Is l-Carnitine Supplementation Beneficial in 3-Methylcrotonyl-CoA Carboxylase Deficiency?

Abstract Background: 3-Methylcrotonyl-CoA carboxylase
deficiency (3-MCCd) is an autosomal recessive disorder in
the catabolism of leucine. In the present study, we
investigated the current and prior medical condition of
patients with 3-MCCd in the Faroe Islands and their
carnitine levels in blood, urine and muscle tissue with and
without L-carnitine supplementation to evaluate the current
treatment strategy of not recommending L-carnitine supplementation to Faroese 3-MCCd patients.
Methods: Blood and urine samples and muscle biopsies
were collected from patients at inclusion and at 3 months.
Eight patients received L-carnitine supplementation when
recruited; five did not. Included patients who received
supplementation were asked to stop L-carnitine, the others
were asked to initiate L-carnitine supplementation during
the study. Symptoms were determined by review of hospital
medical records and questionnaires answered at baseline
and after the intervention.
Results: The prevalence of 3-MCCd in the Faroe Islands
was 1:2,400, the highest reported worldwide. All patients
were homozygous for the MCCC1 mutation c.1526delG.
When not administered L-carnitine, the 3-MCCd patients
(n ¼ 13) had low plasma and muscle free carnitine levels,
6.9 (SD 1.4) mmol/L and 785 (SD 301) nmol/g wet weight,
respectively. L-Carnitine supplementation increased muscle
and plasma carnitine levels to a low-normal range, 25.5 (SD
10.9) mmol/L and 1,827 (SD 523) nmol/g wet weight,
p < 0.01, respectively. Seven of the thirteen 3-MCCd
subjects suffered from self-reported fatigue with some
alleviation after L-carnitine supplementation.
Conclusion: 3-MCCd is common in the Faroe Islands.
Some symptomatic 3-MCCd patients may benefit biochemically and clinically from L-carnitine supplementation, a
more general recommendation cannot be given.