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Newborn Screening
Disorders Screened by the Expanded Ontario Newborn Screening Program
Metabolic Disorders
Organic Acid Disorders – nine disorders
Organic Acidemias (OA) are a class of inherited metabolic disorders that occur when the body cannot metabolise certain amino acids and fats. This leads to an accumulation of organic acids in the blood and urine, which can cause serious health problems. Clinical symptoms of OAs may include acute encephalopathy, vomiting, metabolic acidosis, ketosis, dehydration or coma, hyperammonemia, lactic acidosis, hypoglycemia, failure to thrive, hypotonia, global developmental delay, sepsis, hematological disorders, and death. Newborns with OAs are perfectly healthy at birth, but may become quite ill within the first few days of life, even before the results of the newborn screening are known. Treatment often involves a low protein diet and/or a diet low in specific amino acids and/or dietary supplements (such as carnitine, biotin, riboflavin, or other medications). It is very important for affected individuals to avoid fasting. Included in the OAs for which Ontario screens are: isovaleric acidemia (IVA), glutaric acidemia type 1 (GA1), HMG-CoA lyase deficiency (HMG), multiple carboxylase deficiency (MCD), methylmalonic acidemia (also known as mutase (MUT) deficiency), 3-Methylcrotonyl-CoA carboxylase (MCC) deficiency, propionic academia (PROP), and ß-Ketothiolase (BKT) deficiency.
Fatty Acid Oxidation Defects (FAODs) –five disorders
The breakdown of fatty acids in the mitochondria is an essential part of the body’s ability to produce energy, especially if an infant has nothing to eat for more than a few hours, for instance, during illness. Fatty acids are transported into the cell and then into the mitochondria. Once in the mitochondria, the carbon chains of fatty acids are metabolized two at a time, using specific enzymes. If the transporter molecule(s) or any of the enzymes used to reduce the number of carbons in the chain are missing, an accumulation of fatty acids in the body occurs and causes hypoketotic hypoglycemia and tissue damage, especially liver, muscle, and heart disease. Lethargy, seizures, coma, and sudden death are also signs of FAODs. An undiagnosed FAOD can present as sudden infant death syndrome (SIDS). Dietary supplementation with carnitine and/or cornstarch may also be part of the treatment for FAODs. It is very important for affected individuals to avoid fasting. Included in the FAODs for which Ontario screens are: Medium chain acyl-CoA dehydrogenase (MCAD) deficiency, very long chain acyl-CoA dehydrogenase (VLCAD) deficiency, long chain 3-Hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, trifunctional protein (TFP) deficiency, and carnitine uptake defect (CUD).
Amino Acid Disorders – six disorders
These disorders occur when the body cannot either metabolise or produce certain amino acids, resulting in the toxic accumulation of some substances and the deficiency of other substances. Amino acids are derived from protein. Treatment often involves a low protein diet and/or a diet low in specific amino acids. Specific medications and/or vitamins may also be prescribed, depending on the disorder. It may also be important for affected individuals to avoid fasting.
Phenylketonuria (PKU) is a condition in which individuals cannot use phenylalanine properly so it builds up in the blood (hyperphenylalaninemia). Without treatment, phenylalanine accumulation will cause severe and irreversible developmental disabilities, eczema, and other problems. Ontario has screened for PKU since 1965.
Tyrosinemia (TYR) occurs when tyrosine cannot be properly metabolised, leading to an accumulation of this amino acid and its metabolites in the liver, kidneys, and the central nervous system, causing liver disease and other problems.
Homocystinuria (HCY) occurs when homocystine accumulates in the urine. It is caused most commonly by a deficiency in an enzyme called cystathionine beta-synthase (CBS). Affected babies can have developmental disabilities and failure to thrive. They may also develop eye problems, skeletal problems, and have a higher chance of developing blood clots.
Citrullinemia (CIT) and argininosuccinic acidemia (ASA) are urea cycle defects. The urea cycle is the body’s system for excreting waste nitrogen and ammonia, and for synthesizing arginine and urea. Hyperammonemia results when one of the enzymes in the urea cycle functions improperly. Symptoms can include lethargy, vomiting, coma, seizures, liver disease, failure to thrive, and death.
Maple syrup urine disease (MSUD) occurs when the amino acids, leucine, isoleucine, and
valine cannot be metabolised. Symptoms include poor feeding, lethargy, convulsions, and even death. The urine of an affected child can have the odour of burnt sugar or maple syrup, giving the disorder its name.
Biotinidase deficiency (BIOT)
Biotinidase is essential for the recycling of the vitamin biotin, which in turn is an enzyme cofactor. These enzymes, the carboxylases, are important in the production of certain fats and carbohydrates and for the breakdown of proteins. Features of this disorder include neurological symptoms, such as developmental disabilities and seizures, and cutaneous symptoms, such as hair loss and skin rash, which can be effectively treated with biotin supplementation.
Galactosemia (GALT)
Lactose is the main sugar in breast milk, cow’s milk, and many infant formulas. This sugar is metabolised into glucose and galactose in the intestine. Individuals with galactosemia are not able to break down galactose. This can result in life-threatening complications including feeding problems, failure to thrive, liver damage, bleeding, and sepsis in untreated infants. A diet restricted in lactose is very effective in preventing these complications. Even with early treatment, however, children with galactosemia are at increased risk for developmental disabilities, speech problems, abnormalities of motor function and, in females, premature ovarian failure.
Blood Disorders: Sickle Cell Disease and Other Hemoglobinopathies
The primary goal of hemoglobinopathy screening is diagnosis of sickle cell disease (SCD) and sickle cell variants in the newborn period, before symptoms occur, in order to lower morbidity and mortality. Individuals with other hemoglobin variants can also be identified. Symptoms of hemoglobinopathies can include blockage of blood vessels leading to painful crises, increased susceptibility to infection, hemolysis, anemia,and other problems. Treatment can involve blood transfusions and subsequent iron chelation therapy. Certain vitamins and medications, such as folic acid and hydroxyurea, may also be prescribed.
Cystic Fibrosis (CF)
The presentation of CF is variable, with mild to severe forms of the disease. Individuals with CF can develop respiratory problems and infections because the lungs are clogged with mucus. The mucus also obstructs the pancreas, preventing digestive enzymes from being released into the stomach and resulting in malabsorption and malnutrition. The sweat glands are also affected in CF; individuals with the disease will have sweat with higher chloride concentrations, a phenomenon which forms the basis for diagnostic sweat chloride testing. Individuals with CF (especially males) may have reduced fertility. Early detection of CF permits immediate treatment and optimum physical growth of the child, thus reducing later health complications. Some babies will be identified as CF carriers by the screening and diagnosis process.
Endocrine Disorders
Congenital hypothyroidism (CH)
CH can cause developmental disabilities and failure to thrive if not recognized and treated. It is a relatively common condition and is the result of a thyroid hormone deficiency. Ontario has screened for CH by measuring thyroid stimulating hormone (TSH) levels in blood since 1978. Thyroid hormone replacement is a very effective treatment.
Congenital adrenal hyperplasia (CAH)
CAH is an inherited defect in which the adrenal gland cannot make cortisol and overproduce male hormones. Without cortisol, infants may be unable to regulate salt and fluids, and can die. Some newborns with CAH can be symptomatic at birth with virilisation of females. Replacement of deficient hormones is an effective means of preventing a salt-wasting crisis and preventing long-term complications.
For more information about these disorders, please consult the disorder fact sheets.
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