Supplemental Material: e-Patients
Pt. 1: This 55 year old woman had symptoms at 1 yr of age involving rigidity and muscle pain with fever lasting 3 days. Subsequently, she had multiple episodes of rhabdomyolysis, triggered by fasting, infection, menstruation, and other stresses. By her mid-thirties, the episodes had become more severe and she developed renal failure from which she recovered. After this, her physical endurance continued to deteriorate and CPT II deficiency was documented at age 50 years by lymphocyte enzyme assay: 0.17 nmol palmitoylcarnitine /min/mg protein (normal mean+/-SD: 0.92 +/- 0.32). DNA mutation analysis: homozygous for S113L (338C>T). She was previously treated with a low fat, increased carbohydrate diet. She received the triheptanoin diet for 61 months.
Pt. 2: This 54 year old man had muscle cramps and pain following exercise dating back to his teen years. His first episode of rhabdomyolysis occurred at age 20 years when he had mononucleosis. Thereafter He had multiple episodes following exercise. The diagnosis was finally established at age 42 years. He was unable to work from age 46 years. Treatment consisted of a low fat- high carbohydrate diet with carnitine supplementation. This regimen did not prevent further episodes of rhabdomyolysis or muscle pain even with limited exercise. Enzyme assay (fibroblasts) revealed 0.11 nmol palmitoylcarnitine/min/mg protein(normal: 0.99 +/- 0.12 mean +/- 1 SD). DNA mutation analysis revealed Q151R (452G>A) and S113L (338C>T). He received the triheptanoin diet for 40 months.
Pts. 3, 4, 5: This family had 3 affected children, 2 girls now aged 17 (Pt. 3) and 13 years (Pt. 4) and one boy (Pt. 5) aged 10 years. Early concerns about episodes of hypoglycemia prompted testing that showed that all 3 children had carnitine deficiency for which they were supplemented. Acylcarnitine analysis was normal. A low fat, high carbohydrate diet with MCT oil supplementation was recommended.
The eldest, (Pt. 3), had had numerous episodes of hypoglycemia from age 17 months that required many hospitalizations. By age 13 years, she was hospitalized 3 times for rhabdomyolysis. Lymphocyte assay for CPT II revealed 0.11nmol palmitoylcarnitine/min/mg protein(normal 1.16 +/- 0.43 mean +/- 1 SD). She received triheptanoin for 52 months.
Pt. 4 had occasionally complained of transient leg pain but was never hospitalized. She received triheptanoin for 45 months. Her brother, Pt. 5, had been hospitalized twice for hypoglycemia between 2 and 3 years of age. Although he had occasionally complained of transient leg pain with exercise, he was not hospitalized. He also received triheptanoin for 45 months. Results of lymphocyte CPT II assays for Pt. 4 and Pt. 5 were both 0.13 nmol palmitoylcarnitine/min/mg protein. DNA mutation analysis from all 3 children revealed R631C (1891C>T) and R124X (370C>T).
Pt. 6: This 30 year old man had symptoms of muscle pain with exertion, rhabdomyolysis, and weakness beginning at age 13 years. He estimates that he has had 1-3 episodes of weakness and muscle aches per month while he has more severe episodes monthly, usually following exercise but only once requiring hospitalization. The recommended low fat, high carbohydrate diet with exercise restriction was not effective. Muscle CPT II assay at age 13 years revealed a level of 12.3 nmol palmitoylcarnitine/min/gm wet wt. (normal range: 23-177). DNA mutation analysis revealed S113L (338C>T) and Q413fs (1238-1239delAG). He has taken the triheptanoin diet for 9 months.
Pt. 7: This 14 year old young man had a vague history of muscle aches following physical activity for several years prior to his first three episodes of rhabdomyolysis requiring hospitalization, at age 13 years. CPK levels were in excess of 100,000 IU/L and his urine appeared red-brown to dark red on these occasions. His diet was low fat with increased carbohydrate and additional MCT oil representing ~10% of his daily caloric intake. Physical activity was restricted. This treatment was not effective. CPT II assay (fibroblasts) was 0.13 nmol palmitoylcarnitine/min/mg protein. DNA mutation analysis revealed S113L (338C>T) on one allele. (DNA sequencing analysis was not performed.) He has received triheptanoin diet therapy for 7 months.