STATEMENT OF BASIS AND PURPOSE AND SPECIFIC
STATUTORY AUTHORITY FOR

Amendments to Newborn Screening Regulations, 5 CCR 1005-4, Section 1.6, List of Conditions for Newborn Screening (First Screening)

Adopted by the State Board of Health on

November 28, 2007

Basis and Purpose: Under Section 2541004(1)(b), C.R.S., the Board of Health has the authority to change Newborn Screening regulations regarding the disorders for the first screen. The Executive Director is vested with the authority to make changes in the second screen Section 2541004.5(1)(b), C.R.S.

Prior to the amendment, the newborn screening regulations provided that babies born in Colorado would be screened for the following disorders:

1.6.1.1Phenylketonuria

1.6.1.2Congenital Hypothyroidism

1.6.1.3Hemoglobinopathies

1.6.1.4Galactosemia

1.6.1.5Cystic Fibrosis

1.6.1.6Biotinidase Deficiency

1.6.1.7Congenital Adrenal Hyperplasia

1.6.1.8Medium Chain Acyl-CoA dehydrogenase deficiency

1.6.1.9Very Long Chain Acyl-CoA dehydrogenase deficiency

1.6.1.10 Long-chain Acyl CoA dehydrogenase deficiency

1.6.1.11Trifunctional protein deficiency

1.6.1.12Carnitine Acyl-carnitine translocase deficiency

1.6.1.13Short Chain Acyl-CoA dehydrogenase deficiency

1.6.1.14Carnitine palmitoyltransferase II deficiency

1.6.1.15Glutaric acidemia Type 2

1.6.1.16Arginosuccinic acidemia

1.6.1.17Citrullinemia

1.6.1.18Tyrosinemia

1.6.1.19Hypermethionemia

1.6.1.20Maple Syrup urine disease

1.6.1.21Homocystinuria

1.6.1.22Isovaleric acidemia

1.6.1.23Glutaric acidemia Type 1

1.6.1.243-hydroxy-3 methyl glutaric aciduria

1.6.1.25Multiple Carboxylase deficiency

1.6.1.263-methylcrotonyl-CoA carboxylase deficiency

1.6.1.273-methylglutaconic aciduria

1.6.1.28Methylmalonic acidemias

1.6.1.29Propionic academia

1.6.1.30beta-Ketothiolase deficiency

In the past year the Newborn Screening Advisory Committee and an appointed subcommittee on metabolic disorders detectable by MS-MS have reviewed screening findings including the 21 cases of metabolic disease detected in Colorado newborns and an additional four cases of metabolic disease among the babies screened for Wyoming and other private contractees and have concluded that four additional disorders warrant inclusion in the first screen disorder list. Attachment 1.Citing the recommendation of the American College of Medical Genetics (ACMG) the Newborn Screening Advisory Committee recommends that the Colorado Newborn Screening Program add the following additional disorders:

  • Carnitine Uptake Defect (CUD)
  • Arginase Deficiency (ARG)
  • Malonic Acidemia (MAL)
  • Carnitine Palmitoyltransferase deficiency 1A (CPT1A)

Further the Newborn Screening Advisory Committee recommends that the terminology for two previously approved disorders be revised to achieve concordance with publications1 that the names of one previously approved disorder be revised as listed:

Current terms of disorders

1.6.1.10Long-chain Acyl CoA dehydrogenase deficiency

1.6.1.243-Hydroxy-3-Methyl glutaric aciduria

New terms for disorders:

1.6.1.10 Long-chain L-3-Hydroxy Acyl CoA dehydrogenase deficiency

1.6.1.243-Hydroxy-3-Methylglutaryl-CoA lyase deficiency

The Colorado Newborn Screening statute specifies the criteria for the inclusion of disorders for newborn screening. These criteria are listed below:

  1. Condition for which the test is designed presents a significant danger to the health of the infant or his family

Carnitine Uptake Defect (CUD). Metabolic decompensation with cardiomyopathy; some cardiomyopathy develops later.
Arginase Deficiency (ARG) progressive spastic quadriplegia and mental retardation; hyperammonemic episodes occasionally.
Malonic Acidemia (MAL) mortality and long term disability
Carnitine Palmitoyltransferase deficiency 1A (CPT1A) hypoketotic hypoglycemia, convulsions, coma, renal tuberalr acidosis, and Reye-like episodes.
  1. Condition is amenable to treatment.

Carnitine Uptake Defect (CUD). Treatment is carnitine supplementation which has been show to prevent episodes of metabolic decompensation, but long term outcome data is lacking.
Arginase Deficiency (ARG) Protein-restricted diet , sodium benzoate or phenylbutyrate treatment can be expected to to reduce neorologic dysfunction associated witht eh deficiency.
Malonic Acidemia (MAL) Carnitine supplementation and dietary management
Carnitine Palmitoyltransferase deficiency 1A (CPT1A) Fasting avoidance, medium chain triglycerides (MCT) oil supplementation have been shown to mitigate episodes of hypoketotic hypoglycemia and associated complications.

3. Incidence of the condition is sufficiently high to warrant screening.

The incidence of disorders detectable by MS/MS is higher than any other disorder for which newborn screening is currently applied.

Table 1*

Carnitine Uptake Defect ( CUD) / <100,000
Argininemia (Arginase Deficiency,ARG) / <100,000
Malonic Acidemia (MAL) / <100,000
Carnitine Palmitoyltransferase deficiency 1A (CPT1A) / <100,000

*incidence rates are estimates as the number of cases reported in the literature are too low to make accurate estimates, source: ACMG report

4. The test to detect the condition meets commonly accepted standards of reliability

MS/MS has become the standard of care. Forty states are either currently using MS/MS to screen for disorders or plan to introduce the method shortly. Most either conduct the analytical screening in their state laboratories, or another state laboratory (IA serves SD). Some state programs use a state laboratory with regional screening services [examples MA and OR] or use commercial laboratory services.

5. Cost-benefit consequences of screening are acceptable.

The only detailed cost analysis is that for MCAD from the United Kingdom where an assessment was completed and published in 1997. The authors examined cost-per-year of life saved. They point out that their model only included the cost to avert mortality and did not include measures of other outcomes (e.g. averting neurologic injury). They concluded that their results conservatively estimated the total benefits.

The costs included in the model were the costs of screening, costs of treatment and effectiveness of treatment. For MCAD, the estimated treatment cost per life-year saved is approximately $50. Leaving aside other benefits of screening not included in their model, this estimate indicates that screening for MCAD is highly cost effective as a tool to improve health for a population. A cost-benefit analysis has also recently been conducted, showing a cost per quality-adjusted life year saved by MS/MS ranging from $736 to $11,419 depending on the number of false positive tests assumed (Schoen et al Pediatrics 2002; 110:781-6.).

Laboratory tests and follow-up: the current NBS fee of $65 cover all costs associated with laboratory screening and followup.

Implementation for the disorders listed will take place on or about July 1, 2006.

List of the disorders to be added to the Newborn Screening Laboratory testing

1.6.1.31Carnitine Uptake Defect

1.6.1.32Arginase Deficiency

1.6.1.33Malonic acidemia

1.6.1.34Carnitine pamitoyltransferase 1A deficiency

Specific Statutory Authority: Under the authority contained in Sections 25-4-801 through 254-804 and 25-4-1001 through 25-4-1006 (not including Section 25-4-1004.7) C.R.S. (1998), the Newborn Screening Regulations are established.

Alternative Rules Considered and Why Rejected: As the field of newborn screening as universally adopted the MS-MS technology for detection of the disorders at issue, no alternative rule are deemed appropriate.

Major Factual and Policy Issues Encountered: None

1. Sweetman, L., Millington, D.S., Therrell, B.L. et al. Naming and Counting Disorders (Conditions) Included in Newborn Screening Panels. Pediatrics, 117:308-314, 2006.

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Source: J.L. Beebe PhD 7/16/07