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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

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newborn screening ontario s expanded screening program

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



  • 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
Newborn Screening – What’s new?
  • Previously:
    • PKU, congenital hypothyroidism, hearing loss
  • Beginning April 2006:
    • Progressive expansion to 29primary disorders
    • NBS includes hearing screening but, the focus of this module will be on metabolic, endocrine and hematologic conditions
expanded nbs 29 conditions
Expanded NBS – 29 conditions
  • 20 inborn errors of metabolism
  • 3 hemoglobinopathies
  • 2 endocrine disorders
    • Congenital hypothyroidism
    • Congenital adrenal hyperplasia
  • 3 other metabolic disorders
    • Cystic fibrosis
    • Galactosemia
    • Biotinidase deficiency
  • Hearing loss
benefits of nbs
Benefits of NBS
  • Identification
  • Early intervention
  • Reduced morbidity & mortality
  • Family planning
risks of nbs
Risks of NBS
  • Parental anxiety (false positives)
  • Missed diagnosis (false negatives)
  • The right ‘not to know’
  • Unanticipated outcomes
  • Labelling – diagnosis of benign conditions
nbs how where is it done
NBS: how & where is it done?
  • Method: Heel prick
  • Sample collection: newborn screening card
  • Testing Location: Newborn Screening Ontario (NSO) at Children’s Hospital of Eastern Ontario (CHEO)
  • Transportation: NBS cards are sent via courier service
timing of testing
Timing of Testing
  • Acceptable samples
    • between 1 day (24 hours) and 7 days after birth
  • Best time for sample:
    • between 2 days (48 hours) and 3 days (72 hours) after birth
  • If tested before 1 day (24 hours) of age, REPEAT the test within 5 days*
  • If the baby is >5 days, screening is still available
    • Contact NSO program for details

* Repeat sample within 5 days has been the Ontario standard of care since 2001

special considerations
Special Considerations
  • Prematurity or illness
    • If <37 weeks - collect specimen at 5-7 days old
    • Indicate this on NBS card
    • May have false positive test results
  • Total Parenteral Nutrition (TPN)
    • Certain amino acids and organic acids will be elevated
    • Indicate this on NBS card
  • Transfusion
    • Disorders may be missed
    • Ideally complete card and obtain sample before transfusion
  • Early discharge
    • If prior to 24 hours, parents should be informed that a repeat sample must be done

What makes a good spot?See Newborn Screening Ontario website – educational resource for blood spot collection:

nbs for your information
NBS: For your information
  • Location
    • Newborn Screening Ontario at CHEO
  • 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

Parents will ask you about NBS

screen positive results
Screen Positive Results
  • Screen positive means:
    • Further testing is required to confirm the diagnosis
    • Does NOT mean that the infant is affected
  • NSOwillimmediately 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 ms schulze et al pediatrics 2003
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
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 conditions17
Expanded NBS – 29 conditions
  • 20 inborn errors of metabolism
    • 9 organic acid disorders
    • 5 fatty acid oxidation disorders
    • 6 amino acid disorders
  • 3 hemoglobinopathies
  • 2 endocrine disorders
  • 3 other metabolic disorders
  • Hearing loss
inborn errors of metabolism
Inborn errors of metabolism
  • Rare
  • Usually autosomal recessive inheritance
    • consanguinity is more common
  • Symptoms secondary to a problem in the metabolic pathway
  • Usually not significant dysmorphism
  • Early recognition and intervention can be lifesaving
frequency of inborn errors of metabolism iem using ms ms tandem mass spectrometry
Frequency of Inborn Errors of Metabolism (IEM) using MS/MS Tandem Mass Spectrometry

(*) Does not include tyrosinemia type 1 and 2

organic acid disorders
Organic Acid Disorders
  • Isovaleric acidemia (IVA)
  • Glutaric acidemia type 1 (GA1)
  • HMG-CoA lyase deficiency (HMG)
  • Multiple carboxylase deficiency (MCD)
  • Methylmalonic acidemia (MMA)
  • Methylmalonic acidemia (MUT, Cbl)
  • 3-methylcrotonyl-CoA carboxylase (3MCC) deficiency
  • Propionic acidemia (PA)
  • Β-ketothiolase deficiency (BKT)
organic acid disorders21
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
    • sepsis, death
  • Treatment
    • Low protein diet / restrict amino acids,
    • Supplements: carnitine, biotin, riboflavin, glycine
    • Avoid fasting
fatty acid oxidation disorders
Fatty Acid Oxidation Disorders
  • Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency
  • Very long-chain acyl-CoA dehydrogenase deficiency (VLCAD)
  • Long-chain L-3-OH acyl-CoA dehydrogenase deficiency (LCHAD)
  • Trifunctional protein deficiency (TFP)
    • catalyzes 3 steps in mitochondrial beta-oxidation of fatty acids
  • Carnitine uptake defect (CUD)
disorders of fatty acid oxidation
Disorders of Fatty Acid Oxidation

What are disorders of fatty acid oxidation?

Breakdown of fatty acids in mitochondria is an essential part of body’s ability to produce energy

Disorder: inability to break down fatty acids


Decompensate with any catabolic stress

fever, fasting, intercurrent illness

Hypoketotic hypoglycemia, liver, muscle, heart disease

Lethargy, seizures, coma, sudden death (SIDS)


Avoid fasting

IV glucose when ill to prevent hypoglycemia

Frequent feeding

amino acid disorders
Amino Acid Disorders

Phenylketonuria (PKU)

Maple syrup urine disease (MSUD)

Tyrosinemia type 1 (TYR 1)

Common in French Canadians

Homocystinuria (HCY)

Citrullinemia (CIT)

Argininosuccinic acidemia (ASA)

amino acid disorders25
Amino Acid Disorders
  • What are amino acid disorders?
    • Occur when the body cannot either metabolize or produce certain amino acids
    • Result in toxic accumulation of substances
    • Serious potentially preventable effects on health and development including death
  • Symptoms (untreated) example PKU
    • Hyperphenylalaninemia (neurotoxic)
    • Microcephaly, epilepsy, mental retardation, behaviour problems
  • Treatment
    • Diet: reduce phenylalanine, low protein, supplement cofactors or essential amino acids
expanded nbs 29 conditions26
Expanded NBS – 29 conditions
  • 20 inborn errors of metabolism
  • 3 hemoglobinopathies
  • 2 endocrine disorders
    • Congenital hypothyroidism
    • Congenital adrenal hyperplasia
  • 3 other metabolic disorders
  • Hearing loss
endocrine disorders ch
Congenital Hypothyroidism (CH)

What is CH?

inadequate thyroid hormone production

Anatomic defect in gland, dyshormogenesis, iodine deficiency


MR, ↓ growth & bone maturation, neurologic problems: spasticity, gait abn, dysarthria, autistic behaviour


Diagnosis made before 13 days to prevent symptoms

Thyroid hormone replacement

Endocrine Disorders: CH
endocrine disorders cah
Endocrine Disorders: CAH

Congenital Adrenal Hyperplasia (CAH)

  • What is CAH?
    • Impaired synthesis of cortisol by the adrenal cortex leads to ↑↑↑ androgen biosynthesis
    • Inability to maintain adequate energy & blood glucose level to meet stress of injury & illness
  • Symptoms
    • Virilization (♀ ambiguous genitalia), precocious puberty, infertility, short stature
    • Renal salt wasting leads to FTT, vomiting, dehydration, hypotension, hyponatremia, & hyperkalemia
  • Treatment
    • Glucocorticoid replacement therapy
expanded nbs 29 conditions29
Expanded NBS – 29 conditions

20 inborn errors of metabolism

3 hemoglobinopathies

Sickle cell disease (Hb-SS)

SC disease (Hb-SC)

Sickle beta thalassemia

Other hemoglobinopathies may reported if clinically significant

2 endocrine disorders

3 other metabolic disorders

Hearing loss

sickle cell disease
Sickle Cell Disease
  • What is sickle cell disease? (Hb SS)
    • Change in the shape of the betaglobin component of the hemoglobin moleculethat interferes with hemoglobin’s ability to carry oxygen
  • Symptoms
    • Painful vaso-occlusive crises, hemolytic anemia, frequent infections, tissue ischemia, chronic organ dysfunction
  • Diagnosis
    • Quantitative hemoglobin electrophoresis and/or Molecular analysis
    • Do not rely on solubility testing methods (Sickledex etc)
  • Treatment
    • Prophylactic penicillin (84% reduction in infection)
    • Vaccinations (pneumococcal, influenza)
    • Aggressive treatment of fever and dehydration
expanded nbs 29 conditions31
Expanded NBS – 29 conditions

20 inborn errors of metabolism

3 hemoglobinopathies

2 endocrine disorders

3 other metabolic disorders

Biontinidase deficiency


Cystic fibrosis

Hearing loss

other disorders biotinidase deficiency
Other Disorders:Biotinidase deficiency
  • What is biotinidase deficiency?
    • Biotinidase is responsible for recycling biotin – a cofactor for 4 dependant carboxylases
  • Symptoms
    • Metabolic ketoacidosis, organic aciduria, mild hyperammonemia
    • Seizures, hypotonia, ataxia, developmental delay, vision problems, hearing loss, cutaneous abnormalities
  • Treatment
    • 5-10mg of oral biotin per day, long term treatment prevents all symptoms
other disorders galactosemia
Other Disorders: Galactosemia
  • What is galactosemia?
    • Lactose is main sugar in breast milk & infant formulas
    • Metabolized into glucose and galactose in the intestine
    • Unable to break down galactose
  • Symptoms
    • Feeding problems, FTT, bleeding, infection, liver failure, cataracts, mental retardation, death
  • Treatment
    • 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
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
case 1
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
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 138








Case 1

British / French

Irish / German


Prost Ca Dx 74







MI – died 69
















13 months

11 wk


A& W

7 5



case 139
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
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
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: developmental & behavioural disabilities, chronic muscle weakness, seizures, cerebral palsy, ADD
mcad a preventable cause of sids
MCAD: a preventable cause of SIDS
  • Sudden death is the first symptom in 25% of MCAD cases
  • Early diagnosis and treatment of MCAD can prevent sudden death
  • MCAD responsible for ~1% of SIDS cases, all FAO disorders ~4%
    • Opdal et al. Pediatrics 2004;114:506-512
mcad management
MCAD: Management
  • Infants require frequent feedings
    • 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
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
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
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
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
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
Provincial Educational Materials
  • MOHLTC INFOline at 1-866-532-3161/TTY: 1-800-387-5559
  • Contact Newborn Screening Ontario:
    • Telephone: 613-738-3222
  • Educational materials are available free-of-charge and can be ordered through or by calling 1-877-844-1944

Disorder Fact Sheets

Parent Fact

  • Newborn Screening Ontario Website:

  • March of Dimes:

  • Genetests:

  • National Newborn Screening & Genetics Resource Center:

  • Pediatrix – US private lab offering NBS

  • American College of Medical Genetics – fact sheets

  • American Academy of Pediatrics – fact sheets;118/3/e934

  • American Academy of Family Physicians – Information & resources

  • Ontario Medical Association – Important changes to NBS in Ontario

the genetics education project committee
June C Carroll MD CCFP


Sean Blaine MD CCFP

Mary Jane Esplen PhD RN

Sandra Farrell MD FRCPC FCCMG

Judy Fiddes


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


Sherry Taylor PhD FCCMG

Brenda Wilson BSc MB ChB MSc MRCP(UK) FFPH

The Genetics Education Project Committee
  • Ontario Ministry of Health and Long Term Care, News release 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
  • 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.
  • Bellis MA, Hughes K, Hughes S, Aston JR. Measuring parent discrepancy and its public health consequences. J Epidemiol Community Health 2005; 59: 749-754.
  • Ontario Ministry of Health and Long Term Care, Newborn Screening website:
  • NCCLS (National Committee for Clinical Laboratory Standards now known as CLSI – Clinical Laboratory Standards Institute) LAR-A3 “Blood collection on filter paper for neonatal screening programs: approved standard, third edition.”
  • “Simple Spot Check” 04/03/02 Lit. #718 produced by Schleicher & Schuell BioScience Inc. 10 Optical Ave, Keene NH 03431 USA. Scheicher & Schuell BioScience GmbH P.O. Box 1160, D-37582 Dassel, Germany.
  • Waston MS, Mann MY, Lloyd-Puryear MA, Rinaldo P, Howell RR. Executive summary: Newborn screening panel and system. Genet Med 2006; 8 (5, supplement): 1s-11s.
  • Schulze A, Lindner M, Kohlmuller D, Olgemoller K, Mayatepek E, Hoffmann GF. Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: Results, outcome and implications. Pediatrics 2003; 111:1399-1406.
  • Applegarth Da, Toone JR, Lowry RB. Incidence of inborn errors of metabolism in British Columbia, 1969 – 1996. Pediatrics 2000: 105:e10-e16.
  • Frazier DM, Millington DS, McCandless SE, Keoberl DD, Weavil Sd, Chaing SH, Muenzer J. The tandem mass spectrometry newborn screening experience in North Carolina: 1997-2005. J Inhert Metab Dis 2006; 29:76-85.
  • Marsden D, Larson C, Levy Hl. Newborn screening for metabolic disorders. J Pediatr 2006; 148:577-584.
  • Centers for Disease Control and Prevention. Impact of expanded newborn screening – United States 2006 Morbidity and Mortality Weekly Report. 2008;57:1012-1015.
  • Seashore MA. Genetest Reviews: The organic acidemias: An overview. Last updated 03 July 2007.
  • Ogier de Baulny HO, Saudubray JM. Branched-chain organic acidurias. Semin Neonatol. 2002; 7:65-74.
  • Venditti CP. Genetests Reviews: Methylmalonic Acidemia. Last updated 18 January 2007.
  • Korman SH. Inborn errors of isoleucine degradation: A review. Mol Genet Metab. 1006: 89:289-299.
  • Gibson KM, Breuer J, Kiaser K, Nylan WL, McCoy EE, Ferreira P, Greene CL, Blitzer MG, Shapira E, Reverte F, Conde C, Bagnell P, Cole DEC. 3-hydroy-3-methylglutaryl-coenzyme A lyase deficiency: Report of five new patients. J Inhert Metab Dis 1988; 11:76-87.
  • Roth KS. Holocarboxylase Deficiency. Last updated 31 August 2007.
  • Angelini C, Federico A, Reichmann H, Lombes, Chinnery P, Turnbull D. Task force guidelines handbook: EFNS guidelines on diagnosis and management of fatty acid mitochondrial disorders. Eur J Neurol. 2006; 13:923-929.
  • Saudubray JM, Martin D, deLonlay P, Touati G, Poggi-Travert F, bonnet D, Jouvet P, Boutron M, Slama A, Vianey-saban C, Bonnefont JP, Rabier, Kamoun P, Brivet M. Recognition and management of fatty acid oxidation defects: A series of 107 patients. J Inherit Metabo Dis. 1999; 22:488-502.
  • Hellekson KL; National Institutes of Health. Am Fam Physician. 2001 63:1430 1432.
  • National Institutes of Health Consensus Development Panel. National institutes of Health consensus development conference statement: Phenylketonuria screening and management, October 16-18 2000. Pediatrics 2001; 108: 972-982.
  • Mitchell JJ, Scriver CR. Genetests Reviews: Phenylalanine hydroxylase deficiency. Last updated 29 march 2007.
  • Morton DH, Strauss KA, Robinson DL, Puffenberger EG, Kelley RI. Diagnosis and treatment of maple syrup urine disease: A study of 36 patients. Pediatrics 2002; 109:999-1008.
  • Le Roux C, Murphy E, Liblurn M. The longest surviving patient with classical maple syrup urine disease. J Inherit Metab Dis 2006; 29:190-194.
  • Strauss KA, Puffenberger EG, Morton DH. Genetests Reviews: Maple Syrup Urine Disease. Last updated 30 January 2006.
  • Scott CR. The genetic tyrosinemias. Am J Med Genet Part C Semin Med Genet 2006; 142C:121-126.
  • Russo PA, Mitchell GA, Tanguay RM. Tyrosinemia: a review. Pediatr Dev Pathol. 2001; 4:212-221.
  • Sniderman King L, Trahms C Scott R. Genetests Reviews: Tyrosinemia Type I. Last updated 31 October 2008.
  • Walter JH, Wraith JE, White FJ, Bridge C, Till J. Strategies for the treatment of cystathionine β-synthase deficiency: the experience of the Wilink Biochemical Genetics Unit over the past 30 years. Eur J Pediatr. 1998; 157(Suppl 2):s71-s76.
  • De Franchis R, Sperendeo MP, Sebastio G, Andria G. The Italian Study group on Homocystinuria. Clinical aspects of the cynstathionine β-synthase deficiency: how wide is the clinical spectrum? Eur J Pediatr. 1998; 157(Suppl 2):s67-s70.
  • Picker JD. Levy HL. Genetests Reviews: Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency. Last updated 29 March 2006.
  • Summar M, Tuchman M. Proceeding of a consensus conference for the management of patients with urea acid cycle disorders. J Pediatr. 2001; 138(Suppl1):s6-s10.
  • The Urea Cycle Disorders Conference Group. Consensus statement from a conference for the management of patients with urea cycle disorders. J Pediatr. 2001; 138(Suppl1):s1-s5.
  • Summar, ML. Genetests Reviews: Urea Cycle Disorders Overview. Last updated 11 August 2005.
  • Thoene, JG. Genetests Reviews: Citrullinemia Type I. Last updated 02 June 2009.
  • Roth KS. Argininosuccinate Lyase Deficiency. Last Updated 24 March 2009. - free registration is required. If you are already registered the direct link is:
  • American Academy of Pediatrics; Rose SR; Section on Endocrinology and Committee on Genetics, American Thyroid Association; Brown RS; Public Health Committee, Lawson Wilkins Pediatric Endocrine Society; Foley T, Kaplowitz PB, Kaye CI, Sundararajan S, Varma SK. Update of newborn screening and therapy for congenital hypothyroidism. Pediatrics. 2006 Jun;117:2290-2303.
  • Postellon D, Bourgeois MJ, Varma S. eMedicine: Congenital Hypothyroidism. Last Updated: 23 August 2006
  • Merke DP, Bornstein SR. Congenital adrenal hyperplasia. Lancet. 2005; 365: 2125-2136.
  • New MI, Nimkarn S. GeneTests Reviews: Congenital Adrenal Hyperplasia, last update 7 September 2006.
  • Wethers DL. Sickle cell disease in childhood: Part II. Diagnosis and treatment of major complications and recent advances in treatment. Am Fam Physician. 2000; 62: 1309-1314.
  • Bender MA. GeneTests Reviews: Sickle cell Disease, last update 7 March 2006.
  • Wolf B. Worldwide survey of neonatal screening for biotinidase deficiency. J Inherit Metab Dis. 1991; 14:923-927.
  • Wolf B. GeneTests Reviews: Biotinidase Deficiency, last update 25 September 2008.
  • Bosch AM. Classical galatosemia revisited. J Inherit. Metab. Dis. 2006; 29:516-529.
  • Schweitzer-Krantz S. Early diagnosis of inherited metabolic disorders improving outcome: the controversial issue of galactosemia. Eur J Pediatr. 2003; 162:s50-s503.
  • Elsas LJ. GeneTests Reviews: Galactosemia, last update 27 September 2007.
  • Moskowitz SM, Gibson RL, Sternen DL, Cutting GR. Genetests Reviews: CFTR-Related Disorders. Last updated 19 February 2008.
  • Yankaskas JR, Marshall BC, Sufian B, Simon RH, Rodman D. Cystic fibrosis adult care: Consensus conference report. Chest 2004;125:s1-s39.
  • Saiman L, Siegel J. Infection control recommendations for patients with cystic fibrosis: Microbiology, important pathogens and infection control to prevent patient to patient transmission, Cystic fibrosis consensus conference on infection control participants. Am J Infection Control 2003; 31:s1-s62.
  • Cystic Fibrosis Trust Clinical Standards and Accreditation Group. Standards of care for children and adults with cystic fibrosis in the UK. May 2001.
  • Matern D, Rinaldo P. GeneTests Reviews: Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency. Last update 3 February 2005.
  • Opdal SH, Rognum TO. The sudden infant death gene: does it exist? Pediatrics 2004; 114:506-512.
  • Grosse SD, Rosenfeld M, Devine OJ, Lai HJ, Farrell PM. Potential impact of newborn screening for cystic fibrosis on child survival: A systematic review and analysis. J Pediatr 2006;149:362-366.
  • Dankert-Roelse JE, Me´relle ME.Review of outcomes neonatal screening for cystic fibrosis verses non-screening in Europe. J Pediatr 2005; 147:s15-20.
  • Southern KW, Mérelle MME, Dankert-Roelse JE, Nagelkerke A. Newborn screening for cystic fibrosis (Review). Cochrane Database of Systematic Reviews, Issue 1, 2009.