Newborn Screening

Starting on the right foot with Newborn Screening

Programs that screen newborn babies for selected genetic and metabolic diseases are vital to the health of infants. Without these screenings, babies would be at risk for developing severe illnesses that could cause brain damage or death. With early detection and treatment, however, many of these diseases can be managed successfully. Newborn screenings are thus an important part of providing comprehensive care for all infants.

How it works

Newborn screening tests for any disorders involving the metabolism of nutrients in the body. These disorders can lead to abnormalities in body chemistry, which can cause various diseases or disorders. Most metabolic disorders are caused by a lack of a particular enzyme, which in turn prevents the body from breaking down a certain nutrient. This can then lead to problems with the body’s ability to derive the benefit of this nutrient, which can result in a disease or disorder of body chemistry.

As most affected children show no sign of the disease at birth, the tests have to be done within 24 – 72 hours of birth. Newborn screening tests are therefore designed to pick up these diseases and disorders before any harmful effects set in,

The screening process

FAQ

Should all newborns be screened?

These diseases are rare. However, since we do not know which child may be at risk of a metabolic disease, international practice recommends that all children undergo newborn screening.

By testing all children, we are assured of finding the few that are affected, for whom early detection and treatment of disease is vital.

When should newborns be screened?

The ideal time is between 24 and 72 hours after the birth but up to a week after birth is still acceptable. The baby needs to have had a few feeds and started the digestion and metabolism of proteins, carbohydrates, and fats (all found in breast milk and formula milk to bring the disorder to light.) Tests done outside the ideal timeframe may still be useful, but they become less accurate.

How is the screening performed?
  1. The test must be done 1-3 days after birth.
  2. Ask your paediatrician to order the test.
  3. A trained sister will come to you to take the test.
  4. A few drops of blood will be taken from your baby’s heel. In some cases, instead of a heel prick, blood may be drawn from the baby’s vein and put on a special blotting card.
  5. The card will be couriered to the Centre for Human Metabolomics at the North-West University where the testing will be done.
  6. Your paediatrician will contact you with the result.
What if my baby's result is abnormal?

If something is found to be abnormal with the results, a repeat test and sometimes additional blood and urine tests may be required. The request for further testing must not alarm you as it does not mean that there is something wrong with your baby.

Often, when the first test suggests a problem, the results cannot be considered final until a repeat test is done. This requires a new blood sample. Your paediatrician will discuss the need for further tests with you.

When will I know the results of the test?

You will be notified of the result within 7 working days of the test being done.

What happens if my baby is diagnosed with a disorder?

If a test comes back positive for any of the disorders, your paediatrician will contact you immediately. Each disorder is treatable in its own way even though they are not curable. Your paediatrician will guide you through the explanation of the disease and the ways in which it can be treated.

How are these conditions treated?

In most instances treatment consists of dietary modifications, dietary supplementation, hormones and sometimes medication. If your baby has one of these conditions, it is very important that treatment is started as soon as possible.

Are there risks involved in Newborn Screening?

The baby will feel a little discomfort during the blood collection procedure and may cry a bit. The testing is not harmful at all.

What conditions are screened for?

24 conditions are screened for in the Newborn Screen, including:

Amino Acid Disorders

  1. Citrullinaemia, Type 1
  2. Classic Phenylketonuria
  3. Homocystinuria
  4. Maple Syrup Urine Disease
  5. Tyrosinaemia, Type 1

Organic Acid Disorders

  1. 3-Hydroxy-3-Methyglutaric Aciduria
  2. 3-Methylcrotonyl-CoA Carboxylase Deficiency
  3. Glutaric Acidaemia Type I
  4. Holocarboxylase Synthase Deficiency
  5. Isovaleric Acidaemia
  6. Methylmalonic Acidaemia (Cobalamin disorders)
  7. Methylmalonic Acidaemia (methylmalonyl-CoA mutase)
  8. Propionic Acidaemia
  9. B-Ketothiolase Deficiency

Disorders of Fatty Acid Oxidation

  1. Carnitine Uptake Defect/Carnitine Transport Defect
  2. Long Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency

(LCHAD)

  1. Multiple Acyl-CoA Dehydrogenase Deficiency

(MADD or Glutaric Acidaemia Il)

  1. Medium-chain Acyl-CoA Dehydrogenase Deficiency
  2. Very Long-chain Acyl-CoA Dehydrogenase Deficiency

Disorders of Carbohydrate Metabolism

  1. Classic Galactosaemia

Endocrine Disorders

  1. Congenital Adrenal Hyperplasia
  2. Primary Congenital Hypothyroidism

Other Disorders

  1. Biotinidase Deficiency
  2. Cystic Fibrosis

Newborn Screening (South Africa)
DRIED BLOOD SPOT

Newborn Screening (International)
DRIED BLOOD SPOT

Newborn Screening (South Africa)
DRIED BLOOD SPOT

Description

Carnitines: Free carnitine (C0), Acetyl (C2)-, Propionyl (C3)-, Butyryl (C4)-, Isovaleryl (C5)-, 3-Hydroxyisovaleryl (C5OH)-, Glutaryl (C5DC)-, Hexanoyl (C6)-, Octanoyl (C8)-, Decanoyl (C10)-, Decenoyl (C10:1)-, Myristoyl (C14)-, Tetradecenoyl (C14:1)-, Palmitoyl (C16)- and 3-Hydroxyhexadecanoyl (C16OH)-carnitine.
Amino acids: Phenylalanine, Leucine/Isoleucine, Valine, Methionine, Citrulline and Tyrosine.
Other: GALT enzyme activity, Biotinidase enzyme activity, Immunoreactive trypsinogen, 17-Hydroxyprogesterone, Thyroid stimulating hormone.

Comments

Primary disorders targeted in the newborn screening program:
Amino Acid Disorders: Classic phenylketonuria, Homocystinuria, Maple syrup urine disease, citrullinemia Type I.
Organic acid disorders: Isovaleric acidemia, Propionic acidemia, Methylmalonic acidemia, Glutaric acidemia type I, Holocarboxylase synthase deficiency, 3-Methylcrotonyl-CoA carboxylase deficiency, 3-Hydroxy-3-methyglutaric aciduria, ß-Ketothiolase deficiency.
Fatty acid oxidation disorders: Medium-chain acyl-CoA dehydrogenase deficiency, Very-long-chain Acyl-CoA dehydrogenase deficiency, Long-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency/Trifunctional protein deficiency, Carnitine uptake defect/Carnitine transport defect.
Other: Classic galactosemia, Congenital adrenal hyperplasia, Primary congenital hypothyroidism, Biotinidase deficiency, Cystic fibrosis.

The primary disorders are diseases for which testing has a high diagnostic accuracy and where early intervention improves outcome. Note however that the test is a screening test. A negative result does not completely exclude the primary disorders. Due to the non-specific nature of metabolic markers, diseases other than the primary disorders, may be identified. Tyrosinemia type I has been removed from the list of primary screening disorders because the diagnostic accuracy of tyrosine was shown to be insufficient. Immunoreactive trypsinogen is an unreliable screening test for cystic fibrosis when meconium ileus is present.

Sample requirements, viability, stability:

Whatman 903 dried blood spot card with 4 blood spots. Cards must be sent on a separate requisition number and should not include any other requests/samples. Samples must be collected according to the NBS sample collection standard operating procedure, 24-72 hours after birth. EDTA samples are not viable for NBS testing. Air dry collected samples for at least two hours before placing in a sealed paper envelope. Collected samples should be kept at room temperature. Avoid high humidity and temperatures. Samples must reach the CHM within two days from collection.

Information Required with sample(s):

Information that is required for the interpretation of the results:
1. Name and surname on both the dried blood card and the requisition form.
2. Date and time of birth.
3. Date and time of sample collection. Note that interpretation of the results requires the age of the patient to the nearest hour at the time of sample collection
4. Weight and gestational age at birth.
5. Gender, Feeding (please indicate the use of lactose free formulations) & Ethnicity
6. Specify the use of maternal steroids, antibiotics, Anticonvulsants, L-Carnitine, TPN and blood transfusions.
7. Specify if the collection is a first or repeat collection.
Absent clinical details may affect the interpretation of results and recommendations.

Newborn Screening (International)
DRIED BLOOD SPOT

Description

Carnitines: Free carnitine (C0), Acetyl (C2)-, Propionyl (C3)-, Butyryl (C4)-, Isovaleryl (C5)-, 3-Hydroxyisovaleryl (C5OH)-, Glutaryl (C5DC)-, Hexanoyl (C6)-, Octanoyl (C8)-, Decanoyl (C10)-, Decenoyl (C10:1)-, Myristoyl (C14)-, Tetradecenoyl (C14:1)-, Palmitoyl (C16)- and 3-Hydroxyhexadecanoyl (C16OH)-carnitine.
Amino acids: Phenylalanine, Leucine/Isoleucine, Valine, Methionine, Citrulline and Tyrosine.
Other: GALT enzyme activity, Biotinidase enzyme activity, Immunoreactive trypsinogen, 17-Hydroxyprogesterone, Thyroid stimulating hormone.

Comments

Primary disorders targeted in the newborn screening program:
Amino Acid Disorders: Classic phenylketonuria, Homocystinuria, Maple syrup urine disease, citrullinemia Type I.
Organic acid disorders: Isovaleric acidemia, Propionic acidemia, Methylmalonic acidemia, Glutaric acidemia type I, Holocarboxylase synthase deficiency, 3-Methylcrotonyl-CoA carboxylase deficiency, 3-Hydroxy-3-methyglutaric aciduria, ß-Ketothiolase deficiency.
Fatty acid oxidation disorders: Medium-chain acyl-CoA dehydrogenase deficiency, Very-long-chain Acyl-CoA dehydrogenase deficiency, Long-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency/Trifunctional protein deficiency, Carnitine uptake defect/Carnitine transport defect.
Other: Classic galactosemia, Congenital adrenal hyperplasia, Primary congenital hypothyroidism, Biotinidase deficiency, Cystic fibrosis.

The primary disorders are diseases for which testing has a high diagnostic accuracy and where early intervention improves outcome. Note however that the test is a screening test. A negative result does not completely exclude the primary disorders. Due to the non-specific nature of metabolic markers, diseases other than the primary disorders, may be identified. Tyrosinemia type I has been removed from the list of primary screening disorders because the diagnostic accuracy of tyrosine was shown to be insufficient. Immunoreactive trypsinogen is an unreliable screening test for cystic fibrosis when meconium ileus is present.

Sample requirements, viability, stability:

Whatman 903 dried blood spot card with 4 blood spots. Cards must be sent on a separate requisition number and should not include any other requests/samples. Samples must be collected according to the NBS sample collection standard operating procedure, 24-72 hours after birth. EDTA samples are not viable for NBS testing. Air dry collected samples for at least two hours before placing in a sealed paper envelope. Collected samples should be kept at room temperature. Avoid high humidity and temperatures. Samples must reach the CHM within two days from collection.

Information Required with sample(s):

Information that is required for the interpretation of the results:
1. Name and surname on both the dried blood card and the requisition form.
2. Date and time of birth.
3. Date and time of sample collection. Note that interpretation of the results requires the age of the patient to the nearest hour at the time of sample collection.
4. Weight and gestational age at birth.
5. Gender, Feeding (please indicate the use of lactose free formulations) & Ethnicity.
6. Specify the use of maternal steroids, antibiotics, anti-convulsants, L-Carnitine, TPN and blood transfusions.
7. Specify if the collection is a first or repeat collection.
8. Must be collected 24-72 hours after birth.
Absent clinical details may affect the interpretation of results and recommendations.

GCxGC-TOFMS Untargeted

Compound list

Spectra identified via comparison with library spectra

NMR Untargeted

Compound list

Spectra identified via comparison with library spectra

LDL Cholesterol Subfractions

Compound list

The LDL subfraction test measures up to twelve lipoprotein fractions and subfractions (VLDL, mid-bands A-C and LDL 1 through 7)

HDL Cholesterol Subfractions

Compound list

Separates and quantifies up to 10 HDL subfractions, classified from large buoyant HDL lipoproteins (HDL-L) to small-dense HDL lipoproteins (HDL-S).