title: Clinical and biochemical heterogeneity in an Italian family with CPT II deficiency due to Ser 113 Leu mutation.
abstract: BACKGROUND
  Carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive disorder which presents with recurrent myoglobinuria. Heterozygotes are usually asymptomatic.
  
  
  METHODS
  We correlate the clinical, biochemical and molecular features of a family in which the proband is homozygous for CPT II deficiency, due to the common Ser 113 Leu mutation.
  
  
  RESULTS
  The 20-year-old female proband presented at age three years with episodic myalgia and myoglobinuria, elevated creatine kinase (CK) of 3600 IU/L and had a 33% residual CPT II activity in cultured skin fibroblasts. Her 25-year-old dizygotic twin brothers presented with muscle stiffness following prolonged exercise but no overt pigmenturia and had interictal CKs up to 662 lU/L. Her parents and a 13-year-old brother are asymptomatic. An elder sister, not investigated, had recurrent pigmenturia and died at eight years with myoglobinuria. Molecular analysis revealed that the proband is homozygous for the Ser 113 Leu mutation. Her parents are heterozygotes with CPT II activities of 55% to 70%. Her younger brother is normal with 83% activity. The symptomatic twin brother are heterozygous but demonstrated unexpectedly low CPT II activities of 40%, which may explain their phenotype.
  
  
  CONCLUSIONS
  We postulate that there may be genetic, environmental and sex hormonal factors accounting for this manifesting heterozygosity and biochemical heterogeneity in CPT II deficiency.
authors.affiliation: Department of Pediatrics, The Hospital for Sick Children , University of Toronto, Toronto, Ontario.
authors.forename: Mubeen F
authors.initials: MF
authors.lastname: Rafay
authors.forename: E Gordon
authors.initials: EG
authors.lastname: Murphy
authors.forename: J Denis
authors.initials: JD
authors.lastname: McGarry
authors.forename: Petra
authors.initials: P
authors.lastname: Kaufmann
authors.forename: Salvatore
authors.initials: S
authors.lastname: DiMauro
authors.forename: Ingrid
authors.initials: I
authors.lastname: Tein
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D002334:Carnitine O-Palmitoyltransferase / Q000172:deficiency* / Q000235:genetics*; D003402:Creatine Kinase / Q000097:blood; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D006579:Heterozygote; D006801:Humans; D007558:Italy; D008297:Male; D018908:Muscle Weakness / Q000209:etiology / Q000235:genetics; D009135:Muscular Diseases / Q000209:etiology / Q000235:genetics; D009154:Mutation / Q000235:genetics / Q000502:physiology; D009460:Neurologic Examination; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004247:DNA; D002334:Carnitine O-Palmitoyltransferase; D003402:Creatine Kinase