Quantitative and compositional study of cardiolipin in platelets by electrospray ionization mass spectrometry: application for the identification of Barth syndrome patients.
BACKGROUND
The concentration of cardiolipin (CL) in cultured skin fibroblasts is a useful indicator of Barth syndrome (BTHS; MIM 302060), but the sampling and culturing of fibroblasts are burdensome and time-consuming procedures. We investigated whether the analysis of CL in platelets might help to identify BTHS in patients suspected of having this condition.


METHODS
We used HPLC and online electrospray ionization mass spectrometry (HPLC-ESI-MS) to quantify CL molecular species. The CL content of platelets was studied in blood samples of BTHS and non-BTHS patients. Control blood samples drawn from healthy adults were collected and analyzed within 24 h (n = 10) and 48 h (n = 10) to characterize any effect of sample shipping time on the CL content in platelets. Samples were collected from children 1-10 years of age who were not affected by BTHS (n = 6) and from BTHS patients (n = 4) and analyzed within 24 h. Results for all four groups were compared by a Student t-test for all individual analyses.


RESULTS
We found different CL molecular species, e.g., (C18:2)(4)-CL. BTHS patients had a specific decrease of tetralinoleyl-CL concentrations in platelets (0.1-0.5 nmol/mg of protein; n = 4) compared with all control groups (2.3-5.5 nmol/mg of protein; n = 26). Only minor differences were observed among the different control groups.


CONCLUSIONS
Quantitative and compositional analyses of CL in platelets by the proposed method allow identification of BTHS patients more rapidly than gene analysis or analysis of CL in cultured skin fibroblasts. The abnormality of CL may explain the abnormal mitochondrial function observed in BTHS. The differences between the control groups did not cause any complication.
Academic Medical Center, University of Amsterdam, Laboratory Genetic Metabolic Diseases, Emma Children's Hospital, 1100 DE Amsterdam, The Netherlands.
Fredoen
F
Valianpour
Ronald J A
RJ
Wanders
Peter G
PG
Barth
Henk
H
Overmars
Albert H
AH
van Gennip
D000328:Adult; D001792:Blood Platelets / Q000737:chemistry*; D002308:Cardiolipins / Q000097:blood*; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis / Q000235:genetics*; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007223:Infant; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000235:genetics*; D009135:Muscular Diseases / Q000175:diagnosis / Q000235:genetics*; D009503:Neutropenia / Q000175:diagnosis / Q000235:genetics*; D021241:Spectrometry, Mass, Electrospray Ionization; D013577:Syndrome
D002308:Cardiolipins