Journal of Inherited Metabolic Disease

, Volume 37, Issue 2, pp 215–222 | Cite as

Carnitine levels in 26,462 individuals from the nationwide screening program for primary carnitine deficiency in the Faroe Islands

  • Jan Rasmussen
  • Olav W. Nielsen
  • Nils Janzen
  • Morten Duno
  • Lars Køber
  • Ulrike Steuerwald
  • Allan M. Lund
Original Article

Abstract

Background

Primary carnitine deficiency (PCD) is an autosomal recessive disorder of fatty acid oxidation and has been associated to episodes of sudden death in the Faroe Islands. Data are presented from the nationwide population based Faroese screening program to find people with low carnitine levels indicating PCD.

Methods

Whole blood samples from dried blood spots were analysed by tandem mass spectrometry with and without butylation. Genetic analyses were performed in all people with non-butylated free carnitine (fC0) below 7 μmol/L.

Results

55 % (n = 26,462) of the entire population was screened and 89 PCD patients were identified, yielding an overall prevalence of 1:297 of PCD in the Faroe Islands. Carnitine levels were positively correlated to age in both males and females (p < 0.003) although levels decreased in females when reaching fertile age. The gender difference in mean carnitine levels was significant during female fertile age (4.71 μmol/L fC0 in the age group 25–30 years, p < 0.01). A lower cut-off of 5 μmol/L in fC0 identified all homozygous for the severe genotype c.95A > G (p.N32S) (n = 20).

Conclusion

Carnitine levels differ by gender and age. A lower cut-off of 5 μmol/L in fC0 was appropriate to identify c.95A > G homozygotes. The prevalence of PCD in the Faroe Islands is the highest reported in the world (1:297).

Supplementary material

10545_2013_9606_Fig3_ESM.jpg (67 kb)
Supplementary Fig. 1a

The distribution of all tested males and females in relation to fC0 (Suppl. Fig. 1a) and total carnitine levels (Suppl. Fig. 1b) in whole blood. (JPEG 66 kb)

10545_2013_9606_Fig4_ESM.jpg (67 kb)
Supplementary Fig. 1a

The distribution of all tested males and females in relation to fC0 (Suppl. Fig. 1a) and total carnitine levels (Suppl. Fig. 1b) in whole blood. (JPEG 66 kb)

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High resolution image (TIFF 992 kb)
10545_2013_9606_MOESM2_ESM.tif (956 kb)
High resolution image (TIFF 956 kb)
10545_2013_9606_Fig5_ESM.jpg (73 kb)
Supplementary Fig. 2a

Mean fC0 (a) and total carnitine (b) (95%CI) in whole blood in males (n = 12,360) and females (n = 13,953) with increasing age. PCD (n = 89) and 3MCCD (n = 11) patients and people with traces of pivalic acid (n = 49) were excluded (JPEG 72 kb)

10545_2013_9606_Fig6_ESM.jpg (78 kb)
Supplementary Fig. 2a

Mean fC0 (a) and total carnitine (b) (95%CI) in whole blood in males (n = 12,360) and females (n = 13,953) with increasing age. PCD (n = 89) and 3MCCD (n = 11) patients and people with traces of pivalic acid (n = 49) were excluded (JPEG 72 kb)

10545_2013_9606_MOESM3_ESM.tif (985 kb)
High resolution image (TIFF 985 kb)
10545_2013_9606_MOESM4_ESM.tif (1 mb)
High resolution image (TIFF 1057 kb)
10545_2013_9606_Fig7_ESM.jpg (70 kb)
Supplementary Fig. 3

Fraction of c.95A>G/c.95A>G (black), PCD with other genotype (grey) and non-PCD (white) among all subjects with fC0 <7 micromol/L (JPEG 70 kb)

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High resolution image (TIFF 919 kb)
10545_2013_9606_Fig8_ESM.jpg (56 kb)
Supplementary Fig. 4

c.95G>A homozygotes (n = 20) illustrated twice in order to compare their values of free carnitine measured with butylation and without butylation (JPEG 56 kb)

10545_2013_9606_MOESM6_ESM.tif (919 kb)
High resolution image (TIFF 919 kb)
10545_2013_9606_MOESM7_ESM.docx (96 kb)
Supplementary Table 1(DOCX 95 kb)
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ESM 8(DOCX 108 kb)

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Copyright information

© SSIEM and Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Jan Rasmussen
    • 1
  • Olav W. Nielsen
    • 2
  • Nils Janzen
    • 3
    • 4
    • 5
  • Morten Duno
    • 6
  • Lars Køber
    • 7
  • Ulrike Steuerwald
    • 3
    • 8
  • Allan M. Lund
    • 6
    • 9
  1. 1.Department of Internal MedicineNational HospitalThorshavnFaroe Islands
  2. 2.Department of CardiologyBispebjerg University HospitalCopenhagenDenmark
  3. 3.Screening-Labor HannoverHannoverGermany
  4. 4.Department of NeuropediatricsChildren’s Hospital, Ruhr University of BochumBochumGermany
  5. 5.Clinic for Pediatric Kidney-, Liver- and Metabolic DiseasesHannover Medical SchoolHannoverGermany
  6. 6.Centre for Inherited Metabolic Disorders, Department of Clinical GeneticsRigshospitalet University HospitalCopenhagenDenmark
  7. 7.Department of CardiologyRigshospitalet University HospitalCopenhagenDenmark
  8. 8.Department of Occupational and Public HealthNational Hospital SystemThorshavnFaroe Islands
  9. 9.Department of Clinical GeneticsRigshospitalet University HospitalCopenhagenDenmark

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