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

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

50th Anniversary of NBS Robert Guthrie publishes A Simple Phenylalanine Method for Detecting Phenylketonuria in Large Populations of Newborn Infants. Pediatrics 1963; 32:338-342 1963 Massachusetts becomes the first state to mandate screening for phenylketonuria (PKU) in newborns

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) 2003-2005 additional metabolic disorders 2007 cystic fibrosis (CF) 2011 severe combined immunodeficiencies (SCID)

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)

Michigan Compiled Laws Section 333.5431 Mandated Hospitals Birthing attendants (midwives) Parents may opt out Rare Fax signed refusal form to NBS Follow-up 517-335-9419 or 517-335-9739

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

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

Now says “report”

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

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

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.

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

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

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

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.

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 2011 . 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.

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?

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

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

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

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

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 2011. 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.

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 800-842-0973

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

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.

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.

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.

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

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 10.5-11 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

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

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

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

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.

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

NBS Newsletter Online www.michigan.gov/newbornscreening

Covered by CSHCS

May 04, 2012

NBS Information 866-673-9939 Fax 517-335-9419 May 04, 2012 NBS Information 866-673-9939 Fax 517-335-9419 newbornscreening@michigan.gov www.michigan.gov/newbornscreening www.michigan.gov/biotrust Lois Turbett turbettl@michigan.gov 517-335-1966