Neonatal Hypobetalipoproteinemia

Summary: Quantitation of cord blood low density lipoprotein cholesterol (C-LDL), kindred studies, and longitudinal assessment allows the neonatal diagnosis of familial hypobetalipoproteinemia. To assess the relationship between neonatal hypobetalipoproteinemia and C-LDL in later infancy, kindred studies with follow-up were carried out in 11 families with a hypobetalipoproteinemic neonatal propositus, and in two families with normal neonates and hypobetalipoproteinemic adult propositi. Neonatal and familial hypobetalipoproteinemia was diagnosed in one kindred by quantitation of cord blood C-LDL, four-generation vertical transmission, and by demonstration of persistent hypobetalipoproteinemia in later infancy. In a second kindred, the neonate and her father, grandfather, and half-siblings had hypobetalipoproteinemia, but her C-LDL was normal (96 mg/dl) at age 6 months. Whether this unexpectedly normal C-LDL will persist, with a resultant “false positive” diagnosis at birth, can only be determined by longitudinal study. In a third kindred the hypobetalipoproteinemic neonate retained low C-LDL at age 2 years, the mother had borderline-low C-LDL levels, but there were no living siblings or maternal first degree relatives and familial hypobetalipoproteinemia could not be confirmed. The remaining eight hypobetalipoproteinemic neonates had normal C-LDL on follow-up examination; kindred studies failed to reveal familial hypobetalipoproteinernia. Two neonates with normal cord blood C-LDL, born to hypobetalipoproteinemic parents, retained normal C-LDL levels in infancy.The recent evidence of the protective “anti-coronary risk” nature of low C-LDL (in familial hypobetalipoproteinemia) and elevated C-HDL (in familial hyperalphalipoproteinemia) has augmented interest in neonates having an exceptionally low value of C-LDL and a high value of high density lipoprotein cholesterol (C-HDL). Cord blood and kindred lipoprotein studies may identify families having heritable “anti-coronary risk” factors.Speculation: Cord blood and kindred Lipoprotein studies focused on the lower 2.5th percentile for C-LDL may identify families having heritable “anti-coronary” risk factors.