why Expand the Test Panel

Several factors have lead to the current expansion

Technological advances: increased use of tandem mass spectrometry (MS/MS) in newborn screening applications and improvement in the screening protocol for cystic fibrosis NO ADDITIONAL BLOOD NEEDED!

Newborn Screening-Why Expand the Test Panel

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 Cost benefit: research supports pre-symptomatic identification of fatty acid, amino acid and organic acid disorders found through MS/MS

Newborn Screening-Why Expand the Test Panel

SC health care providers support expanded screening

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 Newborn Screening Advisory Committee recommended step-wise expansion to include cystic fibrosis, biotinidase deficiency and disorders found through MS/MS

Newborn Screening-Why Expand the Test Panel

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 ExpansionCystic 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.

Newborn Screening ExpansionCystic Fibrosis

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

Newborn Screening ExpansionCystic Fibrosis

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

Newborn Screening ExpansionCystic Fibrosis

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 ExpansionBiotinidase 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

Newborn Screening ExpansionBiotinidase Deficiency

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 ExpansionFatty 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

Newborn Screening ExpansionFatty Acid, Amino Acid and Organic Acid Disorders
MS/MS is very precise, but interpretation is complex REMINDER--MS/MS can identify many, but not all metabolic disorders

Newborn Screening ExpansionFatty Acid Disorders

Most common FA disorderMCADDis 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

Newborn Screening ExpansionFatty Acid Disorders

Symptoms of most FA disorders

Hypoketotic hypoglycemia Muscle weakness Seizures Sometimes cardiomyopathy

Newborn Screening ExpansionFatty Acid Disorders

Treatment of most FA disorders

Avoid fasting Immediate medical attention when unable to eat usual diet Control type/amount of fat in diet depending upon the specific diagnosis Carnitine if indicated Cornstarch tube feeding at night if indicated

Newborn Screening ExpansionFatty Acid Disorders

Treatment (cont)

Ensure immunizations are up-to-date Treat infections promptly All patients should keep an emergency protocol letter with them at all times

Newborn Screening ExpansionFatty Acid Disorders

MINOR ILLNESSES CAN PRECIPITATE METABOLIC DECOMPENSATION IN AN INFANT/CHILD WITH A FA DISORDER!!

Newborn Screening ExpansionFatty Acid Disorders

Short chain acyl co-A dehydrogenase deficiency (SCADD)

Estimated incidence is 1:40,000 to 1:100,000 Outcomes of known patients highly variable, but may be less severe than other FA disorders

Newborn Screening ExpansionFatty Acid Disorders

Long chain 3 OH co-A dehydrogenase deficiency/Trifunctional protein defect (LCHADD/TFP)

Unknown incidence Differential diagnosis needed to separate LCHADD from TFP Cardiomyopathy and retinal changes HELLP/AFLP in 20% of affected pregnancies

Newborn Screening ExpansionFatty Acid Disorders

Very long chain acyl co-A dehydrogenase deficiency (VLCADD)

Unknown incidence Some infants have cardiomyopathy Good outcome when treated presymptomatically

Newborn Screening ExpansionFatty Acid Disorders

Glutaric aciduria type II (GA II)

Not thought to be rare, but incidence unknown Outcomes variable based upon phenotype Riboflavin supplementation useful in some mild cases

Newborn Screening ExpansionFatty Acid Disorders

Carnitine Palmitoyltransferase II deficiency (CPT II)

Unknown incidence Muscle weakness, pain and myoglobinuria prompted by prolonged exercise 80% affected patients have been male Cardiac dysfunction rare

Newborn Screening ExpansionFatty Acid Disorders

Carnitine/acylcarnitine translocase deficiency (CACT)

Thought to be very rare Long term outcome not clearly known

Newborn Screening ExpansionOrganic Acid Disorders

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

Newborn Screening ExpansionOrganic Acid Disorders

Symptoms of most OA disorders

Feeding problems Seizures Metabolic acidosis Lethargy

Newborn Screening ExpansionOrganic Acid Disorders

Treatment of most OA disorders

Avoid fasting Immediate medical attention when unable to eat usual diet Control type/amount of protein in diet depending upon the specific diagnosis Carnitine if indicated

Newborn Screening ExpansionOrganic Acid Disorders

Treatment (cont)

Ensure immunizations are up-to-date Treat infections promptly All patients should keep an emergency protocol letter with them at all times

Newborn Screening ExpansionOrganic Acid Disorders

MINOR ILLNESSES CAN PRECIPITATE METABOLIC DECOMPENSATION IN AN INFANT/CHILD WITH AN OA DISORDER!!

Newborn Screening ExpansionOrganic Acid Disorders

Propionic acidemia (PA)

Estimated incidence is 1:100,000 Oral antibiotics may be useful to decrease gut propionate Biotin if helpful Continuous overnight feeds helpful in some patients

Newborn Screening ExpansionOrganic Acid Disorders

Methylmalonic acidemia (MMA)

Estimated incidence is 1:48,000 for B-12 nonresponsive type; unknown incidence in other types Oral antibiotics may be useful to decrease gut propionate Vitamin B-12 if helpful Betaine if helpful

Newborn Screening ExpansionOrganic Acid Disorders

Isobutyrul co-A dehydrogenase deficiency (IBCDD)

Thought to be very rare Long term outcome not clearly known, but appears to be good

Newborn Screening ExpansionOrganic Acid Disorders

Isovaleric acidemia (IVA)

Estimated incidence is 1:230,000 Most have sweaty sock odor Glycine may be used in addition to carnitine

Newborn Screening ExpansionOrganic Acid Disorders

2 methylbutyryl co-A dehydrogenase deficiency (2-MBCDD)

Thought to be very rare Long term outcome not clearly known, but appears to be good

Newborn Screening ExpansionOrganic Acid Disorders

3 methylcrotonyl co-A carboxylase deficiency (3-MCC)

Estimated incidence is 1:50,000 Glycine may be used in addition to carnitine NBS result in infant may really be indicative of maternal 3-MCC

Newborn Screening ExpansionOrganic Acid Disorders

Beta ketothiolase deficiency

Unknown incidence Urinary ketones should be monitored Moderate protein intake indicated Bicarbonate therapy often required long term

Newborn Screening ExpansionOrganic Acid Disorders

3 methyl 3-OH glutaryl co-A lyase deficiency (HMGLD)

Unknown incidence Diet may also be somewhat restricted in fat Supplemental glucose may be used

Newborn Screening ExpansionOrganic Acid Disorders

3 methylglutaconyl co-A hydratase deficiency

Thought to be very rare Type II is X-linked Protein restriction and supplemental carnitine may be useful for Type I Other types do not appear to respond to treatment

Newborn Screening ExpansionOrganic Acid Disorders

Multiple carboxylase deficiency (MCD)

Estimated incidence is 1:87,000 Diet restriction NOT indicated Most cases are biotin responsive Biotin enhances the function of the carboxylase enzymes Not the same as biotinidase deficiency!

Newborn Screening ExpansionOrganic Acid Disorders

Glutaric aciduria type I (GA I)

Estimated incidence is 1:40,000 Very important to proceed directly to diagnostic testing with any elevation Must treat fever aggressively Hospital admission mandatory for IVs with any vomiting illness

Newborn Screening ExpansionOrganic Acid Disorders

Glutaric aciduria type I (GA I) cont

Prone to subdural hemorrhages and retinal hemorrhages after minor head trauma (ie, fall when learning to walk) Can be misdiagnosed as child abuse May have profuse sweating

Newborn Screening ExpansionAmino Acid Disorders

Most common AA disorderPKUis 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

Newborn Screening ExpansionAmino Acid Disorders

Homocystinuria

Estimated incidence is 1:200,000 Dislocated lens, marfanoid body type, thromboembolism Some patients are vitamin B 6 responsive MET restricted diet if B 6 non-responsive Betaine used after infancy Monitor folate/B 12 and supplement if needed

Newborn Screening ExpansionAmino Acid Disorders

Maple syrup urine disease (MSUD)

Estimated incidence is 1:185,000 Severe ketoacidosis, ammonia, sezuires, coma LEU restricted/ILE, VAL controlled diet Thiamin if responsive

Newborn Screening ExpansionAmino Acid Disorders

Citrullinemia

Estimated incidence is 1:57,000 ammonia, lethargy, seizures, coma Protein restricted diet, ARG supplementation Na benzoate, Na phenylacetate, Na phenylbutyrate if indicated Aggressive treatment when ammonia levels

Newborn Screening ExpansionAmino Acid Disorders

Argininosuccinic aciduria

Estimated incidence is 1:70,000 ammonia, lethargy, seizures, coma Protein restriction, ARG supplementation Na benzoate, Na phenylacetate, Na phenylbutyrate if indicated Aggressive treatment when ammonia levels

Testing and Follow-up

State law requires all infants to be tested before hospital discharge regardless of their length of stay. DHEC laboratory performs all newborn screening tests. All results (normal, unacceptable and abnormal) are sent to the physician of record and the hospital or birthing center. Repeat tests are required when: one of the screening tests was abnormal, the initial sample was unacceptable, the initial sample was collected before 24 hours of age.

Testing and Follow-up

Follow-up program calls physician of record when results are highly suggestive of a case. Follow-up program sends letter to physician of record to document phone call.

Testing and Follow-up

Follow-up program sends letter to physician of record when results are outside of normal limits, but not highly suggestive of a case.

Testing and Follow-up

By allowing name to be put on collection form, physician assumes all responsibility for ensuring repeat specimens are collected.

Testing and Follow-up

If physician of record not providing care after hospital stay, he/she must notify DHEC as soon as possible so that local health department staff can ensure repeat specimens are collected.

Challenges in Ensuring Complete Follow-up

Name changes Incomplete demographic data Marking lab slip wrong (i.e. mark PKU when needed T4) Incorrect coding of MD or record

Newborn Screening Expansion

FINAL WORDSNever call newborn screening the PKU test!! Contact information general info: Kathy Tomashitis phone: 803-898-0619 email: tomashkf@dhec.sc.gov

Newborn Screening Expansion

Contact information (cont) Patient results: Linda Baker phone: 803-898-0593 fax: 803-898-0337 Medical consultant: Dr Bryant Fortner phone: 803-898-0362 email: fortnebr@dhec.sc.gov