Genetics and Newborn Screening

Tandem Mass Spectrometry
Newborn Screening

Information for Physicians and
Other Health Care Providers

What is newborn screening?

Newborn screening involves laboratory testing of all newborn infants for certain genetic/metabolic or endocrine disorders of body chemistry. In addition to laboratory capabilities, necessary components of a successful newborn screening program include tracking and referral of at-risk infants until further diagnostic testing is performed and long-term follow-up of children diagnosed with a disorder.

These tests should be considered screening tests only. Screening can indicate the possibility that an infant may be at risk for a disorder included in the testing panel. Additional diagnostic tests are necessary to determine if the infant with an abnormal test actually has a disorder.

What are the limitations?

Not all affected infants may be identified through screening. The accuracy of screening tests depends on various factors, including the way the specimen is collected, infant’s age at testing, birth weight, gestational age, feeding type, transfusion status, medications and the presence of co-existing illness or medical conditions. If the infant with normal screening test results has symptoms of a disorder or medical problems associated with metabolic disorders, further diagnostic tests may be necessary regardless of the baby’s newborn screening results. While newborn screening has proven to be reliable in the early detection of some metabolic, endocrine and hemoglobin disorders, as with any laboratory tests, false positive and false negative results are possible.

What is tandem mass spectrometry newborn screening?

In addition to providing screening for the six legacy newborn screening disorders (biotinidase deficiency, congenital adrenal hyperplasia, congenital hypothyroidism, galactosemia, phenylketonuria and sickle cell disease and other hemoglobinopathies), on July 1, 2002, the Illinois Department of Public Health (IDPH) Division of Laboratories implemented an additional laboratory technology for screening the dried blood filter paper specimens collected from newborn infants. This technology, tandem mass spectrometry or MS/MS, utilizes special instruments to analyze the dried blood spot specimens for specific metabolites that are produced during the metabolism of proteins and fats. MS/MS screening is utilized to detect amino acid, organic acid and fatty acid oxidation disorders. This technology supplements, rather than replaces existing laboratory technologies.

What analytes are measured by tandem mass spectrometry?

MS/MS detects abnormal levels of amino acids and acylcarnitines. Abnormal elevations of these amino acids may indicate the newborn is at risk for disorders of amino acid metabolism. Free carnitine is a chemical that acts as a transporter of fatty acids into and out of the mitochondria, and is necessary for normal energy metabolism. Acylcarnitines are fatty acids or organic acids that are bound to carnitine. These acylcarnitines vary in size, based on the number of carbon atoms and the type of chemical bonds within the molecule. Abnormal levels of these acylcarnitines can act as markers for certain organic acid and fatty acid oxidation metabolic disorders.

baby feetWhen will I get MS/MS results?

Abnormal MS/MS results are reported to the physician of record as soon as possible by the Genetics/Newborn Screening Program follow-up staff. The most serious abnormal results are reported by phone, letter and fax; and recommendations for further testing or referral to a metabolic specialist also are provided, along with a list of recommended metabolic specialists and a fact sheet about the suspected disorder. A written report of all normal and abnormal test results for each specimen received also will be sent to the submitting hospital by the Illinois Department of Public Health Division of Laboratories.

What metabolic disorders can be detected by tandem mass spectrometry?

MS/MS enables the Illinois Department of Public Health Division of Laboratories to detect several broad categories of metabolic disorders, including amino acid disorders and several urea cycle disorders, organic acid disorders and fatty acid oxidation disorders. The following is a summary of the disorders that may be detected by tandem mass spectrometry during the newborn period.

Amino acid disorders*   Analytes (Amino acids)**
  • Phenylketonuria (PKU) or Hyperphenylalaninemia
  • Phenylalanine
  • Maple syrup urine disease (MSUD)
  • Leucine/Isoleucine, Valine
  • Homocystinuria (cystathionine synthase deficiency) or Hypermethioninemia
  • Methionine
  • Tyrosinemia, type I and possibly type II or type III
  • Tyrosine (elevations may not be detectable on filter paper in first
    days of life)
  • 5-oxoprolinuria (glutathione synthetase deficiency)*
  • 5-oxoproline
Urea cycle disorders*    
  • Citrullinemia
  • Citrulline
  • Argininosuccinic aciduria (ASA)
  • Citrulline, Argininosuccinic acid
  • Argininemia*
  • Arginine
Fatty acid oxidation disorders*   Analytes (Acylcarnitines)**
  • Short chain acyl-CoA dehydrogenase deficiency (SCAD)
  • C4
  • Isobutyryl-CoA dehydrogenase deficiency (IBCD)
  • C4
  • Glutaric aciduria, type 2 (GAII) or Multiple acyl-CoA dehydrogenase deficiency (MADD)
  • C4, C5, C8:1 , C8, C12, C14, C16, C5-DC
  • Medium/Short chain L-3-hydroxyacyl-CoA dehydrogenase deficiency (M/SCHAD)*
  • C4-OH
  • Medium chain acyl-CoA dehydrogenase deficiency (MCAD)
  • C6, C8, C10, C10:1
  • Long chain 3 hydroxyacyl-CoA dehydrogenase def. (LCHAD)
  • C16-OH , C18:1-OH
  • Trifunctional protein deficiency (TFPD)*
  • C16-OH , C18:1-OH
  • Very long chain acyl-CoA dehydrogenase deficiency (VLCAD)
  • C14:1 , C14, C16
  • Carnitine palmitoyl transferase deficiency, type 2 (CPTII)*
  • C16 , C18:1, C18
  • Carnitine palmitoyl transferase deficiency, type 1A (CPT1A)*
  • C0 elevated, low C16, C18
  • Carnitine/acylcarnitine translocase deficiency (CACT)*
  • C16 , C18:1, C18
  • Carnitine uptake defect (CUD)*
  • Low C0 - may not be detected in first few days of life
Organic acid disorders*   Analytes (Acylcarnitines)**
  • Propionic acidemia (PA)*
  • C3
  • Methylmalonic acidemia (MMA)*
  • C3
  • Malonic aciduria (MA)*
  • C3-DC
  • Multiple carboxylase deficiency (MCD)
  • C5-OH
  • 3-hydroxy 3-methylglutaric-CoA lyase deficiency (3HMG)
  • C5-OH
  • 3-methylcrotonyl-CoA carboxylase deficiency (3MCC)
  • C5-OH
  • 3-methylglutaconic aciduria (3MGA)
  • C5-OH
  • 2-methylbutyryl-CoA dehydrogenase deficiency (2MBD)
  • C5
  • Isovaleric acidemia (IVA)
  • C5
  • Glutaric acidemia, type 1 (GAI)
  • C5-DC
  • Beta-ketothiolase deficiency (BKT)*
  • C5:1, C5-OH




Some forms (genotypes) of these disorders may not be detected by neonatal screening, may not be detected in a newborn dried blood spot or are extremely rare (1:>250,000 births).

Primary MS/MS analyte(s) written in bold type.

MS/MS analytes are measured in micromoles per liter (uM/L).

For substituted carnitines, a notation of (Cx) is used, in which (x) denotes the number of carbons in the fatty acid radical.

Hydroxylation is designated by (-OH), dicarboxylic acids are designated by
(-DC), and unsaturation of the fatty acid chain is designated by (:1).

What if I have questions?

Please contact the Genetics/Newborn Screening program at 217-785-8101. The Newborn Screening Practitioner’s Manual is available to health care professionals. For laboratory services, please contact the IDPH Division of Laboratories at 312-793-4752.

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Illinois Department of Public Health
535 West Jefferson Street
Springfield, Illinois 62761
Phone 217-782-4977
Fax 217-782-3987
TTY 800-547-0466
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