ClinVar

In 8 unrelated patients with familial recurrent myoglobinuria due to carnitine palmitoyltransferase II deficiency (255110), Taroni et al. (1993) identified a homozygous 439C-T transition in the CPT2 gene, resulting in a ser133-to-leu substitution (S133L). One of the patients had been reported by DiDonato et al. (1978). Among a total of 25 patients with the disorder, Taroni et al. (1993) found the S113L mutation in 56% of the mutant CPT II alleles and concluded that the S113L missense mutation is the most frequent change found in the myopathic form of CPT II deficiency. One Dutch patient was compound heterozygous for the S113L mutation and the R631C (600650.0001) mutation. In vitro functional expression studies showed that the S113L mutation resulted in normal protein synthesis, but a markedly reduced steady-state level, indicating decreased stability of the mutant protein.

By in vitro functional analysis in fibroblasts, Bonnefont et al. (1996) showed that the S113L mutation resulted in 20% CPT II residual activity with no consequence on long-chain fatty acid (LCFA) oxidation, whereas the Y628S mutation (600650.0005), found in the more severe infantile form of the disorder (600649), resulted in 10% CPT II residual activity and markedly impaired LCFA oxidation. Bonnefont et al. (1996) concluded that CPT II activity must be reduced below a critical threshold for LCFA oxidation in fibroblasts to be impaired. This critical threshold differs among tissues, thus providing a basis for the phenotypic heterogeneity of CPT II deficiency.

In 3 related patients with CPT II deficiency from consanguineous marriages, 2 sibs and a first cousin, Handig et al. (1996) identified homozygosity for the S113L mutation. The cases could be traced back to a common ancestral couple 5 generations earlier. The family showed clinical variability of the disorder.

Martin et al. (1999) identified the S113L mutation in 8 of 14 Spanish patients from 10 unrelated families. Seven patients were homozygous for the mutation, 1 patient was heterozygous, and 6 patients did not carry the mutation on either allele. The mutation was found in the heterozygous state in 7 healthy relatives belonging to 3 different families.

Joshi et al. (2012) reported 2 unrelated patients with stress-induced myopathic carnitine palmitoyltransferase II deficiency who were heterozygous for the S113L mutation. One patient, a 21-year-old female professional tennis player, suffered from exercise-induced attacks of muscle pain, burning sensations, and proximal weakness. The other patient, a 30-year-old male amateur marathon runner, developed muscle cramps and rhabdomyolysis upon extensive exercise and insolation-induced fever.