Wisconsin Newborn Screening Laboratory

March 2000 Newsletter: No. 44 Expansion of Newborn Screening

This newsletter is to announce that on April 3rd, 2000, the newborn screening laboratory will begin reporting results for 14 Fatty Acid Oxidation and Organic Acidemia disorders. This will bring the number of disorders screened for in Wisconsin to 21. Topics included in this newsletter are: a brief description of Fatty Acid Oxidation and Organic Acidemia disorders, how this group of disorders meet the Wisconsin criteria for screening, the technology used to detect these disorders, and the reporting scheme.

Fatty Acid Oxidation and Organic Acidemia Disorders

Fatty Acid Oxidation Disorders (FOD) are a class of inborn errors of matabolism where there is an enzyme defect in the fatty acid metabolic pathway which inhibits the body's ability to utilize stored fat. Clinical symptoms of FOD inclue hypotonia, lethargy, and vomiting; the hypoglycemia can lead to coma, encephalopathy, hepatic failure, or death. The following table lists those FOD that will be detected and reported.

Effective treatment for the FOD includes instituting a low-fat diet and supplementing the diet with the prescription drug carnitine. Acute episodes are managed by administering intravenous glucose.

Organic acidurias (OA) are a group of inherited metabolic disorders that lead to accumulation of organic acids in biological fluids (i.e. blood and urine). This, in turn, produces disturbances in the acid-base balance and causes alterations in pathways of intermediary metabolism. These disorders can cause intoxication-like symptoms such as episodes of vomiting, metabolic acidosis, ketosis, dehydration or coma. Some patients may have hypoglycemia, lactic acidosis or hyperammonemia. Chronic symptoms include recurrent vomiting, failure to thrive, hyptonia and global development delay. The following table lists those OA disorders that will be reported.

Symptoms can be diminished by restricing protein in the diet, and in some cases, supplementing with vitamins and/or carnitine.

In 1996, the Newborn Screening Program began considering a recommendation to add the 14 FOD and OA disorders listed above to the newborn screen panel. An extensive review by the Newborn Screening Advisory Group determined that, as a group, these FOD and OA disorders met Wisconsin's established criteria for screening purposes.

Detection of these 14 FOD and OA disorders can be accomplished by measuring levels of acylcarnitines in the blood spot specimens. There are 32 acylcarnitines that are detected and quantified by the tandem mass spectometer using 1/8" disk punched from one of the five blood spots currently submitted for routine newborn screening. No additional blood will be required. Abnormal acylcarnitines result from the reaction of free carnitine in the blood with toxic acyl-CoA esters that are fromed by the underlying block in the enzymatic pathway. Each FOD and OA has a unique abnormal acylcarnitine profile determined by the accumation of specific "acyl groups" as the following diagram illustrates.

For example the abnormal acylcarnitine profile for MCAD is: Hexanoylcarnitine (C6); Octanoylcarnitine (C8); and Decenolycarnitine (C10:1).

In the Spring of 1999, the Newborn Screening Laboratory at the Wisconsin State Laboratoy of Hygiene acquired a tandem mass-spectrometer and in May began pilot testing for the FOD and OA disorders. The goal of this pilot testing was (1) to evaluate the long term instrument performace, (2) collect acylcarnitine data to establish normal reporting levels, (3) develop a reporting and physician support system, (4) gather information regarding the prevalence of these disorders in the Wiconsin population. During the pilot phase abnormal acylcarnitine profiles were reported to a metabolic specialist (Dr. Jon Wolff) who in turn contacted the baby's physician for follow-up testing. Normal results were not reported during the pilot phase. During the pilot phase 45,000 babies were screened. The number of abnormals reported and confirmed is summarized below.

*Initial sample was normal but a second sample was submitted because of a family history of PA. The second sample was abnormal. The case represents a mild form of PA.

All of the children with confirmed diagnoses are healthy and have had no metabolic crises to date. Additionally, we are not aware of any false negative screens during the pilot testing.

The newborn screening laboratory will begin routine reporting of FOD and OA disorders April 3, 2000. Specimens with normal FOD and OA results (i.e. normal acylcarnitine levels) will be listed on the current normal newborn screening report as Fatty Oxidation Disorders and Organic Acidemias. There will be two categories of abnormal acylcarnitine results: Definite Abnormal and Possible Abnormal. The Definite Abnormal category will be those acylcarnitine results that are highly indicative of a particular FOA or AO disorder. Such results will be reported directly to the baby's physician by telephone along with the recommendations as to proper follow up, i.e. obtain confirmatory testing. The laboratory will provide the name of a readily accessible volunteer metabolic specialist that can provide assistance with confirmation, treatment and management of the child should the physician of record want to seek a consulation. The phone call from the State Laboratory will be followed by a standard written abnormal laboratory report on gold paper sent to the physician and the specimen collection site, most often the hospital of birth. As with other definite abnormal newborn screening reports it will provide details on the particular disorder, an interpretation of the test findings, including the levels of the abnormal acylcarnitines(s), and a recommended cours of action for follow-up. The Possible Abnormal category will be used for abnormal acylcarnitine(s) that may not fit a typical FOD or OA profile. These test results will be reported by a written report (blue) to the physician and specimen collection site. Most often the recommendation will be to collect another newborn screening specimen and repeat the testing through the newborn screening laboratory. Examples of a Normal, Definite Abnormal, and Possible Abnormal reports are attached to this newsletter.

The State of Wisconsin is fortunate to have several excellent State-supported metabolic centers with resources to confirm diagnosis and properly treat children with Fatty Acid Oxidation or Organic Acidemia disorders. At each metabolic center (Madison, Milwaukee and Marshfield) a team of medical experts is available to offer families medial, nutritional, and genetic counseling services. many of these services, including any necessary specialized medical formulas, are supported by a congenital disorders grant from the Maternal Child and Health Unit of the Wisconsin Division of Public Health.

The addition of Fatty Acid Oxidation and Organic Acidemia disorders to newborn screening in Wisconsin is another example of public health programs working to improve the health and well-being of Wisconsin citizens. The success, as always, depends upon the excellent working relationship of all the partners involved: the Department of Health and Family Services, State Laboratory of Hygiene, local public health officials, volunteer medical specialists, primary health care providers, and the families. Being on eof the first states in this country to add FOD and OA screening to its newborn screening panel demonstrates our continued leadership in newborn screening into the new millennium.

The Wisconsin Newborn Screening Program is especially fortunate to have available the resources of the Newborn Screening Advisory Metabolic Subcommittee. This panel was instrumental in the entire process of expanding the testing to include FOD and OA disorders to the program. Their involvement began with preliminary consideration of adding these disorders and continued through the pilot phase data evaluation to creating the reporting and follow-up processes described above. The volunteer member are Jon Wolff, M.D.; Sharon Maby, M.D.; Mark Lubinsky, M.D.; Dvid Tick, M.D.; Steven Werlin, M.D.; Michelle Hardy (parent); Darwin and Cheryl Evans (parents); Elizabeth Suckow, R.D.; Glady Kubitz, M.A. R.D.; Linda Stevens R.D.; Sandra VanCalcar, R.D, M.S; Ronald Leassig, Ph.D.; Gary Hoffman; Kris Hanson (consultant); Tim Lockie (consultant); Amy Favour (staff); and Jill Ciske (staff). Richar Aronson, M.D. MPH, charis the Newborn Screening Advisory Group.

Sincerely,