Presentation is loading. Please wait.

Presentation is loading. Please wait.

Mass Screening Using Tandem Mass Spectrometry: Friend or Foe? Dawn C. Allain, MS, CGC Childrens Hospital of Wisconsin.

Similar presentations

Presentation on theme: "Mass Screening Using Tandem Mass Spectrometry: Friend or Foe? Dawn C. Allain, MS, CGC Childrens Hospital of Wisconsin."— Presentation transcript:

1 Mass Screening Using Tandem Mass Spectrometry: Friend or Foe? Dawn C. Allain, MS, CGC Childrens Hospital of Wisconsin

2 History of NBS Dr. Centerwall Dr. Guthrie MA and OR implement legislation

3 History of NBS NC begins piloting MS/MS NC and MA begin newborn screening with MS/MS WI begins MS/MS NBS

4 States Screening by MS/MS Maine Massachusetts Minnesota North Carolina Ohio Wisconsin ** as of September 2001 –

5 Why Use MS/MS? Small sample size requirement Fast Screens for many diseases Cost Public awareness and advocacy

6 Mass Spectrometry Ion separation and quantification Produces charged particles Uses electrical and magnetic fields Detection system

7 Sansom, Molecular Medicine Today, March 1999




11 MS/MS Analysis Aminoacidopathies Organic acidurias Fatty acid oxidation disorders

12 Aminoacidopathies l Arginosuccinic Aciduria Citrullinemia Homocystinuria Maple Syrup Urine Disease Phenylketonuria Tyrosinemia

13 Organic Acid Disorders 2,4-Dienoyl-CoA Reductase Deficiency 3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency 3-Ketothiolase Deficiency

14 Organic Acid Disorders 3-Methylcrotonyl-CoA Carboxylase Deficiency 3-Methylglutaconyl-CoA Hydratase Deficiency Glutaric Acidemia Type I

15 Organic Acid Disorders Isovaleric Acidemia Methylmalonic Acidemia Mulitple CoA Carboxylase Deficiency Propionic Acidemia

16 Fatty Acid Oxidation Disorders 3-Hydroxy Long Chain Acyl-CoA Dehydrogenase Deficiency (LCHAD) Carnitine Palmitoyl Transferase Deficiency Type II (CPT II) Long Chain Acyl-CoA Dehydrogenase Deficiency (LCAD) Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCAD)

17 Fatty Acid Oxidation Disorders Multiple Acyl-CoA Dehydrogenase Deficiency (Glutaric Aciduria type II) Short Chain Acyl-CoA Dehydrogenase Deficiency (SCAD) Very Long Chain Acyl-CoA Dehydrogenase Deficiency (VLCAD)

18 Newborn Screening Criteria Criteria Incidence >1/100,000 Significant morbidity/mortality Successful treatment Reasonable cost Technology OA/FAOD/AA 1/5,000 to 1/10,000 Severe medical complications/death Diet & avoid fasting < $10.00 MS/MS

19 False Positives Cut-off levels of acylcarnitines may be too low TPN feedings Prematurity Sampling Error

20 False Negatives Cut-off levels of acylcarnitines may be too high Mild clinical course Sampling Error

21 Follow-up Positive MS/MS NBS Result PMD called and faxed results Consultant names provided Medical management recommended F-up by PMD or Genetic Center

22 Organic Acidemia Follow-Up Initial Follow-Up Urine organic acids Acylcarnitine profile Plasma carnitine Plasma amino acids

23 Additional OA Follow-Up Enzyme analysis in lymphocytes Enzyme analysis in fibroblasts Molecular testing

24 Fatty Acid Oxidation Follow-Up Initial work-up Urine organic acids Urine acylglycines Acylcarnitine Profile Plasma carnitine DNA mutations (MCAD and LCHAD)

25 Other FAOD Work-Up Fibroblast studies Fatty acid oxidation studies Direct enzyme analysis Western blot Test siblings

26 Aminoacidopathy Follow-Up Initial work-up Plasma amino acids Other Laboratory Analysis Orotic acid Ammonia Urine organic acids DNA analysis

27 Wisconsin Experience Pilot testing began May 1999 Analyzed all specimens received Established instrument reliability Developed reporting policies Developed follow-up protocols Routine testing began April 2000 OA and FAO disorders only

28 Wisconsin Experience Organic Acidemia 1 - PA MBCDD 2 - C3/C C3 2 - C5,C5/C3 1 - C5/C2,C5/C3 5 - C5 1 - C3, C5 23 Possible 5 – 3-MCC 2 - MMA 1 - MA 8 - C5OH 5 - C3,C3/C C5,C5/C3,C5/C2 1 - C3DC 1 - C5DC 33Definite

29 3-MCC Case Study Initial NBS result (6/7/01) C5OH = 6.45 (>0.6) Referred to state consultant (6/9/01) Patient seen on 6/12/01 F-up laboratory analysis Results obtained (6/15/01) Sibling tested (6/22/01)

30 3-MCC NBS Issues Prevalence Diagnosis Severity

31 Wisconsin Experience FAOD 1 - SCAD10 - C4 7 - C C6,C8,C C14,C14:1, C14:2 2 - C14,C14:1 1 - C10,C C16,C18,C16:1,C18:1 24 Possible 4 - SCAD 2 - MCAD 1 - GAII 5 - C4,C4/C2,C4/C3 2 - C6,C8,C10:1,C8/C C4,C5,C14,C C14,C14:1,C14:2,C16:1 9Definite

32 SCAD - NBS Issues l Prevalence l Mild presentation l 2 homozygous for G625A polymorphism* *Corydon et al, Ped Res 49 (1):28-23, 2001

33 Wisconsin Experience Aminoacidopathies 3 Tyrosinemia – none confirmed 1 Citrullinemia - confirmed

34 Tyrosinemia Issues Transient tyrosinemia Prematurity False negatives

35 Impact of NBS by MS/MS on Families Anxiety Unknown Limited Resources

36 Impact of NBS by MS/MS on State Laboratories Start-up cost/New technology Programming False negatives and false positives Detection of undefined disorders

37 Impact of NBS by MS/MS on Genetic Clinics Increased clinic load Long-term treatment Improved quality of life Natural history

38 Summary Collaboration Close Follow-up Supportive Counseling

39 Acknowledgements WI Newborn Screening Laboratory Gary Hoffman, PhD Childrens Hospital of Wisconsin William J. Rhead, MD, PhD Waisman Center, UW Jon Wolff, MD, PhD Kristine Hanson, MS, CGC

Download ppt "Mass Screening Using Tandem Mass Spectrometry: Friend or Foe? Dawn C. Allain, MS, CGC Childrens Hospital of Wisconsin."

Similar presentations

Ads by Google