CT Children's CLASP Guideline

Home , Argininemia, Duarte galactosemia, Tyrosinemia type II, Tyrosinemia type III

CT Children’s CLASP Guideline

The Role of Primary Care in the Evaluation & Management of Out-of-Range Newborn Screens: Collaboration with the CT Newborn Diagnosis & Treatment Network

INTRODUCTION Newborn screening (NBS) is the well-established practice of testing all babies in their first days of life for certain disorders and conditions that can hinder normal growth and development. This testing is required in every state and is usually done before the baby leaves the hospital. The conditions screened for with NBS can cause serious health problems that start in infancy or childhood. Since these infants can appear healthy at birth, early detection with newborn screening allows doctors, and their care teams, to start treatment and to prevent morbidity and mortality.

When a baby is 24-48 hours old, blood taken by heel stick is sent to the Connecticut Department of Public Health (DPH) at the State Laboratory for screening. Screening tests are currently available for more than 60 disorders in CT. The CT newborn screening panel is based on the recommendations of the US Department of Health and Human Services Advisory Committee on Heritable Disorders in Newborns and Children. With advances in NBS over the coming years, we expect more conditions to be added to the Recommended Uniform Screening Panel (RUSP). See Appendix #1 for a list of current disorders screened for in Connecticut.

The Connecticut Newborn Diagnosis and Treatment Network, or “the Network,” was formed in 2019. Funded through the CT DPH, and based at Connecticut Children’s Medical Center, the Network responds to all reports of infants who have a NBS that flags out of range. In coordination with the infant’s primary care provider (PCP) or hospital based medical provider (HBMP), the Network will begin the diagnostic work-up, and provide support to the healthcare team and family as needed. If an infant confirms positive for a disorder, the Network will coordinate treatment and long-term follow-up for the condition identified, working with PCPs, hospitals and specialists statewide.

Genetic Counseling Services All families of newborns with an out of range newborn screen have the option to speak to a genetic counselor. See Appendix #2 “How can a Genetic Counselor Address My Concerns”

NBS Registry The Network has established an electronic NBS Registry for patients referred, diagnosed, and treated through the Network. The network will measure, track and report on medical, developmental and behavioral health outcomes from birth to age 21. See Appendix #3 for Statewide Flow Diagram of the Network Model.

INITIAL Roles of PCPs and Network Coordinators: EVALUATION Upon receipt of an out of range result, a Network Coordinator will contact the newborn’s PCP or HBMP AND to obtain brief information about the baby and to discuss next steps. MANAGEMENT See Appendix #4 for Initial Intake Questions See Appendix #5 for Algorithm of PCP & Network Coordinator Roles See Appendix #6 Clarifying Differences Between Diagnostic and Screening Tests See Appendix #7 Guidance on Heel-stick Specimen Collection for PCP Offices Based on the results of the initial screen and/or subsequent diagnostic testing and clinical status, clinical care teams will determine which infants need to be connected with a subspecialist, and how soon. Families will meet with the appropriate specialist in genetics, endocrinology, hematology, neurology or immunology.

(continued…)

June2020/Newborn Screening/Rubin, Ellis Page 1 of 8

PCP Communication and documentation of NBS results with family: . PCP will have a conversation with parents regarding their child’s NBS results. This includes both in and out of range NBS results. . PCP will document NBS results in the child’s chart by the 1 month visit. This includes both in and out of range NBS results.

WHAT TO . History and physical exam EXPECT FROM . Review of NBS result and diagnostic testing, if completed THEIR FIRST . Initiation of treatment, if appropriate CLINICAL . Ascertain need for diagnostic testing CARE TEAM VISIT

LONG-TERM PCPs will remain an invaluable member of the care team as they continue to provide primary care. Long term MANAGEMENT management of the specific condition will be under the direction of the specialty clinical care team. The (Birth - Age 21) Network will remain involved to assist the care teams and families to ensure that all children receive best practice care, and that none are lost to follow up.

Many of the conditions have the potential to impact long term health and development. The Network model includes the reporting of developmental and behavioral health outcomes. To obtain this information, Network coordinators will be reaching out to PCPs at specified time intervals to obtain the results of developmental and behavioral health screenings that are already being performed in primary care. See Appendix #8 for PCP Network Interface: Schedule of Outreach Encounters.

See model of this integrated care system:

HOW TO Monday-Friday 8:30 am - 4:30 pm CONTACT THE Phone: 860.837.7870 NETWORK Fax: 860.837.7871 Email: [email protected] See Appendix #9 Should I Call the Network or the Program?

June2020/Newborn Screening/Rubin, Ellis Page 2 of 8

APPENDIX 1: WHAT DISORDERS ARE SCREENED FOR IN CT?

Amino Acid Disorders Organic Acid Conditions  Argininemia (ARG)  2-Methyl-3-Hydroxybutyric Acidemia (2M3HBA)  Argininosuccinic Aciduria (ASA)  2-Methylbutyrylglycinuria (2MBG)  Benign Hyperphenylalaninemia (H-PHE)  3-Hydroxy-3-Methylglutaric Aciduria (HMG)  Biopterin Defect in Cofactor Biosynthesis (BIOPT-BS)  3-Methylcrotonyl-CoA Carboxylase Deficiency (3-MCC)  Biopterin Defect in Cofactor Regeneration (BIOPT-REG)  3-Methylglutaconic Aciduria (3MGA)  Carbamoyl Phosphate Synthetase I Deficiency (CPS)  Beta-Ketothiolase Deficiency (BKT)  Citrullinemia, Type I (CIT)  Ethylmalonic Encephalopathy (EME)  Citrullinemia, Type II (CIT II)  Glutaric Acidemia, Type I (GA-1)  Classic Phenylketonuria (PKU)  Holocarboxylase Synthetase Deficiency (MCD)  Homocystinuria (HCY)  Isobutyrylglycinuria (IBG)  Hypermethioninemia (MET)  Isovaleric Acidemia (IVA)  Maple Syrup Urine Disease (MSUD)  Malonic Acidemia (MAL)  Ornithine Transcarbamylase Deficiency (OTC)  Methylmalonic Acidemia (Cobalamin Disorders) (Cbl  Tyrosinemia, Type I (TYR I) A,B)  Tyrosinemia, Type II (TYR II)  Methylmalonic Acidemia (Methymalonyl-CoA Mutase  Tyrosinemia, Type III (TYR III) Deficiency) (MUT)  Methylmalonic Acidemia with Homocystinuria (Cbl C, D, Endocrine Disorders F)  Congenital Adrenal Hyperplasia (CAH) (Spanish version)  Propionic Acidemia (PROP)  Primary Congenital Hypothyroidism (CH) (Spanish version) Other Genetic Disorders  Adrenoleukodystrophy (ALD) Fatty Acid Oxidation Disorders  Biotinidase Deficiency (BIOT) (Spanish version)  2,4 Dienoyl-CoA Reductase Deficiency (DE RED)  Classic Galactosemia (GALT) (Spanish version)  Carnitine Acylcarnitine Translocase Deficiency (CACT)  Formiminoglutamic Acidemia (FIGLU)  Carnitine Palmitoyltransferase I Deficiency (CPT-IA)  Galactoepimerase Deficiency (GALE)  Carnitine Palmitoyltransferase Type II Deficiency (CPT-II)  Galactokinase Deficiency (GALK)  Carnitine Uptake Defect (CUD)  Glutaric Acidemia, Type II (GA-2) Immunology  Long-Chain L-3 Hydroxyacyl-CoA Dehydrogenase  Severe Combined Immunodeficiency (SCID) Deficiency (LCHAD)  T-cell Related Lymphocyte Deficiencies  Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCAD) Neurology  Medium/Short-Chain L-3 Hydroxyacyl-CoA  Spinal Muscular Strophy (SMA) Dehydrogenase Deficiency (M/SCHAD)  Short-Chain Acyl-CoA Dehydrogenase Deficiency (SCAD) May be identified by NBS  Trifunctional Protein Deficiency (TFP)  Duarte Galactosemia  Very Long-Chain Acyl-CoA Dehydrogenase Deficiency  Carrier Identification (VLCAD) Coming Soon Hemoglobin Disorders  Mucopolysaccharidosis Type 1 (MPS-1)  Hemoglobinopathies (Var Hb)  Pompe  S, Beta-Thalassemia (Hb S/ßTh)  S, C Disease (Hb S/C)  Sickle Cell Anemia (Hb SS)

Please note: Cystic Fibrosis, Critical Congenital Heart Disease, and Hearing Loss ARE screened for in CT. However, they ARE NOT addressed by the Network.

June2020/Newborn Screening/Rubin, Ellis Page 3 of 8

APPENDIX 2: HOW CAN A GENETIC COUNSELOR SUPPORT YOUR PRACTICE & FAMILIES?

Genetic counselors are healthcare professionals who have specialized education in genetics and counseling. Genetic counselors can work with families and their healthcare providers to understand complex genetic information and help them make informed decisions on their healthcare based on genetic testing and family history.

Their role is to help patients and their families understand and make decisions about genetic testing, genetic conditions and related issues. These may include medical and emotional concerns for you and your family. Genetic counselors can provide information and answer questions about:

 The science behind genetic conditions  The chance for genetic disease in you or other family members  Genetic testing (benefits and limitations)  Management and prevention of genetic conditions  Available resources / support

APPENDIX 3: STATEWIDE FLOW DIAGRAM OF THE NETWORK MODEL

June2020/Newborn Screening/Rubin, Ellis Page 4 of 8

APPENDIX 4: INITIAL INTAKE QUESTIONS  Have you seen the newborn? (yes/no)  Where is the newborn now? (home/hospital/emergency room/clinic/other)  Are the parent(s) aware of the screening result yet? (yes/no/unknown)  Does the newborn have nay family history relevant to the condition for which they had a positive screen? (yes/no/unknown)  Has the newborn regained birth weight? (yes/no/unknown)  Were there any delivery concerns? (yes/no/unknown)  Does the newborn have any feeding issues? (yes/no/unknown)  Does the newborn have vomiting concerns? (yes/no/unknown)  Is the newborn breastfeeding? (yes/no/unknown)  Are any social services like DCF involved with this family? (yes/no/unknown)  Does patient have difficulty accessing or affording transportation? (yes/no/unknown)  Who lives at home with the newborn?  Preferred follow up location? (Connecticut Children’s Medical Center/Yale New Haven Hospital/other)  Preferred lab for confirmatory blood work?

June2020/Newborn Screening/Rubin, Ellis Page 5 of 8

APPENDIX 5: PCP & NETWORK COORDINATOR ROLES IN INITIAL EVALUATION & MGMT

June2020/Newborn Screening/Rubin, Ellis Page 6 of 8

APPENDIX 6: CLARIFYING DIFFERENCES BETWEEN DIAGNOSTIC & SCREENING TESTS Screening test results guide the doctor in determining whether or not to ask for a diagnostic testing. In other words, a positive screening test indicates the possibility that the infant may have the suspected condition and this can then be confirmed by a diagnostic test. Diagnostic tests are usually performed after a positive screening test to establish a definitive diagnosis.

Screening Tests Diagnostic Tests Purpose To detect potential disease indicators To establish presence/absence of disease

Target Large numbers of asymptomatic, but Symptomatic individuals to establish diagnosis, or Population potentially at risk individuals asymptomatic individuals with a positive screening test

Test Method Simple, acceptable to patients and May be invasive, and expensive, but justifiable as staff necessary to establish diagnosis

Positive Result Generally chosen towards high Chosen towards high specificity (true negatives). More Threshold sensitivity not to miss potential disease weight given to accuracy and precision than to patient acceptability

Positive Result Essentially indicates suspicion of Result provides a definite diagnosis disease (often used in combination with other risk factors) that warrants confirmation

Cost Cheap, benefits should justify the costs Higher costs associated with diagnostic test may be since large numbers of people will justified to establish diagnosis need to be screened to identify a small number of potential cases

APPENDIX 7: GUIDANCE ON HEEL-STICK SPECIMEN COLLECTION FOR PCP OFFICES

https://portal.ct.gov/-/media/DPH/NBS-Forms-and-Documents/Heel-stick-specimens-for-PCPs.pdf?la=en

June2020/Newborn Screening/Rubin, Ellis Page 7 of 8

APPENDIX 8: PCP NETWORK INTERFACE: SCHEDULE OF OUTREACH ENCOUNTERS

Age at UNIVERSAL TARGETED Network SCREENING: SCREENING Type of Tool Intake Questions Outreach (Use below tools or (Use below tools or equivalent) equivalent) ASQ Developmental (parent)  Was the screening tool 32 months M-CHATs completed? Autism (parent) (18 & 32 months)  Was the result out-of- Social/Emotional 4 years Preschool PSC range? parent) o If yes, was the child 9 years PSC-17 Mental Health (parent) connected to care? PSC-17 Mental Health (parent)

>12 years PHQA Depression (teen) (targeted outreach: CRAAFT Substance Use (teen) 15 years) GAD-7 Anxiety (teen) SCARED Anxiety (teen)

APPENDIX 9: SHOULD I CALL THE NETWORK OR THE PROGRAM?

June2020/Newborn Screening/Rubin, Ellis Page 8 of 8