Abstract 

Carnitine palmitoyltransferase (CPT) II deficiency disorders are causer by defects in the transport of long-chain fatty acids into the mitochondrion.  The disorders have variable clinical outcomes ranging from a rare lethal infantile disease to a relatively mild, usually adult-onset, disorder with muscle pain and stiffness triggered by exertion, fasting, or viral infection.  Two sisters, aged 24 and 29 years, exhibited onset of variable symptoms of the mild myopathic disorder beginning at 7 and 16 years of age, respectively, with the younger sister experiencing more severe symptoms over her lifetime than her older sister.  Both girls were screened for mutations in the CPT II gene and found to be compounded heterozygotes for the common S113L mutation and a truncation mutation, 413fs, predicted to be lethal in the homozygous state.  They were also heterozygous for the common V368I and M647V polymorphisms.  A 30 year old sister experienced episodes of shakiness, weakness, and hot flashes following either a 3 hour or more fasting period or sleep deprivation.  She was heterozygous for the S113L mutation and homozygous for the polymorphism variants.  A 26 year old asymptomatic sister was heterozygous for the 413fs mutations and homozygous for the normal polymorphism alleles.  Residual CPT II enzyme activity in a skeletal muscle biopsy from the severely affected sister was 10% of normal.  Activity in cultured skin fibroblasts from the myopathic sisters was 10 and 17% or normal, respectively.  Palmitic acid oxidation in their fibroblasts was atypically low for the myopathic disorder on 3 of the 4 sisters including strength and endurance testing.  The results of these studies are presented including possible explanations for the variability in ages of onset and severity of symptoms.