What is Newborn Screening?

It involves laboratory testing of all newborns/infants for certain genetic/metabolic or endocrine disorders. Screening can indicate the possibility that an infant may be at risk for a disorder included in the testing panel. Additional diagnostic tests may be necessary to determine if the infant with an abnormal test actually has a disorder. Even though the defect is present at birth, the symptoms may not appear until later in life. By early screening, disease can be diagnosed much before the symptoms appear. It is noted that by the time the symptoms appear a lot of irreversible damage has already occurred. This newborn screening program also identifies at-risk infants and offers genetic counseling.

By Tandem mass spectrometry (MS/MS), screening for more than 30 disorders from a single blood spot is possible. Tandem mass spectrometer is a computer-controlled device that separates & quantities compounds based on their mass to charge ratio. From a single blood spot sample on filter paper, it can detect genetic disorders of amino acids, organic acids, and fatty acids, which typically manifest during the first two years of life as acute metabolic crisis resulting in slow growth, blindness, brain damage or possibly death. These metabolic disorders are usually triggered by infections.

Significance of Newborn Testing.

• Pre-symptomatic diagnosis of these disorders can significantly improve the long-term prognosis of affected children, by early treatment. 

• A few of these disorders cannot be treated satisfactorily. However, the possibility of early diagnosis can minimize the irreversible complications. This will prevent a lot of anxiety, wastage of time and money for parents and suffering for affected children.

• Diagnosis will also be beneficial to the patient's families for providing appropriate genetic counseling and prenatal diagnosis.

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 and the presence of co-existing illness or medical conditions. If the infant with normal screening test result 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.

Disorders detected by Tandem Mass Spectrometry

• Argininemia
• Arginosuccinic aciduria
• Citrullinemia
• Homocystinuria
• Hyperammonemia, Hyperornithinemia, Homocitrullinemia
• Maple syrup urine disease (MSUD)
• Non-ketotic hyperglycinemia
• Phenylketonuria (PKU)
• Tyrosinemia type I
• Tyrosinemia type II

2. Disorders of Organic acid Metabolism:

• Glutaric acidemia Type I
• Isovaleric acidemia
• 3-ketothiolase deficiency)
• 3-Methylcrotonyl Co-A carboxylase deficiency
• 3-Methylglutaconyl-Co A hydratase deficiency
• Multiple carboxylase deficiency
• Methylmafonic acidemias
• Propionic academia

3. Disorders of Fatty acid Metabolism:

• Short chain acyl CoA dehydrogenase (SCAD) deficiency
• Medium chain acyl-CoA dehydrogenase (MCAD) deficiency
• Mitochondrial trifunctional protein (TFP) deficiency
• Long chain 3-hydroxy acyl-CoA dehydrogenase (LCHAD) deficiency
• Very long chain acyl CoA dehydrogenase (VLCAD) deficiency
• Carnitine palmitoyl-transferase deficiency type II (CPT2)
• Carnitine-acylcarnitine translocase (CACT) deficiency
• Glutaric acidemia type II (GA-2; multiple acyl-CoA dehydrogenase deficiency)
• 2,4-Dienoyl-CoA reductase deficiency
• 3-Hydroxy-3-methylglutaryl -CoA (HMG-CoA) lyase deficiency

Method:

The Neogram Aminoacids and Acylcarnitines nonderivatized kit is used. Blood for screening is collected on a filter paper. A 3mm disc is punched out of the blood spot into a 96-well plate. Amino acids and acylcarnitines are measured after extraction using a solution containing stable-isotope labelled internal standards. This extract is then analyzed using a tandem mass spectrometer (MS/MS). The Neogram and Analyst software packages

included with the instrument system perform data acquisition and processing. The values are calculated by comparing the measured analyte intensities with  those of internal standards in the extracted solution.

Specimen Required:

5 blood spots. Take care that the blood is soaked on both sides of filter paper. Provide complete information with blue or black ballpoint pen. This information is important for interpretation & follow-up.

Reporting:

Reports with result interpretation are provided. A report for an abnormal result includes a quantitative result of the abnormal metabolites, a detailed interpretation of the results, recommendations for additional confirmatory testing ( enzyme assays, molecular testing).

For Genetic counselling:

Please contact: