Carnitine-palmitoyltransferase 2 deficiency: novel mutations and relevance of newborn screening

We report on a newborn male, born at term after an uneventful pregnancy presenting with a pathological acylcarnitine profile in routine newborn screening on the third day of life. The profile showed characteristic elevations of C14:0-, C16:0-, C16:1- and C18:1-acylcarnitines, while the ratio of (C16 + C18:1)/C2 was increased, suggesting CPT2- or carnitine-acylcarnitine-translocase- deficiency. The acylcarnitine profile in blood taken on day 9 was normal with breast milk feeding. No dicarboxylic aciduria was found. In fibroblasts, the activity of CPT2 was decreased to 25%, overall oxidation of the long-chain fatty acids was reduced to 10% of control values. Sequence analysis of the CPT2 gene showed heterozygosity for two previously undescribed mutations in exon 4: c.748-749delAA (truncating), and c.1436A > G (p.Tyr479Cys; missense) mutations. The asymptomatic parents were found to be heterozygous, the mother carries the c.748-749delAA and the father the c.1436A > G mutation. The boy is now 2.5 years old; no clinical symptoms associated with the marked impairment of long-chain fatty acid oxidation have occurred. Confirmation of mitochondrial fatty acid oxidation defects from an initial abnormal newborn-screening by tandem mass spectrometry should include enzyme and, if possible, molecular genetic analysis despite a normal 2nd screening. Biochemical testing of urine (organic acids) may be unrevealing.