Clinical characteristics and genetic analysis of six children with carnitine palmitoyltransferase 2 deficiency.

OBJECTIVES To investigate the clinical characteristic and genetic variants of children with carnitine palmitoyltransferase 2 (CPT2) deficiency. METHODS The clinical and genetic data of 6 children with CPT2 deficiency were retrospectively analyzed. The blood acylcarnitines and genetic variants were detected with tandem mass spectrometry and whole-exon gene sequencing, respectively. RESULTS There were 4 males and 2 females and the mean age at diagnosis was 32 months (15 d~9 y). One case was asymptomatic, 2 had delayed onset, and 3 were of infantile type. Three cases were diagnosed at neonatal screening, and 3 cases presented with clinical manifestations of fever, muscle weakness, and increased muscle enzymes. Five children presented with decreased free carnitine and elevated levels of palmitoyl and octadecenoyl carnitines. CPT2 gene variants were detected at 8 loci in 6 children (4 harboring biallelic mutations and 2 harboring single locus mutations), including 3 known variants (p.R631C, p.T589M, and p.D255G) and 5 newly reported variants (p.F352L, p.R498L, p.F434S, p.A515P, and c.153-2A>G). It was predicted by PolyPhen2 and SIFT software that c.153-2A>G and p.F352L were suspected pathogenic variants, and p.R498L, p.F434S and p.A515P were variants of unknown clinical significance. CONCLUSIONS The clinical phenotypes of CPT2 deficiency are diverse. The early diagnosis can be facilitated by neonatal blood tandem mass spectrometry screening and genetic testing, and most of them have good prognosis after timely diagnosis and treatment.