Newborn Screening: Ontario’s Expanded Screening Program Prepared by: June C Carroll MD, CCFP, FCFP Sydney G. Frankfort Chair in Family Medicine Mount Sinai Hospital, University of Toronto Andrea Rideout MS, CGC, CCGC Certified Genetic Counsellor Project Manager – The Genetics Education Project Funded by: Ontario Women’s Health Council Version: May 2010
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Newborn Screening: Ontario’s Expanded Screening Program
Prepared by: June C Carroll MD, CCFP, FCFPSydney G. Frankfort Chair in Family MedicineMount Sinai Hospital, University of Toronto
Andrea Rideout MS, CGC, CCGCCertified Genetic CounsellorProject Manager – The Genetics Education
Project
Funded by: Ontario Women’s Health Council
Version: May 2010
AcknowledgmentsReviewers: Members of The Genetics Education Project Ontario Newborn Screening Program: Dr. Michael
Geraghty, Mireille Cloutier MSc., Christina Honeywell MSc., Sari Zelenietz MSc, Shelley Kennedy MSc.
Funded by: Ontario Women’s Health Council as part of its funding to The Genetics Education Project
* Health care providers must use their own clinical judgment in addition to the information presented herein. The authors assume no responsibility or liability resulting from the use of information in this presentation.
Newborn Screening – What’s new?
Previously: PKU, congenital hypothyroidism, hearing loss
Beginning April 2006: Progressive expansion to 29 primary disorders NBS includes hearing screening but, the focus of
this module will be on metabolic, endocrine and hematologic conditions
Newborn Screening Ontario at CHEO http://www.newbornscreening.on.ca
Tandem Mass Spectrometry Allows screening for multiple conditions concurrently Same cost to screen for one condition as multiple Increased sensitivity and specificity Screening for some metabolites can give information
about several diseases Educational materials
MOH & NSO have developed materials for the public and healthcare providers
Further testing is required to confirm the diagnosis Does NOT mean that the infant is affected
NSO will immediately notify regional treatment centre Regional treatment centre will notify the infant’s
healthcare provider and/or parents and arrange confirmatory testing
If diagnosis is confirmed, regional treatment centre will provide management counselling & follow up
Report will be mailed to referring hospital, provided that correct information is completed on the screening card.
Results of Expanded NBS by MS/MSSchulze et al. Pediatrics 2003
250,000 neonates screened for 23 inborn errors of metabolism 106 newborns with confirmed metabolic disorder
70 required treatment Overall prevalence of metabolic disorder = 1/2400 825 false positives (0.33% false positive rate) Overall specificity = 99.67% (PPV = 11.3%) Overall sensitivity = 100% for classic forms of disorders
= 92.6% for variants 61 /106 were judged to have benefited from screening
and treatment 58% of true positives 1/4100 newborns
Negative Results
Results will go to: Submitting health care professional/hospital
If you suspect that an infant or child has symptoms of a screened condition and their NBS results are negative – please refer to the appropriate specialist for evaluation NBS panel does not screen for every metabolic condition NBS is a screening test – not diagnostic
Expanded NBS – 29 conditions 20 inborn errors of metabolism
Organic Acid Disorders What are organic acid disorders?
Body cannot metabolize certain amino acids and fats Accumulation of organic acids in blood and urine Serious potentially preventable effects on health and
development, including death Symptoms
acute encephalopathy, vomiting, metabolic acidosis, ketosis, hyperammonemia, hypoglycemia, coma
dehydration, failure to thrive, hypotonia, global developmental delay
Lactose-galactose-restricted diet must be started in first 10 days of life to prevent symptoms
Even with treatment - ↑ developmental delay, speech problems, abn motor function, premature ovarian failure
Other Disorders: Cystic fibrosis What is cystic fibrosis?
Due to mutations in the CFTR gene which is responsible for chloride regulation and other transport pathways.
Symptoms Chronic sinopulmonary disease Gastrointestinal/nutritional abnormalities Azoospermia (males) Salt loss syndrome Shortened life span – but improving with treatment
Treatment Pulmonary: oral, inhaled, or IV antibiotics, bronchodilators, anti-
inflammatory agents, mucolytic agents, chest physiotherapy Gastrointestinal: Nutritional therapy special formulas for weight
gain via improved intestinal absorption, and additional fat-soluble vitamins & zinc to prevent deficiencies
Cases
Case 1 Carmen and George bring Amy into your
office for 1 week visit Healthy 1 week old Parents worried re risk of SIDS First daughter died of SIDS 5 years earlier Carmen’s cousin died of SIDS at 18
months
Case 1: Amy – 5 days old You receive a call that Amy has screened positive
for MCAD deficiency Medium chain acyl-CoA dehydrogenase deficiency
You ask Carmen and George to bring her in that day
Healthy 5 day old Parents worried about risk of SIDS First daughter died of SIDS 5 years earlier Carmen’s cousin died of SIDS months
Case 1
–
39A&W
37Schizophrenic
35GeorgeA&W
25A&W
29A&W
11 wkAmy A& W
SIDS
79Prost Ca Dx 74
72A&W
32CarmenA&W
British / FrenchIrish / German
SIDS13 months
49Accident
7 5A&W A&W
PS S
Legend
Prostatecancer
SIDS
Case 1
Amy’s expanded newborn screening report is the following:
Screen positive for medium chain acyl-CoA deficiency
MCAD (medium chain acyl-CoA deficiency) Incidence
1 in 4,900 – 1 in 17,000 most prevalent in North Europeans
Inheritance Autosomal recessive (Gene: ACADM)
Enzyme Medium-chain acyl-coenzyme A dehydrogenase
Function Mitochrondrial fatty acid β-oxidation Required for energy and ketone body production Important during prolonged fasting
MCAD: Symptoms Usually presents at 3 to 24 months Triggered by fever, illness, or fasting Symptoms:
Hypoglycemia, vomiting Lethargy → coma → death Encephalopathy, respiratory arrest, hepatomegaly,
seizures Long term outcomes after a clinical episode:
Formulas containing medium chain triglycerides as the primary source of fat should be avoided
Avoid prolonged fasting, hypoglycemia Aggressive treatment of illness often with
IV fluids especially when vomiting
Case 2 Angela receives a call from Newborn
Screening Ontario for a repeat NBS sample for her newborn, Liam.
Angela comes to your office for a routine newborn visit.
Liam’s newborn screening report: Positive, for cystic fibrosis Category B
IRT>96% DeltaF508 (one mutation identified)
What are the next steps? ~1 in 40 chance of being affected with CF Sweat chloride test is next step
3 possible results: Abnormal – affected with CF Borderline – inconclusive, follow up with specialist Normal – unaffected, but carrier of CF
Blood work: Confirmatory genetic testing
Genetic counselling is recommended
NBS for cystic fibrosis Some evidence that early identification leads to
better outcomes Lower incidence of malnutrition Improved growth (height, weight) Better lung function parameters at 10 years of age
no evidence of difference in adulthood ?improved survival by 10 years of age ?reduced mortality
Identification enables family planning
Liam’s results Sweat test results – Normal Liam is a carrier of CF He will not develop CF Parents Angela and James have genetic
counselling… Angela – carrier of CF deltaF508 mutation + normal gene James – carrier of CF R553X mutation + normal gene Risk to have a child affected with CF
25% with each pregnancy
NBS – Bottom Line Offer newborn screening Discuss the benefits Discuss how testing is done Discuss timing Repeat sample sometimes required Discuss difference between screening and
diagnostic test Discuss possible results Answer questions/brochure
Provincial Educational Materials www.health.gov.on.ca/newbornscreening MOHLTC INFOline at 1-866-532-3161/TTY: 1-
American Academy of Pediatrics – fact sheetshttp://aappolicy.aappublications.org/cgi/content/abstract/pediatrics;118/3/e934
American Academy of Family Physicians – Information & resources
http://www.aafp.org/afp/2008/0401/p987.html Ontario Medical Association – Important
changes to NBS in Ontariohttp://www.oma.org/Health/newborn/06newborn.asp
The Genetics Education Project Committee June C Carroll MD CCFP Judith Allanson MD FRCP
FRCP(C) FCCMG FABMG Sean Blaine MD CCFP Mary Jane Esplen PhD RN Sandra Farrell MD FRCPC
FCCMG Judy Fiddes Gail Graham MD FRCPC
FCCMG Jennifer MacKenzie MD
FRCPC FAAP FCCMG Wendy Meschino MD
FRCPC FCCMG
Fiona Miller PhD Joanne Miyazaki Andrea L. Rideout MS CGC
CCGC Linda Spooner RN BScN Cheryl Shuman MS CGC Anne Summers MD
FCCMG FRCPC Sherry Taylor PhD FCCMG Brenda Wilson BSc MB
ChB MSc MRCP(UK) FFPH
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November 2, 2005: Ontario becomes national leader in newborn screening, New state-of-the-art testing program means that children will have a better start on life http://www.health.gov.on.ca/english/media/news_releases/archives/nr_05/nr_110205.html
2. Ontario Ministry of Health and Long Term Care, News release November 23, 2006: McGuinty government expands newborn screening, Screening for cystic fibrosis brings total number of tests to 28. http://www.health.gov.on.ca/english/media/news_releases/archives/nr_06/nov/nr_112306.html
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