Maternal systemic primary carnitine deficiency uncovered by newborn screening: clinical, biochemical, and molecular aspects

Genet Med. 2010 Jan;12(1):19-24. doi: 10.1097/GIM.0b013e3181c5e6f7.


Background: Systemic primary carnitine deficiency is an autosomal recessive disorder of the carnitine cycle caused by mutations in the SLC22A5 gene that encodes the carnitine transporter, organic cation transporter. Systemic primary carnitine deficiency typically presents in childhood with either metabolic decompensation or cardiomyopathy. We report five families in which low free carnitine levels in the infants' newborn screening have led to the diagnosis of maternal systemic primary carnitine deficiency.

Methods: Blood samples from the infants and /or their family members were used to extract the DNA. The entire coding regions of the SLC22A5 gene were sequenced. The clinical data were obtained from the referring metabolic specialists.

Result: Sequencing the SLC22A5 gene allowed molecular confirmation with identification of three novel mutations: c.1195C>T (p.R399W), c.1324_1325GC>AT (p.A442I), and c.43G>T (p.G15W). All infants were asymptomatic at the time of diagnosis, and one was found to have systemic primary carnitine deficiency. Three mothers are asymptomatic, one had decreased stamina during pregnancy, and one has mild fatigability and developed preeclampsia.

Discussion: These findings provide further evidence that systemic primary carnitine deficiency presents with a broad clinical spectrum from a metabolic decompensation in infancy to an asymptomatic adult. The maternal systemic primary carnitine deficiency was uncovered by the newborn screening results supporting the previous notion that newborn screening can identify some of the maternal inborn errors of metabolism. It also emphasizes the importance of maternal evaluation after identification of a low free carnitine level in the newborn screening.

MeSH terms

  • Adult
  • Carnitine / blood
  • Carnitine / deficiency*
  • Child, Preschool
  • Family
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Newborn, Diseases / blood
  • Infant, Newborn, Diseases / diagnosis*
  • Mass Screening
  • Maternal-Fetal Exchange
  • Mutation
  • Neonatal Screening / methods*
  • Organic Cation Transport Proteins / genetics
  • Pregnancy
  • Solute Carrier Family 22 Member 5


  • Organic Cation Transport Proteins
  • SLC22A5 protein, human
  • Solute Carrier Family 22 Member 5
  • Carnitine