Newborn screening may fail to identify intermediate forms of maple syrup urine disease

Abstract

The New South Wales state-wide newborn screening programme has offered comprehensive screening for inborn errors of metabolism, including MSUD, using electrospray tandem mass spectrometry since 1998. Over this period, a number of patients with classic MSUD have been identified with subsequent good neurological outcome. We describe two patients with an intermediate form of MSUD who presented later in childhood. Retrospective review of their newborn screening results demonstrates that the diagnosis could not have been made by current newborn screening. Their neurological outcome is much less satisfactory. Despite the usefulness of expanded newborn screening programmes in detecting severe neonatal presentations of inborn errors of metabolism, partial enzyme deficiencies may not be detected. Metabolic diseases still need to be considered in appropriate clinical situations later in life.

Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: A worldwide collaborative project

“…The choice of a slightly higher limit is driven by the recognition that false negative cases have been encountered in virtually all conditions. 28 -30 Once the possibility of a cutoff value set too high has been considered, 31 it must be recognized that a small number of cases could just be undetectable on the sole basis of their biochemical phenotype. Although this is unfortunate, the quest for perfect sensitivity should not be a reason to artificially set cutoff values so close to the …”

Genetic Screening

“…False-negative results are also minimized by ensuring that the sample is collected at least 24 hours after birth, and some states collect a second sample 1-2 weeks after birth (19). This effort appears to be successful, in that false-negative rates for most conditions appear to be very low (63)(64)(65)(66).…”

Branched Chain Amino Acids and Maple Syrup Urine Disease

“…However, the chronic increases in leucine and keto acids result in developmental delays and because these patients are unlikely to present clinically and start treatment early, developmental outcomes are often worse than neonatal presenting cases [ 21 ].…”

“…Plasma leucine concentration at commencement of treatment was also lower; mean 2,100 μmol/L in cases identifi ed on screening, 2,873 μmol/L in clinically presenting cases. However, newborn screening may fail to identify intermediate and intermittent forms of the condition [ 21 ] so MSUD still needs to be considered in appropriate clinical situations later in life.…”