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Newborn Screening and Paediatric Genetics

baby.jpgThe basic principle of Newborn Screening (NBS) is that early identification and treatment will lead to reduced morbidity and mortality and thus improved outcome.


Ontario's Newborn Screening Panel Disorders

Prior to 2006, the province of Ontario screened newborns for only three conditions:

  • phenylketonuria (PKU)
  • congenital hypothyroidism
  • hearing loss

Beginning in 2006, the Ontario Ministry of Health began a gradual expansion of the province’s Newborn Screening Panel to 29 conditions, scheduled to be completed by early 2008.

One of the reasons was the development of a new technology – tandem mass spectrometry (MS/MS). MS/MS allows for concurrent testing of multiple disorders on the same blood spot sample. Compared to older technology (i.e. Guthrie test) MS/MS has improved specificity and sensitivity.

Disorders the panel will screen for include:

  • Organic acid disorders (9): Occur when the body cannot metabolize certain amino acids and fats. Accumulation of organic acids in blood and urine leads to serious potentially preventable effects on health and development, including death.
    • Isovaleric acidemia (IVA)
    • Glutaric acidemia type 1 (GA1)
    • HMG-CoA lyase deficiency (HMG)
    • Β-ketothiolase deficiency (BKT)
    • Multiple carboxylase deficiency (MCD)
    • Methylmalonic acidemia (MMA)
    • Methylmalonic acidemia (MUT Cbl)
    • Propionic acidemia (PROP)
  • Amnio acid disorders (6): Occur when the body cannot either metabolize or produce certain amino acids. This leads to toxic accumulation of substances and serious potentially preventable effects on health and development including death.
    • Phenylketonuria (PKU)
    • Maple syrup urine disease (MSUD)
    • Tyrosinemia type 1 (TYR 1)
    • Homocystinuria (HCY)
    • Citrullinemia (CIT)
    • Argininosuccinic acidemia (ASA)
  • Fatty acid oxidation disorders (5): An inability to break down fatty acids - an essential part of the body’s ability to produce energy. Affected individuals decompensate with stress such as fever, fasting, and intercurrent illness, leading to: hypoglycemia, liver, muscle and heart disease; lethargy, seizures, coma, sudden death (SIDS).
    • Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency
    • Very long-chain acyl-CoA dehydrogenase deficiency (VLCAD)
    • Long-chain L-3-OH acyl-CoA dehydrogenase deficiency (LCHAD)
    • Trifunctional protein deficiency (TFP)
    • Carnitine uptake defect (CUD)
  • Hemoglobinopathies (3): Due to changes in either the structure or amount of hemoglobin produced that can interfere with oxygen transport. Clinical symptoms range from benign to transfusion dependent anemia or death.
    • Sickle cell disease (HbS)
    • Sickle beta thalassemia (HbSβ)
    • SC disease (HbSC)

Hemoglobinopathies are a group of genetic conditions affecting red blood cells. In general terms hemoglobinopathies can be divided into two groups:

1. Structural hemoglobinopathies - those which affect the shape of the red blood cells.

Sickle cell and related diseases – the red blood cells are elongated and curved (“sickled”). The altered shape interferes with the red blood cell’s ability to move through small vessels (i.e. in the hands and feet) causing them to become stuck, leading to a painful sickle crisis, where the tissues are deprived of oxygen. The frequency and severity of symptoms depend on the specific hemoglobin variant involved i.e. hemoglobin S, hemoglobin C, hemoglobin D, etc.
2. Quantitative hemoglobinopathies – those which affect the amount or quantity of red blood cells produced.

Alpha and beta thalassemias - not enough viable red blood cells are produced and the body cannot transport enough oxygen to the tissues. Severity of the disease varies and may depend on the specific gene mutations involved. Affected individuals have microcytic hypochromic anemia and hepatomegaly. Treatment consists of regular blood transfusion and iron chelation therapy. In severe cases of alpha thalassemia known as Hb Barts, most do not survive the newborn period.

  • Endocrine disorders (2): The body does not produce enough of specific hormones needed for normal growth and development.
    • Congenital hypothyroidism (CH)
    • Congenital adrenal hyperplasia (CAH)

  • Hearing loss (1)

  • Other disorders (3):
    • Galactosemia (GAL)
    • Biotinidase deficiency (BIOT)
    • Cystic fibrosis (CF)

There are no specific Canadian guidelines for newborn screening (NBS), so NBS panels vary across Canada. The most recent guidelines for expanded newborn screening come from the American College of Medical Genetics.

The article Newborn Screening Toward a Uniform Screening Panel and System (Genetics in Medicine 2006; 8(5): Suppl 1- 250), includes a discussion of the strength of evidence for primary and secondary targets of NBS panels.

Newborn Screening Results

Screen positive means the infant is at increased risk for the disorder indicated on the report. Further testing is needed to confirm the diagnosis. This does not mean that the infant is affected.

Screen negative means the infant is not at increased risk for the disorder indicated on the report. In rare cases newborn screening can miss an affected infant. If an infant exhibits signs of a specific disorder, then diagnostic testing is indicated.