Mountain States Genetics Regional Collaborative Center Laboratory - - PowerPoint PPT Presentation

Mountain States Genetics Regional Collaborative Center

Laboratory Quality Assurance Exchange of blood spots for educational purposes to improve quality of newborn screening by MS/MS. PI: Marzia Pasquali, PhD, FACMG University of Utah

18 May 2007

Background

• Newborn screening by tandem mass

spectrometry (MS/MS) has now been implemented in most states.

• Challenges with MS/MS cut-offs and

interpretation of results have been addressed by the Region 4 Laboratory Quality Improvement activity.

• There is still some unresolved issues on how

to deal with borderline/abnormal values reflecting iatrogenic effects.

Goal of the project

• Improve recognition of abnormal

patterns

• Decrease the number of unnecessary

confirmatory tests

• Promote the use of 2nd tier tests
• Decrease the number of false positives

(and false negatives in some cases)

Methods

• The goal will be achieved by:

– Encouraging all the states within Region 6 to participate in Region 4 activity and attend the training sessions – Sending educational challenges (blood spots from real patients with metabolic disorders or with clinical conditions resulting in abnormal amino acids or acylcarnitines) – Compiling a complete report that will address not just the analytical part of testing, but also the follow up/clinical aspect

Existing programs

• CDC proficiency testing

– Quantitative assessment of several analytes, including amino acids and acylcarnitines

• ERNDIM

– Qualitative assessment of blood spots,

• ften from adults or patients on therapy

Newborn screening is a program

Diseases to include in the educational challenges

• Metabolic disorders detected by MS/MS
• Endocrine disorders (CAH) when either the

primary screen or a 2nd tier test is performed by MS/MS

• Hyperalimentation, antibiotics, special diets,

medications

• Other disorders can also be included

Educational challenges

• Markers used
• 2nd tier tests used (if

applicable)

• Significance
• Recommendations for

follow-up

– Confirmatory tests – Metabolic referral – Urgency

• Involvement of

Technical Supervisor/Medical Director/Metabolic consultant

NBS Laboratory NBS Laboratory NBS Laboratory NBS Laboratory NBS Laboratory “Review” Panel

Evaluation Forms

• Clinical description of the patient
• Abnormal metabolites present in the

sample

• Explanation of these abnormalities
• If applicable, the importance of 2nd tier

tests

• Recommendations for follow-up
• Lessons learned from different cases

Example Congenital Adrenal Hyperplasia (receiving corticosteroids)

• Low Birth Weight (g 2,210) with severe

respiratory distress initiated on corticosteroids before collection of newborn screening sample.

• MS/MS test results:

– 17-hydroxyprogesterone: 7.3 ng/mL (Normal) – androstenedione: 4 ng/mL (Normal) – cortisol: 1.7 ng/mL (LOW) – (17-OHP + androstenedione)/cortisol = 6.7 (Abnormal)

Steroid profile by UPLC-MS/MS

03-May-200719:33:46F1220124200740 Q_Premier VAB574 363A207 03-May-2007, 19:33:46

Time 1.00 1.10 1.20 1.30 1.40 1.50 1.60 1.70 1.80 1.90 2.00 2.10 2.20 2.30 2.40 2.50 2.60 2.70 2.80 2.90 % 100 1.00 1.10 1.20 1.30 1.40 1.50 1.60 1.70 1.80 1.90 2.00 2.10 2.20 2.30 2.40 2.50 2.60 2.70 2.80 2.90 % 100 1.00 1.10 1.20 1.30 1.40 1.50 1.60 1.70 1.80 1.90 2.00 2.10 2.20 2.30 2.40 2.50 2.60 2.70 2.80 2.90 % 100 05_03_07_17 3: MRM of 3 Channels ES+ TIC 4.11e4

2.37 2.21 2.09 2.78 2.60 2.54 2.69

05_03_07_17 2: MRM of 3 Channels ES+ TIC 6.55e4

2.00 2.11

05_03_07_17 1: MRM of 3 Channels ES+ TIC 2.15e4

1.29 1.01 1.10

17-hydroxyprogesterone RT = 2.39 min androstenedione RT = 2.00 min cortisol RT = 1.29 min Waters Premiere/Acquity

Distribution of information

• The evaluation forms will be distributed by

electronic mail

• One meeting/year will be organized to

discuss the educational challenges

• Results will also be discussed at the regional

meetings

• Tracking of the performance over time will

determine the impact of the training sessions and the educational challenges

Challenges

• Obtaining blood from patients

– Need for participation of many centers in

• rder to increase the number of cases

– Need for participation of NICUs to identify factors affecting NBS results – Need for consent forms that can be shared by other states

Challenges

• Consent forms

– We will develop general consent forms and we will assist with IRB submission

• Tracking of data

– Develop a database containing information about participating laboratories – Metrics to objectively evaluate results and compare them over time will be developed

Region 6

Arizona MS/MS Colorado MS/MS Montana

(No uniform panel)

Nevada New Mexico Texas MS/MS Utah MS/MS (ARUP) Wyoming Oregon MS/MS Wisconsin MS/MS

Enrollment

• Although this project will start as a

regional effort, enrollment will be open to every laboratory performing NBS by MS/MS

• There will be no cost for laboratories to

participate

Requirements

• Participating laboratories will be asked

to:

– Analyze 2-3 sets of blood spots twice per year – Fill the results form – E-mail the results – Attend one meeting/year

Summary

• This project will:

– Improve the quality of screening – Increase awareness and education about metabolic disorders – Complement the activities of Region 4 collaborative project and the existing proficiency testing run by the CDC