Carnitine palmitoyltransferase II (CPT II) deficiency: genotype-phenotype analysis of 50 patients

J Neurol Sci. 2014 Mar 15;338(1-2):107-11. doi: 10.1016/j.jns.2013.12.026. Epub 2013 Dec 23.


Clinical, biochemical and molecular genetic data in a cohort of 50 patients with muscle CPT II deficiency are reported. Attacks of myoglobinuria occurred in 86% of patients. In 94% of patients the triggering factor was exercise. Although the myopathic form is often called the adult from, in 60% of patients, the age of onset was in childhood (1-12 years). All the patients in whom biochemical activity was measured had normal enzyme activity of total CPT I+II but the activity was significantly inhibited by malonyl-CoA and Triton. The p.S113L mutation was detected in 38/40 index patients (95%) in at least one allele. Sixty percent of index patients were homozygous for this mutation. Thirteen other mutations, all in compound heterozygote form, were also identified. There was no significant difference in ages of onset, clinical and biochemical phenotype of patients with p.S113L mutation in homozygous or compound heterozygous form. The exception was a tendency of slightly higher residual enzyme activity upon malonyl-CoA inhibition in compound heterozygotes. Phenotype was also not significantly different in patients with missense mutations on both alleles and patients with truncating mutation on one allele and missense mutation on the other allele. However, the only exception was that, attacks were triggered by fasting in almost all the patients with truncating mutations. In contrast, fasting triggered the attacks only in one third of patients with missense mutations on both alleles. The data indicate that within the muscle form of CPT II deficiency, the various genotypes have only marginal influence on the clinical and biochemical phenotype.

Keywords: CPT II; Exercise; Genotype–Phenotype; Mutation; Myoglobinuria; PCR.

MeSH terms

  • Adolescent
  • Adult
  • Carnitine O-Palmitoyltransferase / deficiency*
  • Carnitine O-Palmitoyltransferase / genetics*
  • Child
  • Child, Preschool
  • Female
  • Genetic Association Studies
  • Genotype
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Metabolism, Inborn Errors / genetics*
  • Muscles / pathology*
  • Mutation / genetics*
  • Phenotype*
  • Young Adult


  • Carnitine O-Palmitoyltransferase

Supplementary concepts

  • Carnitine palmitoyl transferase 2 deficiency