Expanded Newborn Screening: The Nutrition Perspective

Expanded Newborn Screening: The Nutrition Perspective
By:Beth Ogata, MS, RD

Nutrition Involvement in NBS
* Policy
* Diagnostic/coordination
* Clinical
* Community
Example: infant with galactosemia
* Symptoms in newborn, if untreated
o Vomiting, diarrhea
o Hyperbilirubinemia, hepatic dysfunction, hepatomegaly
o Renal tubular dysfunction
o Cataracts
o Encephalopathy
o E. coli septicemia result
o Death within 6 weeks, if untreated
o Duarte variant
o galactokinase deficiency
o uridine diphosphate-galactose-4-epimerase deficiency
Galactose-1-phosphate uridyl transferase (GALT) deficiency
Example: infant with galactosemia
* Primary source is milk (lactose= galactose + glucose)
* Secondary sources are legumes
* Minor? sources are fruits and vegetables
* Food labels
o milk, casein, milk solids, lactose, whey, hydrolyzed protein, lactalbumin, lactostearin, caseinate
* Medications (lactose is often an inactive ingredient)
* Dietary supplements
* Artificial sweeteners
Monitoring: galactose-1-phosphate levels <3-4 mg/dl
Treatment: eliminate all galactose from diet

Example: Infant with galactosemia
DIAGNOSIS & COOORDINATION
CLINICAL MANAGEMENT
RD as case manager
Nutrition and NBS: Policy
Nutrition and NBS: Clinical Management – PKU
* Phenylketonuria
o Phenylalanine hydroxylase
o Dihydropteridine reductase
o Biopterin synthetase
* Establish diagnosis
o Presumptive positive NBS results
+ > 3 mg/dL, >24 hrs of age
o Differential diagnosis
+ serum phe, nl tyr
+ r/o DHPR, biopterin defects

Current Treatment Guidelines
* With effective NBS, children are identified by 7 days of age
* Initiate treatment immediately
* Maintain phe levels 1-6 mg/dl (60-360 umol/L)
* Lifelong treatment
Outcome Expectations
Clinical Management: PKU
Goals of Nutrition Therapy
* Normal growth rate
* Normal physical development
* Normal cognitive development
* Normal nutritional status
* Correct substrate imbalance
* Supply product of reaction
o Supplement tyrosine to
Goals of Nutrition Support for Phenylketonuria (PKU)
Interpretation of phenylalanine levels
Adjustments necessary to maintain “safe” blood phe levels
Management Tools
Formula Composition
* Regulated by FDA
o Renal solute load
o Carbohydrate source
o Fat source
o Amino acid source
o Vitamin and mineral content
* Designated by clinician
o Protein/energy ratio
o Specific amino acid
o Fluid balance
o Total protein
o Total energy
Effect of a single amino acid deficiency on growth
Food Choices for PKU
Tools of Management: Low protein food products
Typical Food Pattern for a Child with PKU
Monitoring Adequacy of Treatment
Effective Blood Level Management in Childhood
Self-management Skills
Goal of Lifetime Management of PKU
Maternal PKU Concerns/Outcomes
Nutrition and NBS: Community – Glutaric Acidemia, type I
Glutaryl-CoA dehydrogenase deficiency
Example: Infant with GAI
Nutrition and NBS: Community
The baby has a “positive PKU test
Critical Questions about Follow-up and Coordination of Treatment
What you need to know
Caveats to Ponder

Expanded Newborn Screening: The Nutrition Perspective.ppt

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Quick Reference to Newborn Screening Disorders

Quick Reference to Newborn Screening Disorders

Biotinidase Deficiency - BIOT is an enzyme deficiency that occurs in about 1 in 60,000 U.S. newborns and can result in seizures, hearing loss, and death in severe cases. Treatment is simple and involves daily doses of biotin.

Congenital Adrenal Hyperplasia – 21-Hydroxylase Deficiency - CAH is caused by decreased or absent production of certain adrenal hormones. The most prevalent type is detected by newborn screening in about 1 in 9,000 Texas newborns. Early detection can prevent death in boys and girls and sex misassignment in girls. Treatment involves lifelong hormone replacement therapy.

Congenital Hypothyroidism Inadequate or absent production of thyroid hormone results in CH and is present in about 1 in 2,000 Texas newborns. Thyroid hormone replacement therapy begun by 1 month of age can prevent mental and growth retardation.

Galactosemia – Galactose-1-Phosphate Uridyltransferase (GALT) Deficiency - Failure to metabolize the milk sugar galactose results in GAL and occurs in about 1 in 50,000 U.S. newborns. The classical form detected by newborn screening can lead to cataracts, liver cirrhosis, mental retardation and/or death. Treatment is elimination of galactose from the diet usually by substituting soy for milk products.

Homocystinuria - HCY is caused by an enzyme deficiency that blocks the metabolism of an amino acid that can lead to mental retardation, osteoporosis and other problems if left undetected and untreated. The incidence is approximately 1 in 350,000 U.S. newborns. Treatment may involve a restricted protein diet and supplemental medicines, including Vitamin B6.

Maple Syrup Urine Disease (MSUD) - MSUD is a defect in the way that the body metabolizes certain amino acids and is present in about 1 in 200,000 U.S. newborns. Early detection and treatment with a restricted protein diet can prevent death and severe mental retardation. There is an increased risk in Mennonites.

Medium Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency - The most common disorder in the way the body metabolizes fatty acids is called MCAD deficiency. Undetected, it can cause sudden death. Treatment is simple and includes ensuring frequent food intake. The incidence from newborn screening is not yet known, but is thought to be approximately 1 in 15,000 U.S. newborns.

Phenylketonuria (PKU) - An enzyme defect that prevents metabolism of phenylalanine, an amino acid essential to brain development, is known as PKU and occurs in approximately 1 in every 23,000 Texas newborns. Undetected and untreated with a special restricted protein diet, PKU leads to irreversible mental retardation.

Sickle Cell Disease (SCD) – includes Sickle Cell Anemia (Hb SS), Sickle Beta Thalassemia (Hb S/?Th) and Sickle-Hemoglobin C Disease (Hb S/C) - Sickle cell anemia is the most prevalent SCD and causes clogged blood vessels resulting in severe pain and other severe health problems. Newborn screening detects about 1 in 2,500 Texas newborns with SCD annually. Persons of African or Mediterranean descent are at an increased risk. Early treatment with daily penicillin prevents death in the first few years of life.

Tyrosinemia Type I -TYR is caused by a deficiency in the liver of one enzyme that breaks down tyrosine. If not treated, the condition causes severe liver disease and other health problems. Treatment consists of medication including vitamin D and nitisinone, and a special restricted protein diet. Estimated incidence is 1 case in every 100,000 live births.

Fatty Acid Oxidation (FAO) Disorders include Carnitine Uptake Defect (CUD), Long-Chain Hydroxyacyl-CoA Dehydrogenase Deficiency (LCHAD), Trifunctional Protein Deficiency (TFP) and Very-Long-Chain Acyl-Co A Dehydrogenase Deficiency (VLCAD) - Disorders besides MCAD deficiency, other FAO disorders may be detected through newborn screening. They are usually described in categories based on the length of the fatty acid involved. Undetected and untreated they can cause seizures, coma, and even death. Treatment may include a low fat diet, frequent food intake, supplementation with L-Carnitine (Carnitor) and medium chain triglycerides.

Organic Acid (OA) Disorders include 3-Methylcrotonyl-CoA Carboxylase Deficiency (3MCC), Beta-Ketothiolase Deficiency (BKD), Glutaric Acidemia Type I (GAI), Hydroxymethylglutaric Aciduria (HMG), Isovaleric Acidemia (IVA) Methylmalonic Acidemia(MMA) (Cbl A and Cbl B forms) ( Cbl A,B), Methylmalonic Acidemia (mutase deficiency form) (MUT), Multiple Carboxylase Deficiency (MCD) and Propionic Acidemia (PROP) - Organic acidemias are a group of metabolic disorders that lead to accumulation of organic acids in the blood and urine and may be detected in newborn screening through analysis of acylcarnitine profiles. Symptoms can be diminished by restricting protein in the diet and supplementation with vitamins and/or L-Carnitine.

Urea Cycle Disorders (UCD) include Argininosuccinic Acidemia (ASA) and Citrullinemia (CIT) - A UCD is a genetic disorder caused by a deficiency of one of the enzymes responsible for removing ammonia from the blood stream. Some UCDs may be detected as a part of newborn screening. They are characterized by seizures, poor muscle tone, respiratory distress, and coma, and result in death if left undetected and untreated. Treatment is by a special restricted protein diet and medications including phenylbutyrate to remove ammonia.

Quick Reference to Newborn Screening Disorders.ppt

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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

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