Tandem mass spectrometry has become increasingly popular as the preferred technology for detecting inborn errors of metabolism in newborn screening programmes. Its sensitivity and specificity for detecting numerous inborn errors has been well documented. However, there are continuing questions about whether the technology should be used to the fullest when such usage may mean detecting and reporting analytical findings that could lead to diagnosing conditions for which clinical outcome is unclear and treatment may not be needed, or treatment efficacy may not yet be proven and cost effectiveness is unlikely. As part of a friendly debate to educate conference attendees on both sides of somewhat controversial issues, these 2 papers at the conference presented some of the information supporting or questioning the cost effectiveness of full scan usage and reporting in tandem mass spectrometry newborn screening. Reported here are some of the questioning arguments.
Cost-Benefit Analysis ; Humans ; Infant, Newborn ; Infant, Newborn, Diseases ; diagnosis ; economics ; Neonatal Screening ; economics ; Tandem Mass Spectrometry ; economics

Carnitine is necessary for transport of long-chain fatty acids into mitochondria, to enter the beta-oxidation cycle. Four carnitine cycle defects have been described. The carnitine transporter mediates carnitine transport across the plasma membrane. Symptoms include hypoketotic hypoglycaemia and cardiomyopathy. Some affected subjects are asymptomatic. Newborn screening detects very low levels of free carnitine in some but not all. Carnitine palmitoyltransferase type IA (CPTI) transports long-chain fatty acyl-CoAs across the outer mitochondrial membrane. Affected infants have hypoketotic hypoglycaemia with catabolic stress, but otherwise remain well. Newborn screening tests reveal elevated free carnitine, (elevated C0/C16+C18). Sensitivity is unclear and confirmation needs leukocyte or fibroblast assays. Carnitine-acylcarnitine translocase transfers fatty acylcarnitines across the inner mitochondrial membrane. The most common presentation is sudden death in the first days. Carnitine palmitoyltransferase type II (CPTII) converts long-chain acylcarnitines to long-chain acylCoAs for beta-oxidation. Severe deficiency is lethal. Newborn screening for both disorders reveals elevated palmitoylcarnitine and enzymology or mutation analysis is needed for diagnosis. Late-onset CPTII is the most common disorder, presenting as muscle pain and rhabdomyolysis on severe exercise. All 4 disorders can be detected by newborn screening, with variable sensitivity. Late-onset CPTII probably cannot be detected. Carnitine transporter, CPTI and late-onset CPTII have proven treatment strategies.
Carnitine ; metabolism ; Carnitine O-Palmitoyltransferase ; deficiency ; Humans ; Infant, Newborn ; Metabolism, Inborn Errors ; diagnosis ; enzymology ; Neonatal Screening

Over the last 40 years newborn screening has been an undoubted success and many thousands of children have been saved from mental retardation and other problems because of early diagnosis of their disorders. Now many diseases can be diagnosed early by newborn screening and many more are on the horizon. It must be a long-term goal to extend newborn screening tests to all children but, in areas of the world where healthcare delivery is insufficient, solving other health problems has to take precedence over introducing newborn screening. If it is decided to introduce newborn screening in a region where currently there is none screening for congenital hypothyroidism alone should be started before anything else at all is attempted so that proper systems can be put in place. There is an exciting future for newborn screening ahead. If new programmes are approached with proper caution maximal benefit will be achieved from newborn screening, which is one of the few clearly effective preventive strategies in healthcare.
Child ; Child Welfare ; Humans ; Infant, Newborn ; Neonatal Screening ; standards