Expanded Newborn Screening


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

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