Whats New in Newborn Screening

1
Whats New in Newborn Screening

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

2
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 pre-symptomatic
  detection for specific disorders

3
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!

4
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

5
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

6
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

7
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

8
Newborn Screening Expansion-Cystic Fibrosis

• Cystic fibrosis is a genetic disorder that is
  found in 13500 Caucasian and 117,000 African
  American births
• CF is a recessive genetic disorder. Risk of
  recurrence is 14 with each pregnancy.
• In CF, the pulmonary and gastrointestinal systems
  are severely compromised.

9
Newborn Screening Expansion-Cystic 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

10
Newborn Screening Expansion-Cystic 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

11
Newborn Screening Expansion-Cystic 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

12
Newborn Screening Expansion-Biotinidase Deficiency

• Biotinidase deficiency is a recessive genetic
  disorder with a prevalence of 160,000 births
  (ethnic difference in prevalence not established)
• Like CF, risk of recurrence is 14 with each
  pregnancy
• Affected infants cannot utilize biotin, a vitamin
  found in foods, including breastmilk and infant
  formula

13
Newborn Screening Expansion-Biotinidase 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

14
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 15000 to 16000 births
• Screening will include measurement of an acyl
  carnitine profile and an amino acid profile

15
Newborn Screening Expansion-Fatty 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

16
Newborn Screening Expansion-Fatty 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 14 with each pregnancy

17
Newborn Screening Expansion-Fatty Acid Disorders

• Symptoms of most FA disorders
• Hypoketotic hypoglycemia
• Muscle weakness
• Seizures
• Sometimes cardiomyopathy

18
Newborn Screening Expansion-Fatty 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

19
Newborn Screening Expansion-Fatty 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

20
Newborn Screening Expansion-Fatty Acid Disorders

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

21
Newborn Screening Expansion-Fatty Acid Disorders

• Short chain acyl co-A dehydrogenase deficiency
  (SCADD)
• Estimated incidence is 140,000 to 1100,000
• Outcomes of known patients highly variable, but
  may be less severe than other FA disorders

22
Newborn Screening Expansion-Fatty 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

23
Newborn Screening Expansion-Fatty Acid Disorders

• Very long chain acyl co-A dehydrogenase
  deficiency (VLCADD)
• Unknown incidence
• Some infants have cardiomyopathy
• Good outcome when treated presymptomatically

24
Newborn Screening Expansion-Fatty 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

25
Newborn Screening Expansion-Fatty 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

26
Newborn Screening Expansion-Fatty Acid Disorders

• Carnitine/acylcarnitine translocase deficiency
  (CACT)
• Thought to be very rare
• Long term outcome not clearly known

27
Newborn Screening Expansion-Organic Acid Disorders

• Expansion will add eleven OA disorders
• Most are recessive disorders so risk of
  recurrence is 14 with each pregnancy
• A few sub-types are X-linked so only males are
  affected, but females may show milder symptoms

28
Newborn Screening Expansion-Organic Acid Disorders

• Symptoms of most OA disorders
• Feeding problems
• Seizures
• Metabolic acidosis
• Lethargy

29
Newborn Screening Expansion-Organic 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

30
Newborn Screening Expansion-Organic 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

31
Newborn Screening Expansion-Organic Acid Disorders

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

32
Newborn Screening Expansion-Organic Acid Disorders

• Propionic acidemia (PA)
• Estimated incidence is 1100,000
• Oral antibiotics may be useful to decrease gut
  propionate
• Biotin if helpful
• Continuous overnight feeds helpful in some
  patients

33
Newborn Screening Expansion-Organic Acid Disorders

• Methylmalonic acidemia (MMA)
• Estimated incidence is 148,000 for B-12
  non-responsive type unknown incidence in other
  types
• Oral antibiotics may be useful to decrease gut
  propionate
• Vitamin B-12 if helpful
• Betaine if helpful

34
Newborn Screening Expansion-Organic Acid Disorders

• Isobutyrul co-A dehydrogenase deficiency (IBCDD)
• Thought to be very rare
• Long term outcome not clearly known, but appears
  to be good

35
Newborn Screening Expansion-Organic Acid Disorders

• Isovaleric acidemia (IVA)
• Estimated incidence is 1230,000
• Most have sweaty sock odor
• Glycine may be used in addition to carnitine

36
Newborn Screening Expansion-Organic 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

37
Newborn Screening Expansion-Organic Acid Disorders

• 3 methylcrotonyl co-A carboxylase deficiency
  (3-MCC)
• Estimated incidence is 150,000
• Glycine may be used in addition to carnitine
• NBS result in infant may really be indicative of
  maternal 3-MCC

38
Newborn Screening Expansion-Organic Acid Disorders

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

39
Newborn Screening Expansion-Organic 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

40
Newborn Screening Expansion-Organic 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

41
Newborn Screening Expansion-Organic Acid Disorders

• Multiple carboxylase deficiency (MCD)
• Estimated incidence is 187,000
• Diet restriction NOT indicated
• Most cases are biotin responsive
• Biotin enhances the function of the carboxylase
  enzymes
• Not the same as biotinidase deficiency!

42
Newborn Screening Expansion-Organic Acid Disorders

• Glutaric aciduria type I (GA I)
• Estimated incidence is 140,000
• Very important to proceed directly to diagnostic
  testing with any elevation
• Must treat fever aggressively
• Hospital admission mandatory for IVs with any
  vomiting illness

43
Newborn Screening Expansion-Organic 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

44
Newborn Screening Expansion-Amino 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 14 with each pregnancy
• Symptoms and treatments vary by disorder

45
Newborn Screening Expansion-Amino Acid Disorders

• Homocystinuria
• Estimated incidence is 1200,000
• 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

46
Newborn Screening Expansion-Amino Acid Disorders

• Maple syrup urine disease (MSUD)
• Estimated incidence is 1185,000
• Severe ketoacidosis, ? ammonia, sezuires, coma
• LEU restricted/ILE, VAL controlled diet
• Thiamin if responsive

47
Newborn Screening Expansion-Amino Acid Disorders

• Citrullinemia
• Estimated incidence is 157,000
• ? ammonia, lethargy, seizures, coma
• Protein restricted diet, ARG supplementation
• Na benzoate, Na phenylacetate, Na phenylbutyrate
  if indicated
• Aggressive treatment when ammonia levels ?

48
Newborn Screening Expansion-Amino Acid Disorders

• Argininosuccinic aciduria
• Estimated incidence is 170,000
• ? ammonia, lethargy, seizures, coma
• Protein restriction, ARG supplementation
• Na benzoate, Na phenylacetate, Na phenylbutyrate
  if indicated
• Aggressive treatment when ammonia levels ?

49
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.

50
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.

51
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.

52
Testing and Follow-up

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

53
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.

54
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

55
Newborn Screening Expansion

• FINAL WORDSNever call newborn screening the PKU
  test!!
• Contact information
• general info Kathy Tomashitis
• phone [phone]
• email tomashkf_at_dhec.sc.gov

56
Newborn Screening Expansion

• Contact information (cont)
• Patient results Linda Baker
• phone [phone]
• fax [phone]
• Medical consultant Dr Bryant Fortner
• phone [phone]
• email fortnebr_at_dhec.sc.gov