Newborn Screening for Genetic and Metabolic Disorders

Congenital Conditions Recommended for Routine Screening

Newborn screening is important for the early detection of inherited genetic and metabolic disorders, allowing doctors to preemptively treat or manage affected babies to reduce illness, disability, or death. The screening is performed soon after birth and involves a simple blood test alongside a non-invasive hearing test.

Currently, in the United States, there are 35 genetic and metabolic disorders for which screening is recommended and 26 secondary disorders for which screening may be performed. The list of newborn screening tests can vary by state, with most performing at least 30.

Collecting Blood For Newborn Screening Test
Scientifica / Creative RM / Getty Images

History

The concept of newborn screening began in the 1960s with the development of a genetic screening test for phenylketonuria, a metabolic birth defect. The innovative method and collecting and transporting blood samples on filter paper made wide-scale screening not only viable but cost-effective.

Since then, many more blood-based screening tests have been developed, including newer tandem mass spectrometry (MS/MS) technologies that can screen for multiple disorders using only a few drops of dried blood.

Unlike traditional blood tests that need to be evaluated individually, MS/MS can detect a broad range of congenital anomalies using a device called a mass spectrometer, which identifies enzymes and proteins based on patterns of refracted light. By comparing the results with a reference range of expected values, lab technicians can confirm with a high level of accuracy whether a genetic or metabolic disorder is present, usually within two or three minutes.

In addition to blood-based tests, hearing is routinely screened to detect newborn hearing loss. The hearing tests are non-invasive and only take a few minutes to perform.

Today, over 98% of the four million newborns born annually in the United States are tested for more than 30 treatable genetic, metabolic, endocrine, and infectious diseases within the first week of life.

Newborn Screening Laws

The Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) issues regular advisements known as the Recommended Universal Screening Panel (RUSP) which lists the core conditions for which newborn screening is highly recommended and secondary conditions for which screening is optional.

While all 50 states and the District of Columbia offer newborn screening, there is no federal law governing such screenings. Because of this, states can opt to change the panel of disorders listed in the RUSP and/or shift the responsibility for testing from the state to the individual doctor or facility. This can lead to a significant lack of equity in some states.

As of 2017, 49 states and the District of Columbia screen for 30 or more of the core conditions recommended by the ACHDNC. Other states like California screen for more than the core 34 and, by doing so, significantly reduce their annual health care costs.

The funding of screening programs continues to challenge many state legislatures. To overcome this, a bill called the Newborn Screening Saves Lives Reauthorization Act was introduced in the U.S. House of Representatives in May 2019 to improve and expand current newborn screening initiatives throughout the United States.

Core and Secondary Screening

As of July 2018, there are 35 core conditions that the ACHDNC recommends be included in routine screenings and 24 secondary conditions that should be considered based on the availability of effective treatments.

Core Conditions
  • Propionic acidemia

  • Methylmalonic acidemia (methylmalonyl-CoA mutase)

  • Methylmalonic acidemia (cobalamin disorders)

  • Isovaleric acidemia

  • 3-methylcrotonyl-CoA carboxylase deficiency

  • 3-hydroxy-3-methylglutaric aciduria

  • Holocarboxylase synthase deficiency

  • Beta-ketothiolase deficiency

  • Glutaric acidemia type I

  • Carnitine uptake/transport defect

  • Medium-chain acyl-CoA dehydrogenase deficiency

  • Very long-chain acyl-CoA dehydrogenase deficiency

  • Long-chain L-3 hydroxyacyl-CoA dehydrogenase deficiency

  • Trifunctional protein deficiency

  • Argininosuccinic aciduria

  • Citrullinemia, type I

  • Maple syrup urine disease

  • Homocystinuria

  • Phenylketonuria

  • Tyrosinemia, type I

  • Primary congenital hypothyroidism

  • Congenital adrenal hyperplasia

  • Sickle cell anemia (SS disease)

  • Sickle beta-thalassemia

  • Sickle cell disease (SC disease)

  • Biotinidase deficiency

  • Critical congenital heart disease

  • Cystic fibrosis

  • Galactosemia

  • Glycogen storage disease type II

  • Congenital hearing loss

  • Severe combined Immunodeficiencies

  • Mucopolysaccharidosis type 1

  • X-linked adrenoleukodystrophy

  • Spinal muscular atrophy due to homozygous deletion


Secondary Conditions
  • Methylmalonic acidemia with homocystinuria

  • Malonic acidemia

  • Isobutyrylglycinuria

  • 2-Methylbutyrylglycinuria

  • 3-Methylglutaconic aciduria

  • 2-Methyl-3-hydroxybutyric aciduria

  • Short-chain acyl-CoA dehydrogenase deficiency

  • Medium/short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency

  • Glutaric acidemia type II

  • Medium-chain ketoacyl-CoA thiolase deficiency

  • 2,4 Dienoyl-CoA reductase deficiency

  • Carnitine palmitoyltransferase type I deficiency

  • Carnitine palmitoyltransferase type II deficiency

  • Carnitine acylcarnitine translocase deficiency

  • Argininemia

  • Citrullinemia, type II

  • Hypermethioninemia

  • Benign hyperphenylalaninemia

  • Biopterin defect in cofactor biosynthesis

  • Biopterin defect in cofactor regeneration

  • Tyrosinemia type II

  • Tyrosinemia type III

  • Various other hemoglobinopathies

  • Galactoepimerase deficiency

  • Galactokinase deficiency

  • T-cell related lymphocyte deficiencies

How Screening Is Done

The process of newborn screening is relatively quick and easy. Between 24 hours to seven days after birth, a few drops of blood are taken from an infant’s heel and placed on a special card. The paper is sent to a specialized laboratory for testing.

The results of the blood tests are sent to the infant's pediatrician within two to seven days. If any of the tests come back positive, further testing will be done to confirm the diagnosis. Parents do not have to request the tests; they should be automatically performed.

In addition to blood-based tests, a hearing test will be performed to check for hearing loss. It is a non-invasive test that only takes around five to 10 minutes to complete.

There are two standard methods of detecting hearing loss in newborns:

  • Otoacoustic Emissions (OAE): A miniature earphone and microphone can confirm hearing if sounds are reflected back from the ear canal.
  • Auditory Brain Stem Response (ABR): Electrodes placed on the newborn's head can detect the presence or absence of brain’s response to sounds.

A Word From Verywell

With many congenital disorders, the symptoms won't become apparent until days or weeks after the child is born. By identifying these conditions early, treatment can be delivered to prevent harm to the heart, lungs, kidneys, nervous system, or any other affected organ. 

If you have a family history of a congenital disorder, let your OB/GYN know so that tests may be ordered if they are not already included in the mandated screening.

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