Carnitine transporter defect: Diagnosis in asymptomatic adult women following analysis of acylcarnitines in their newborn infants

Abstract

Carnitine transporter defect (CTD) is an autosomal recessive disorder characterized by episodes of non-ketotic hypoglycaemia, hyperammonaemia and liver disease, or by the development of cardiomyopathy, both of which occur in infancy and childhood. Blood carnitine concentrations are extremely low. The diagnosis can be confirmed by finding abnormal fat oxidation and carnitine uptake in skin fibroblasts. The condition has not previously been thought to present later in life or to be benign. We report the identification of four women discovered to have CTD as a consequence of finding low carnitine concentrations in the cord blood or newborn samples from their infants. All four mothers had been asymptomatic and none had a cardiomyopathy.

Abnormal Newborn Screening in a Healthy Infant of a Mother with Undiagnosed Medium-Chain Acyl-CoA Dehydrogenase Deficiency

“…Thus, maternal MCADD (Leydiker et al 2011), CTD (De Biase et al 2012;El-Hattab et al 2010;Lee et al 2010;Lund et al 2012;Schimmenti et al 2007;Vijay et al 2006), glutaric acidemia type I (Crombez et al 2008), and combined homocystinuria and methylmalonic aciduria (Lin et al 2009) have all been detected through NBS by the finding of decreased free carnitine in the newborn. In addition, elevated specific acylcarnitines in newborns have revealed maternal 3-methylcrotonyl-CoA carboxylase deficiency (Gibson et al 1998;Koeberl et al 2003;Lund et al 2012), very long-chain acyl-CoA dehydrogenase deficiency (McGoey and Marble 2011), holocarboxylase synthetase deficiency (Nyhan et al 2009), and multiple acyl-CoA dehydrogenation deficiency due to a riboflavin transporter gene defect (Chiong et al 2007;Ho et al 2011).…”

The Risk of Fatty Acid Oxidation Disorders and Organic Acidemias in Children with Normal Newborn Screening

“…The potential high local incidence of false-positive cases in diseases such as of VLCADD, CPT-1, 3-MCC, IVA, citrulinaemia and maternal CUD (Ensenauer et al 2004;Vijay et al 2006;Glamuzina et al 2011;Ryder et al 2016;Rips et al 2016) and the local workforce capacity particularly in the first few years of that contributed to the NMSP adopting relatively high cut-off levels. This results in less work for the screening laboratory, fewer second tests and less false-positive cases, thus limiting unnecessary stressful notifications to families.…”

Neonatal Screening for Primary Carnitine Deficiency: Lessons Learned from the Faroe Islands

“…Because carnitine is transferred from the placenta to the fetus during pregnancy, an infant's carnitine levels during the neonatal period reflect those of the mother [23]. Thus, unaffected infants born to affected mothers can have low carnitine levels shortly after birth [4][5][6]24]. The diagnosis of primary carnitine deficiency can be biochemically confirmed by measuring plasma free and total carnitine that are all (free, acylated and total carnitine) low in affected patients [2,23].…”

“…The diagnosis of primary carnitine deficiency can be biochemically confirmed by measuring plasma free and total carnitine that are all (free, acylated and total carnitine) low in affected patients [2,23]. Plasma carnitine levels should be measured in all mothers of infants found to have low free carnitine levels on newborn screening in order to determine if the mother (rather than the infant) or if both mother and infant have primary carnitine deficiency [4][5][6]24].…”