# Presentation: 373532

## The Newborn Screening Quality Assurance Program 

## W. Harry Hannon, Ph.D.

**Chief, Newborn Screening Branch**
**Centers for Disease Control and Prevention **

## Quality Assurance Services provided by NSQAP:

** ****Proficiency testing (PT) panels and evaluations **
**Training, consultations, network resources  **
** ****Technical help  **
** ****Follow-up by a CDC lab scientist for false-negative reports**
** ****Additional dried blood spot specimens can be provided**
**     ****for repeats**
-  **Filter paper evaluations for pre-distribution certification**
** ****Reference materials**** **
** ****Start-up materials: blood spot reference materials,             archived QC materials, and previously distributed PT  specimens**

**Quality Assurance Services provided by NSQAP:**

## MMWR Morbidity and Mortality Weekly Report

**MMWR Morbidity and Mortality Weekly Report**
**April 13, 2001/Vol. 50/No. RR-3**

## DISORDER OF AMINO ACID METABOLISM

- Phenylketonuria				**Phe**
- Maple syrup urine disease		**Leu/Ile, Val**
- Homocystinuria				**Met**
- Hypermethioninemia			**Met**
- Citrullinemia				**Cit**
- Argininosuccinic aciduria		**Cit**
- Tyrosinemia				**Tyr**

## DISORDERS OF FATTY ACID METABOLISM

- Medium-chain acyl-CoA dehydrogenase deficiency		**C8, C6, C10, **C10:1,** **
- Very-long-chain acyl-CoA dehydrogenase deficiency	C14:1,** C14, C16**
- Short-chain acyl-CoA dehydrogenase deficiency		**C4**
- Multiple acyl-CoA dehydrogenase deficiency	**C4, C5, **C8:1,** C8, C12, C14, C16, C5DC**
- Carnitine palmitoyl transferase deficiency		**C16, **C18:1,** C18**
- Carnitine/acylcarnitine translocase defect		**C16, **C18:1,** C18**
- Long-chain hydroxy acyl-CoA dehydrogenase deficiency	C16OH, C18:1OH, C18OH
- Trifunctional protein deficiency			                C16OH, C18:1OH, C18OH

## DISORDERS OF ORGANIC ACID METABOLISM

- Glutaric acidemia Type 1				**C5DC**
- Propionic acidemia					**C3**
- Methylmalonic acidemia					**C3**
- Isovaleric acidemia					**C5**
- 3-hydroxy-3-methylglutaryl CoA lyase deficiency		C5OH
- 3-methylcrotonyl-CoA carboxylase deficiency		C5OH

## Amino Acid Reference MaterialsforPhe, Leu, Met, Tyr, and Valdescribed inClinical Chemistry 1999;45:1269-1277 

## Amino Acid Reference Materials (AARMS) for Start-Up

**n=12**

##  BLOOD MATRIX:  each set made from a single multi-donor batch of pooled red cells and clarified serum; hematocrit adjusted to 55%+1%; frozen before use to hemolyze red blood cells.

**SET DESCRIPTION:  each set contains a non-enriched pool for measurement of endogenous levels and three pools enriched with low, medium, and high levels of amino acids or acylcarnitines.**
** ****AMINO ACID ENRICHMENTS:  each set enriched with  Phe, Leu, Met, Tyr, Val, and Cit.**
**ACYLCARNITNE ENRICHMENTS:  each set enriched with C2, C3, C4, C5, C5DC, C6, C8, C10, C14, and C16.**

**DRIED BLOOD SPOT QUALITY CONTROL MATERIALS**

## ENRICHMENTS OF ACYLCARNITINES

-  QUALITY CONTROL MATERIALS

- (mol/L whole blood)

- Analyte

- Lot 365

- Lot 366

- Lot 367

- Lot 368

- C2

- 0

- 5

- 10

- 20

- C3

- 0

- 3

- 7.5

- 12

- C4

- 0

- 1

- 2.5

- 5

- C5

- 0

- 0.5

- 1.5

- 3

- C5DC

- 0

- --

- --

- --

- C6

- 0

- 0.5

- 1

- 2.5

- C8

- 0

- 0.5

- 1

- 2.5

- C10

- 0

- 0.25

- 0.75

- 1.5

- C14

- 0

- 0.5

- 1.5

- 3.0

- C16

- 0

- 4

- 8

- 12

## A Model CLIA Certified

**•** 	Must be at least 3 testing events at equal intervals during the year - ***NSQAP has 4 events per year, one per quarter***.
**•** 	Specimens must simulate the unknown test sample - ***NSQAP  specimen matrix:  whole blood adjusted to a newborn hematocrit*****. **
**•** 	Specimens must cover the clinically relevant range of values or clinical significance - ***NSQAP enriches specimens with analyte concentrations that are typical of  real disease states***.
**•** 	Specimens may be distributed by Federal Express or mail - ***NSQAP sends all packages by FedEx with tracking.***
**•** 	Assess the accuracy of the laboratory’s response (grading) in accordance with specified criteria – ***NSQAP provides instructions with codes for the assessment grading******. ***
-       42 Code of Federal Regulations (CFR),  430.0, October 2000

**A Model CLIA Certified**
**Proficiency Testing Program**

## PROFICIENCY TESTING (PT)

**Participation usually a regulatory requirement for labs that report patient specimen results**
**Provides an external measure of the total system**
**Uses blind-coded samples: normal and disorder/range**
**Evaluates performance of the moment only/snapshot**
**Meets requirements for certification **

## Means and Ranges of Acylcarnitine Cutoff Values

**Reported by Domestic MS/MS Laboratories**

** ****Mean Cutoff**
******mol/L blood**

- Source: Quarter 3, 2003 NSQAP Data

**C3**
**C4**
**C5**
**C6**
**C8**
**C10**
**C14**
**C16**
**C5DC**

**7.10**
**1.57**
**0.86**
**0.59**
**0.52**
**0.55**
**0.88**
**9.53**
**0.35**

- 15
- 15
- 15
- 15
- 16
- 14
- 14
- 15
- 14

**N**

- 3.30-10.00
- 0.80-2.40
- 0.35-1.62
- 0.17-2.50
- 0.19-1.00
- 0.25-0.90
- 0.26-2.21
- 2.20-14.00
- 0.10-1.70

- Represents a wide spread of reported cutoff values

- N = Number of laboratories reporting their cutoff values

- Min/Max

## Distribution of Propionylcarnitine (C3) Cutoff Values 

**among Participating Laboratories**

- Source: Quarter 3, 2003 NSQAP MS/MS  Data

## Amino Acid Mean Cutoff Values

**Reported by MS/MS Laboratories **

**Min/Max**
**mg/dL**

**17**

**15**

**18**

**16**

**16**

**2.4**

**4.1**

**1. 2**

**6.3**

**3.8**

**1.7- 3.3**

**2.8- 5. 2**

**0.8-1.9**

** ****2.2- 9.1  **

**2.9- 5.8**

**Mean Cutoff**
**Value**
**mg/dL blood**

**1.6**

**16**

**0.6-4.4**

**Phenylalanine**

**Leucine**

**Methionine**

**Tyrosine**

**Valine**

**Citrulline**

**N**

- Source: Quarter 3, 2003 NSQAP MS/MS  Data

## Distribution of Tyrosine Cutoff Values amongParticipating Laboratories

- Source: Quarter 3, 2003 NSQAP MS/MS  Data

## How Can Labs Use NSQAP for MS/MS Start-up?

- Enroll in NSQAP PT program as soon as MS/MS instrument start-up begins.
- Request previous quarter’s PT specimens and report.
- Request supplies of archived QC materials for instrument comparison and performance monitoring.
- Request Reference Materials for method calibration and assessments of method linearity.
- View the 2003 MS/MS annual report online at
- 	*http://www.cdc.gov/nceh/dls/newborn_screening.htm*.
-       Contact  Connie Singleton at 770-488-4582 or
-       email at csingleton1@cdc.gov for enrollment and
-       to request materials.