A previously undescribed mutation in CPT-II deficiency. Case report.

BACKGROUND

Carnitine palmitoyl transferase II (CPT-II) is an inner mitochondrial membrane enzyme that catalyzes the transfer of long-chain fatty acids (LCFA) from the cytoplasm to the mitochondria for its oxidation. CPT-II deficiency is an autosomal recessive disease that causes a defect in the oxidation of LCFA, thus affecting skeletal muscle and producing myalgia, weakness and rhabdomyolysis. It is the most common inherited LCFA oxidation disorder. The diagnosis in newborn is made by a screening test to study the concentration of long-chain acylcarnitines and a genetic study confirmation. Genetic studies have shown the presence of more than 100 rare mutations causing this disease. Elevated creatine kinase (CK) may also occur.

CASE REPORT

A 6-day-old girl who showed elevation of long-chain acylcarnitines in the neonatal screening study (C16: 24,1umol/L VR:<4,8; C18: 5,2umol/L VR:<1,5; (C16+C18:1)/C2: 3,9umol/L VR:<0,3; C16OH: 0,1umol/L VR:<0,06).

In the NICU, liver involvement with hepatomegaly was evident. The patient presented slight elevation of transaminases and CK with normal coagulation parameters.

RESULTS

Genetic exon study and muscle biopsy identified two different variants in heterozygosity in the CPT-II gene; c.234-1G>A, that creates a premature STOP codon, which was already described. And 341-1694C>G, that causes the loss of glycine at position 114 and the insertion of 38 amino acids with no change in the reading pattern. This mutation had not been previously described.

DISCUSSION/CONCLUSION

CPT-II deficiency is the most common inherited LCFA oxidation disorder, which can present different phenotypes that may be lethal to the newborn. The genetic study of the CPT-II gene has shown the presence of rare mutations that can cause this condition, many of which are not known. It is important, therefore, to make an early diagnosis to avoid irreversible consequences, also helping to expand the known genetic mutations that cause the different phenotypes of this disease.