1. Newborn Screening and Children’s Special Health Care Services
May 04, 2012
Newborn Screening and Children’s Special Health Care Services
Lois Turbett, MS, RN
Nurse Consultant

2. Purpose of Newborn Screening (NBS)
Early diagnosis
Early treatment
Reduce morbidity and mortality
Reduce financial burden

3. 50th Anniversary of NBS
Robert Guthrie publishes A Simple Phenylalanine Method for Detecting Phenylketonuria in Large Populations of Newborn Infants. Pediatrics 1963; 32:
1963 Massachusetts becomes the first state to mandate screening for phenylketonuria (PKU) in newborns

4. Early History of Michigan NBS
1965 PKU
1977 congenital hypothyroidism (CH)
1985 galactosemia
1987 biotinidase deficiency, maple sugar urine disease (MSUD) and hemoglobinopathies
1993 congenital adrenal hyperplasia (CAH)
additional metabolic disorders
2007 cystic fibrosis (CF)
2011 severe combined immunodeficiencies (SCID)

5. 217 Babies Diagnosed through NBS in 2011
Cystic fibrosis (13)
Endocrine (86)
Congenital hypothyroidism (78)
Congenital adrenal hyperplasia (8)
Hemoglobinopathies (61)
Metabolic disorders (57)
Primary immunodeficiencies (0)

6. Michigan Compiled Laws Section 333.5431
Mandated
Hospitals
Birthing attendants (midwives)
Parents may opt out
Rare
Fax signed refusal form to NBS Follow-up or

7. NBS Results
Faxed to the primary care provider (PCP) listed on the NBS card
Consult with medical management centers as needed
Explain to family meaning of screen
Arrange with family for a repeat newborn screen when requested
Make sure the family knows to give your contact information to the hospital

8. NBS Results on MCIR
NBS results are posted on Michigan Care Improvement Registry (MCIR)
Click on “Newborn Screening Tab”
Click on “Results” (opens PDF)
Primary care offices have access; local health departments (LHDs) usually do not

9. Now says “report”

10. Role of LHD CSHCS Know the disorders-more than a “PKU test”
Cystic fibrosis
Endocrine
Hemoglobinopathies
Metabolic
Primary immunodeficiencies
50+ disorders screened as well as hearing

11. NBS Results Normal Inconclusive and borderline
Fax report to management center
Fax report to primary care provider (PCP)
NBS Follow-up requests repeat screen

12. Role of LHD CSHCS, Borderline Positive (B+)
May 04, 2012
Role of LHD CSHCS, Borderline Positive (B+)
NBS referral sent to LHD via EZ Link
Check to see if family due in for WIC
Check to see if enrolled in Maternal Infant Health Program (MIHP)
Call family
Visit if in the neighborhood
Assist family to obtain a primary care provider (PCP) for infant
Obtain repeat screen at a local birthing hospital
LHD CSHCS is contacted if the family has not responded to certified letters sent from NBS follow-up, NBS is unable to reach family by phone, baby has not established care with a PCP. In other words, NBS has exhausted all resources. Then NBS contacts LHD.
Most B+ resolve as normal. Repeat screen needed, not CSHCS diagnostic referral.

14. NBS Results (cont.) Strong positive
Fax report to PCP
Fax report to management center; assure referral received
Management center assumes follow-up of strong positive referral

15. Role of LHD CSHCS, Strong Positive (S+)
CSHCS diagnostic referral
All NBS diagnoses are covered by CSHCS
Sub-specialist referral depends on the disorder

16. Medical Management Centers
Newborn Screening and Coordinating Program for Cystic Fibrosis (University of Michigan)
Newborn Screening Endocrine Follow-up Program (University of Michigan)
Sickle Cell Disease Association of America, Michigan Chapter
Children’s Hospital of Michigan Metabolic Clinic
Children’s Hospital of Michigan Coordinating Center for Primary Immunodeficiencies

17. Cystic Fibrosis (CF) High immunoreactive trypsinogen (IRT)
May 04, 2012
Cystic Fibrosis (CF)
High immunoreactive trypsinogen (IRT)
Enzyme created by the pancreas
High in infants with CF
Other conditions can also cause elevation
Mutation for Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)
Michigan tests for 40 common mutations
This is what NBS is looking for. I can delete this slide if this PP is too long.

18. Cystic Fibrosis (CF) (cont.)
May 04, 2012
Cystic Fibrosis (CF) (cont.)
High IRT, no mutation
Primary care provider (PCP) notified
PCP to monitor health status of infant
High IRT, one or two mutations
Referral to management center
Arrange for sweat chloride test
Notify NBS follow-up if the mother of a CSHCS CF client is pregnant
1.7% of strong positive referrals for one mutation were confirmed to have cystic fibrosis in It is sometimes difficult to get parents to take the infant for confirmatory testing (sweat test) when only one mutation is identified, since it is very likely the infant is just a carrier. However, there are over 2000 mutation known to cause CF and Michigan tests for 40.

19. May 04, 2012
Role of LHD CSHCS, S+ CF
CSHCS diagnostic referral to a certified CF center for sweat test
Helen DeVos Children’s Hospital
Western Michigan University, Kalamazoo
Michigan State University, Lansing
Mott (Ann Arbor & Flint)
Children’s Hospital of Michigan
Toledo (borderland)
I need to work on this slide. The UP is a problem since I think CSHCS won’t authorized OOS diagnostic referrals for CF. Do you know otherwise?

20. Congenital Hypothyroidism (CH)
Test for thyroid stimulating hormone (TSH)
Cutoffs vary depending on age
Untreated CH may lead to irreversible decreased intellectual ability

21. Role of LHD CSHCS S+ CH
Medical management center refers to pediatric endocrinologist for serum TSH and serum free T4
CSHCS diagnostic referral if indicated
Insurance prior authorization for Synthroid instead of levothyroxine

22. Congenital Adrenal Hyperplasia (CAH)
17-hydroxyprogesterone (17-OPH)
Newborn may already show signs of CAH while in the hospital
Ambiguous genitalia (female)
Clinical picture

23. Role of LHD CSHCS S+ CAH
Immediate referral to pediatric endocrinologist
CSHCS diagnostic referral
Retroactive diagnostic
CSHCS backdating
CSHCS nurse should assure family understanding of written emergency plan for CAH

24. Hemoglobinopathies Sickle cell anemia β thalassemia
May 04, 2012
Hemoglobinopathies
Sickle cell anemia
β thalassemia
Sickle β thalassemia
Hb H disease ( thalassemia)
Hemoglobin H Disease
Michigan began screening for Hemoglobin H disease, one of the alpha thalassemia disorders, in To date, seven cases have been diagnosed. The predominant hemoglobin in newborns is fetal hemoglobin (HbF), which is comprised of a tetramer formed by two alpha and two gamma chains. HbF is gradually replaced by adult hemoglobin (HbA) as the baby gets older. HbA is comprised of a tetramer formed by two alpha and two beta chains. There are four genes that regulate the production of alpha chains and two genes that regulate the production of gamma and beta chains. One, two or three alpha gene deletions or mutations cause fewer alpha chains to be produced. When this happens, there are more HbF gamma chains than there are HbF alpha chains. The excess gamma chains form a tetramer called hemogoblin Bart’s, which is detected through newborn screening. As more HbA is produced, an excess of beta chains is created. The excess beta chains form a tetramer called hemoglobin H.
The presence of hemoglobin Bart’s indicates that one or more of the four genes that produce alpha globin chains are dysfunctional, causing alpha thalassemia. Low levels of Bart’s is often clinically insignificant. High levels of Bart’s most often indicates that three of the alpha genes are dysfunctional. The clinical manifestations of this disorder are variable but most patients have chronic hemolysis, moderate anemia and develop some degree of splenomegaly. Patients may require transfusions and iron chelation therapy.
Hemoglobin H Disease with Hemoglobin Constant Spring
Hemoglobin H disease with hemoglobin Constant Spring is typically more severe than the more common form of Hemoglobin H disease. This occurs when there are two alpha gene deletions and a third Constant Spring mutation. The clinical manifestations of this disorder include moderate anemia, splenomegaly, and possible transfusion dependence.

25. Role of LHD CSHCS Hemoglobinopathies
May 04, 2012
Role of LHD CSHCS Hemoglobinopathies
CSHCS diagnostic referral
Be familiar with pain management challenges
Ask to see the patient’s notebook
Transition to adult Hem/Onc
Consult with the SCDAA, Michigan Chapter if you do not understand the significance of the NBS report

26. Metabolic Disorders Amino acid disorders Fatty acid disorders
May 04, 2012
Metabolic Disorders
Amino acid disorders
Fatty acid disorders
Organic acid disorders
Other disorders
I will go through the metabolic slides quickly

27. Amino Acid Disorders Phenylketonuria (PKU)
May 04, 2012
Amino Acid Disorders
Phenylketonuria (PKU)
Classic PKU
Non-PKU hyperphenylalanemia
Maple sugar urine disease (MSUD)
Arginosuccinic acidemia (ASA)
Citrullinemia type I (CIT-I)
Arginase deficiency (ARG)
Citrullinemia type II (CIT-II)
Amish-PKU, MSUD, glutaric acidemia type I.

28. Fatty Acid Disorders Carnitine uptake defect (CUD)
May 04, 2012
Fatty Acid Disorders
Carnitine uptake defect (CUD)
Medium-chain acyl-CoA dehydrogenase deficiency (MCAD)
Very long-chain acyl-CoA dehydrogenase deficiency (VLCAD)
Avoid fasting. Low fat, high carbs q2-6 hrs.

29. Organic Acid Disorders
May 04, 2012
Organic Acid Disorders
2MBG - 2-Methylbutyryrl-CoA dehydrogenase deficiency
Isovaleric acidemia (IVA)
Glutaric acidemia Type I
Amish-GA-I
maple syrup urine disease has both elevated amino acids and elevated organic acids derived from these amino acids.

30. Other Disorders Classic galactosemia Duarte galactosemia
Life threatening
Immediate switch to soy formula; discontinue breastfeeding
Duarte galactosemia
Mild, often no treatment
Biotinidase deficiency
Treated with daily biotin

31. Role of LHD CSHCS Metabolic Disorders
May 04, 2012
Role of LHD CSHCS Metabolic Disorders
Know the disorder for your enrolled child
Many disorders can be life threatening; others are mild
Assure family understanding of written emergency plan
Access to care issues
Detroit, Grand Rapids, Ann Arbor
Amarillo TX to Brownsville TX 12.5 hrs
El Paso TX to Houston TX hrs
Ironwood MI to Detroit MI 10.5 hrs
Ironwood to Ann Arbor 10+ hrs through MI; close to 12 hrs through WI
Ironwood to Duluth 2.25 hrs
Marquette to Detroit 8 hrs
Marquette to Ann Arbor 7.5 hrs
Marquette to Grand Rapids 7 hrs
Marquette to Milwaukee, WI 5.5 hrs
Marquette to Green Bay, WI 3.5 hrs

32. Role of LHD CSHCS Metabolic Disorders
Prior authorization challenges for metabolic formula
Lifetime PKU diet
Maternal PKU
May need to get mom back on CSHCS if pregnant and <21
Baby can develop permanent intellectual impairment if mother does not follow diet

33. Severe Combined Immunodeficiency (SCID)
A group of inherited disorders characterized by the lack of a functioning immune system
“Combined” defect in both T and B-cell function
Exposure to common illnesses and live vaccines is life threatening
I will go through this quickly also

34. NBS SCID Testing Test for T-cell receptor excision circles (TRECs)
By-product generated during T-cell development
Low or absent number means infant is not making T-cells
Michigan began testing for SCID October 3, 2011

35. Role of LHD CSHCS Primary Immunodeficiencies
May 04, 2012
Role of LHD CSHCS Primary Immunodeficiencies
Diagnostic referral, flow cytometry
DeVos
University of Michigan
Children’s Hospital of Michigan
If true SCID, bone marrow transplant (BMT) is likely
May need intravenous immune globulin (IVIG) until BMT
This is a specialized flow cytometry that can only be done at these three centers. If the baby is not near DeVos or Mott, the SCID nurse from CHM will arrange for a local blood draw and have the blood sent to CHM.

36. Recap B+, repeat newborn screen needed S+, CSHCS diagnostic referral
Confirmed case, CSHCS eligible

37. NBS Newsletter Online

38. Covered by CSHCS

39. May 04, 2012

40. NBS Information 866-673-9939 Fax 517-335-9419
May 04, 2012
NBS Information
Fax
Lois Turbett