Carnitine palmitoyltransferase II deficiency: a clinical, biochemical, and molecular review

Congenital deficiency of carnitine palmitoyltransferase (CPT) II has been known for at least 30 years now, and its phenotypic variability remains fascinating. Three distinct clinical entities have been described, the adult, the infantile, and the perinatal, all with an autosomal recessive inheritance pattern. The adult CPT II clinical phenotype is somewhat benign and requires additional external triggers such as high-intensity exercise before the predominantly myopathic symptoms are elicited. The perinatal and infantile forms involve multiple organ systems. The perinatal disease is the most severe form and is invariably fatal. The introduction of mass spectrometry to analyze blood acylcarnitine profiles has revolutionized the diagnosis of fatty acid oxidation disorders including CPT II deficiency. Its use in expanded neonatal screening programs has made presymptomatic diagnosis a reality. An increasing number of mutations are being identified in the CPT II gene with a distinct genotype-phenotype correlation in most cases. However, clinical variability in some patients suggests additional genetic or environmental modifiers. Herein, we present a new case of lethal perinatal CPT II deficiency with a rare missense mutation, R296Q (907G>A) associated with a previously described 25-bp deletion on the second allele. We review the clinical features, the diagnostic protocol including expanded neonatal screening, the treatment, and the biochemical and molecular basis of CPT II deficiency.