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Expanded Newborn Screening
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Expanded Newborn Screening


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  • Since the implementation of the screening program by MOH, from jan 1995 to Dec 2005
  • Transcript

    • 1. Dr. Sanjida Ahmed (Director: Research) Eastern Biotech & Life Sciences DuBiotech Park, Dubai UAE Phone: 00971 4 3692061 Email: [email_address] Value of Metabolic Disorder Screening for Newborns
    • 2. Tyler Wayne’s Story
      • Tyler Wayne, was born 8 lbs. 3 oz. on May 1, 1998 as a healthy baby
      • At home he started vomiting violently and was admitted to the hospital again
      • He was lethargic and was not responsive to any stimulation and taken to emergency
      • Tyler died May 10 th , 1998 on mother’s day
      • The results of his newborn screening showed a positive result for galactosemia - a metabolic disorder or Inborn Error of Metabolism (IEM)
    • 3. Metabolic Disorders/ IEM
      • Metabolic disorders/IEMs are caused when the body is unable to break down nutrients, which then accumulate in the body and becomes toxic.
      • When the concentration of toxic build-up increase they cross the blood-brain barrier and this leads to delayed development, brain damage and, in some cases, even death.
      • Most infants with these disorders show no obvious signs of these disorders at birth, but the build-up can be rapid enough for the condition to become irreversible within a few weeks of birth.
    • 4. Reason behind these Disorders
        • These disorders follow an autosomal recessive inheritance pattern
        • Could skip generations
        • Parents are carriers
        • Happens when the two parents carry the gene 1:4 probability of having an affected child
    • 5. Newborn Screening
      • Newborn screening is the process of testing newborn babies for treatable genetic, endocrinologic, metabolic and hematologic diseases.
      • Screening is done to assist healthcare providers in detecting the existence of a number of treatable but clinically undiagnosed disorders, before symptoms occur, so that the most beneficial outcome can be achieved.
    • 6. Diagnosis of Metabolic Disorders is Challenging
      • The episodic nature of metabolic illness
      • The wide range of clinical symptoms that are associated with more common conditions like infection or sepsis.
      • The low incidence of these disorders
      • The consequent lack of experience among the pediatric sub-specialties
      • The need for specialty testing
    • 7. Early detection is very important
      • Affected babies are identified quickly before symptoms appear.
      • Cases of disease are not missed.
      • The number of false-positive results is minimized.
      • Early treatment can begin, that prevents the negative and irreversible health outcomes for affected newborns.
        • Most treatments are inexpensive and may involve the addition of a vitamin to the diet, hormone supplementation, avoidance of certain foods and chemicals or a dietary change.
    • 8. If screening is delayed
      • It could lead to lifelong complications:
      • Mental Retardation
      • Motor Impairment
      • Physical Disability
      GA 1 Screened GA 1 Not Screened GA 1 Screened
    • 9.
      • The newborn screen has to be done only once in a lifetime
      • Speeds diagnosis and saves costs
      • Healthy child instead of sick or mentally retarded child.
      Newborn tested 24 Hours after birth Confirmatory Test Start Treatment Positive Absence of 50 + treatable IEMs Positive Negative Negative Benefits of Newborn Screening for Metabolic Disorders
    • 10.
      • Anytime 24 hours AFTER birth (ideally within 1- 2 weeks).
      • Baby needs to be fed at least 2 - 3 times before the specimen is taken.
      • BEFORE developmental delay or other symptoms of mental retardation occur (best time is to screen a healthy baby).
      Time to do screening
    • 11.
      • Every Newborn (Routine screening)
      • High Risk
        • Unexplained deaths of siblings
        • Miscarriages & Aborted Fetuses
        • Exhibit symptoms of IEMs
        • Babies conceived by IVF
        • Babies in NICU
      • Sick Children
      Every Newborn needs to be Screened
    • 12. Sample from baby’s Heel 1. Puncture heel 2. Lightly touch filter paper to LARGE blood drop 3. Dry the sample & send to the laboratory
    • 13. Public Awareness of Metabolic Screening
      • Newborn screening began in South Carolina in the mid-1960’s with testing for phenylketonuria (PKU) only (
      • Over the years, the test panel has expanded with increased use of tandem mass spectrometry (MS/MS) in newborn screening applications
      • Now almost all states screen for more than 30 disorders.
      • (
      • Each year, at least 4 million babies in the United States are tested for these diseases, and severe disorders are detected in about 5,000 newborns. (
    • 14. Tandem Mass Spectrometry (MS/MS)
      • Mass Spectrometry means multiple analyte testing
      • Using Tandem Mass Spectrometry, multiple analytes are measured simultaneously
      • Quantitatively measures amino acids and acylcarnitines from dried blood spot specimens
      • Efficient and Economical
      • MS/MS is very precise
    • 15. Expanded Newborn Screening
      • ACYLCARNITINE PROFILE (Tandem Mass Spectrometry)
      • Fatty Acid Oxidation Disorders
      • Organic Acid Disorders
      • AMINO ACID PROFILE (Tandem Mass Spectrometry)
      • Amino Acid Disorders
      • Others
      • BIOCHEMICAL SCREENING (Enzyme Assay/Enz. immunoassay)
      • Galactosemia
      • Congenital Hypothyroidism
      • Congenital Adrenal Hyperplasia
      • G6PD Deficiency
      • Cystic Fibrosis
      • Biotinidase Deficiency
    • 16. Fatty Acid Oxidation Disorders (FAOD S)
      • Most common FA disorder—MCADD—is part of the current test panel
      • Expansion added eleven FAO disorders
      • Most are autosomal recessive disorders so risk of recurrence is 1:4 with each pregnancy
    • 17. Symptoms of Fatty Acid Oxidation Disorders
        • Hypoketotic hypoglycemia
        • Muscle weakness
        • Seizures
        • Sometimes cardiomyopathy
    • 18. Treatment of most Fatty Acid Oxidation Disorders
        • Avoid fasting
        • Immediate medical attention when unable to eat usual diet
        • Control type/amount of fat in diet depending upon the specific diagnosis
        • L-Carnitine if indicated
        • Cornstarch tube feeding at night if indicated
    • 19. Organic Acid (OA) Disorders
      • Expansion added the detection of 16 organic acid disorders
      • Most are autosomal recessive disorders so risk of recurrence is 1:4 with each pregnancy
      • A few sub-types are X-linked so only males are affected, but females may show milder symptoms
    • 20. Symptoms of most Organic Acid Disorders
        • Feeding problems (feed intolerance)
        • Seizures
        • Metabolic acidosis
        • Lethargy
    • 21. Treatment of most Organic Acid Disorders
        • Avoid fasting
        • Immediate medical attention when unable to eat usual diet
        • Control type/amount of protein in diet depending upon the specific diagnosis
        • Vitamin B12 if indicated
    • 22. Amino Acid (AA) Disorders
      • Most common AA disorder—PKU—is part of the current test panel
      • Expansion added additional 13 AA disorders
      • All are recessive genetic disorders so risk of recurrence is 1:4 with each pregnancy
      • Symptoms and treatments vary by disorder
    • 23. Biochemical Screening: One test-One Disorder (metabolic disorder screening that cannot be performed by Tandem Mass Spectrometry)
      • Galactosemia
      • Congenital Hypothyroidism
      • Congenital Adrenal Hyperplasia
      • G6PD Deficiency
      • Cystic Fibrosis
      • BIotinidase Deficiency
    • 24. Future Direction
      • Additional conditions are already under consideration for adding to screening panels: SCID, lysosomal storage disease, fragile X syndrome and other
      • Expansion of treatable disease criteria
      • Considering the identification of unaffected “carriers”, or conditions
    • 25. Status of Newborn Screening in UAE
      • The national neonatal screening program started by screening for phenylketonuria in January 1995 (MOH, 2006)
      • Screening for congenital hypothyroidism was introduced in January 1998 (MOH, 2006)
      • By 2002, sickle cell anemia was identified by newborn screening program (MOH, 2006)
      • In January 2005, Congenital Adrenal Hyperplasia has been included as part of the screening (MOH, 2006)
      • Screening for newborns is still not mandatory for each child born in UAE
      • Only the sick babies are being tested due to a lack of awareness of the benefits and high costs
    • 26. Relative Incidence of disease
      • Since the Implementation of the screening program, From Jan 1995
      • until Dec 2005 by MOH: (MOH, 2006)
      • 385,135 infants were screened with the relative incidence of:
      • 1: 1963 for congenital hypothyroidism, 188 prevented from mental retardation
      • 1: 14,812 classic PKU, 26 prevented from mental retardation
      • 0.06% for sickle disease and 0.9% for sickle cell traits
    • 27. Status of Newborn Screening in other GCC countries
      • Aug 2005, National Newborn Screening started in Saudi Arabia, relative incidence of disorder is 1:758 (Study by NLNBS, 2005-2006)
      • Implementation of National screening program including metabolic screening is under consideration in Bahrain
      • Establish a national NBS program by using Tandem Mass Spectrometry is under consideration in Kuwait
      • National newborn screening is yet to be established in Oman
    • 28. Barriers to Newborn Screening
      • Cost of the screening and treatment
      • Test cannot be done at birth (birth has to be in a hospital)
      • Insufficient sampling due to the lack of proper training and education
      • Difficult to reach in different geographic location
      • Problems with recall and follow up cases
    • 29. Way Forward
      • Governments need to take measures to make NBS mandatory for each and every baby born in the region
      • Technical, Financial support and regional collaboration needed
      • Consider Tendem Mass Spectrometry to widen the scope of the program
      • Systematically evaluate all phases of the program including systemic evaluation of program data
    • 30. Conclusion
      • All babies have equal right to live healthy lives
      • &
      • We need to create the platform for them
    • 31. How does MS/MS work?
    • 32. How does MS/MS work?
    • 33. How does MS/MS work?
      • A tandem mass spectrometer is simply 2 mass spectrometers hooked together with a special chamber between the 2 instruments
      • After being prepped, the sample is injected into the first instrument.
      • in the first instrument, the sample is ionized to produce molecular ions and the type of molecules present are determined based upon mass-to-charge ( m / z ) ratio
      • The ionized molecules are sorted and weighed.
      • Afterward, the sample is sent into the collision cell chamber.
      • the molecular ion sample is broken into fragmented pieces, called analytes , in the collision cell chamber
      • After being fragmented, the sample is passed into the second instrument where quantities of the selected analyte(s) are sorted and weighed according to their m / z ratio.
      • The peak of each analyte is compared to internal standard to yield both a qualitative and quantitative result in computer
    • 34. If the child is older and no symptoms, parent still want to test NBS
      • Testing can be done at any age. Although many of the disorders will cause clinical symptoms at an early age, some may not show symptoms for months or years.
      • It is important to screen all siblings, or to perform more specific diagnostic tests of siblings of any babies found to have one of these disorders.
      • If the symptoms are there, this may not offer additional information but this will help them to discuss further with the pediatricians/genetic counselors
    • 35. What happens if baby is a carrier
      • It is important for the parents to know if the baby is a CF carrier or has a hemoglobinopathy trait so they can:
      • tell their child later in life. His or her future partner can choose to have testing to identify the
      • couple’s chances of having a baby with CF, or a clinically significant hemoglobinopathy.
      • If the baby is a CF carrier or has a hemoglobinopathy trait, one parent is almost certainly a carrier. There is a small risk that both parents are carriers which would have implications for future pregnancies.
      • Resources are available to assist in counseling families with regards to these issues.
    • 36. Critical steps for effective Newborn Screening
      • Screening must be done soon after the birth (within 2 weeks)
      • Initial follow-up of an abnormal value and repeat analysis needs to be done
      • Confirmatory testing is required in case of repeated abnormal value
      • Prompt referral of patients with confirmed or suspected disorders
    • 37. Resources for improved NBS program
      • Clinical and biochemical geneticists
      • Pediatric subspecialists
      • Genetic counselors
      • Metabolic dieticians
      • Audiologists/Otolaryngologists
    • 38. Fatty acid oxidation pathway
    • 39. Organic acid disorder
    • 40. Amino acid disorder