Newborn screening: the genomic challenge

Abstract

We have just celebrated the 50th anniversary of mandatory newborn screening (NBS). Beyond any question, NBS has been a huge success. It has virtually eliminated the tragedy of intellectual disability from phenylketonuria (PKU) and congenital hypothyroidism in the developed world. It has eliminated death or profound neurologic sequelae from neonatal sepsis in galactosemia and in salt-wasting congenital adrenal hyperplasia and sickle cell disease. The clinical complications of biotinidase deficiency are now rarely encountered. Sudden death from the fatty acid oxidation disorders is almost a thing of the past. Children with homocystinuria and maple syrup urine disease can achieve their full potentials and grow into productive adults. If this can be accomplished for the metabolic and endocrine disorders, could there be even greater benefit from NBS for genetic disorders in general, including nonmetabolic genetic disorders? True, we do not have preventive therapies for chromosomal aberrations or most other genetic abnormalities but there could be many other benefits from neonatal diagnosis, such as information for the family to prepare for progressive disability in the child, for genetic counseling for family planning, for prenatal or preconceptual diagnosis in future pregnancies, for prevention of needless and expensive diagnostic odysseys in the child, and still other potential benefits (Landau et al. 2014). So, why not expand NBS into genetic screening? This probably can be done. Next-generation sequencing (NGS) could allow examination of the entire genome. The cost of the sequencing is rapidly decreasing and may soon be low enough to accommodate NBS. Potentially, every genetic alteration could be identified within a few days after birth by testing the current NBS specimen or perhaps even earlier by screening umbilical cord blood. If screening included identifications of variations considered to increased risk for common diseases such as cancer, Alzheimer's disease, or Parkinson's, the infant would also be a proxy for family members leading to their testing for at-risk variations. Newborn genetic screening sounds like a “no-brainer.”