Elevated neonatal 3-OH isovalerylcarnitine due to breast milk sources in maternal 3-MCC deficiency

Cellular Metabolism and Disease: What Do Metabolic Outliers Teach Us?

“…These programs have revealed a remarkable degree of phenotypic heterogeneity among individuals with abnormal levels of diagnostic metabolites, many of whom never manifest any clinical symptoms. In some cases, clinically silent “disease” has been detected in the asymptomatic mothers of babies subjected to screening programs, apparently because small amounts of the mother’s metabolites are transferred to the unaffected baby through the placenta, breast milk or other routes (Eichhorst et al, 2010). In other cases, IEMs once thought to be highly penetrant and severe now appear to be clinically silent in most individuals (Alfardan et al, 2010).…”

Maternal 3-methylcrotonyl-coenzyme A carboxylase deficiency with elevated 3-hydroxyisovalerylcarnitine in breast milk

“…Maternal 3-MCC deficiency may be found by screening for positive normal neonates who have abnormal C5-OH levels. Persistent elevation in C5-OH in the non 3-MCC deficiency neonate could result from placental transfer of C5-OH, C5-OH transfer via the breast milk, and additionally, due to inefficient clearance mechanisms for the metabolite, early in postnatal development2457). According to a national survey of extended newborn screening by LC-MS/MS in Taiwan, the overall incidence of inborn error metabolism was approximately 1 per 6,219.…”

“…In the event that the maternal and the formula-fed infant metabolite levels are both abnormal, the metabolic work up should be repeated in the infant after one month to verify after one month to verify that the infant's levels are normalizing due to clearance of prenatally transferred metabolites; and metabolic laboratory work up should be repeated again in the infant after weaning, because maternal metabolites may be transferred to the infant via breast milk3). One study revealed higher levels of C5-OH level on breast milk samples that was diluted five times with methanol prior to sample processing and quantification than blood reference range2).…”

“…It is detected in 1 out of 36,000 births, globally23). With the expansion of newborn screening programs 3-MCC deficiency has become one of the most commonly diagnosed inborn error metabolisms.…”