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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

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  • 1. Dr. Sanjida Ahmed (Director: Research) Eastern Biotech & Life Sciences DuBiotech Park, Dubai UAE Phone: 00971 4 3692061 Email: [email_address] www.easternbiotech.com 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 (Kidshealth.org)
    • 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.
    • (Kidshealth.org)
    • 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. (Kidshealth.org)
  • 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