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Evaluation of C26:0‐lysophosphatidylcholine and C26:0‐carnitine as diagnostic markers for Zellweger spectrum disorders
Author(s) -
Klouwer Femke C. C.,
Ferdinandusse Sacha,
Lenthe Henk,
Kulik Wim,
Wanders Ronald J. A.,
PollThe Bwee Tien,
Waterham Hans R.,
Vaz Frédéric M.
Publication year - 2017
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-017-0064-0
Subject(s) - carnitine , zellweger syndrome , lysophosphatidylcholine , medicine , endocrinology , biology , peroxisome , biochemistry , phosphatidylcholine , phospholipid , receptor , membrane
Zellweger spectrum disorders (ZSD) are a group of genetic metabolic disorders caused by a defect in peroxisome biogenesis. This results in multiple metabolic abnormalities, including elevated very long‐chain fatty acid (VLCFA) levels. Elevated levels of C26:0‐lysophosphatidylcholine (C26:0‐lysoPC) have been shown in dried blood spots (DBS) from ZSD patients. However, little is known about the sensitivity and specificity of this marker and C26:0‐carnitine, another VLCFA‐marker, in ZSD. We investigated C26:0‐lysoPC and C26:0‐carnitine as diagnostic markers for ZSD in DBS and fibroblasts. Methods C26:0‐lysoPC levels in 91 DBS from 37 different ZSD patients were determined and compared to the levels in 209 control DBS. C26:0‐carnitine levels were measured in 41 DBS from 29 ZSD patients and 97 control DBS. We measured C26:0‐lysoPC levels in fibroblasts from 24 ZSD patients and 61 control individuals. Results Elevated C26:0‐lysoPC levels (>72 nmol/L) were found in 86/91 ZSD DBS (n=33/37 patients) corresponding to a sensitivity of 89.2%. Median level was 567 nmol/l (range 28–3133 nmol/l). Consistently elevated C26:0‐carnitine levels (>0.077 μmol/L) in DBS were found in 16 out of 29 ZSD patients corresponding to a sensitivity of 55.2%. C26:0‐lysoPC levels were elevated in 21/24 ZSD fibroblast lines. Discussion C26:0‐lysoPC in DBS is a sensitive and useful marker for VLCFA accumulation in patients with a ZSD. C26:0‐carnitine in DBS is elevated in some ZSD patients, but is less useful as a diagnostic marker. Implementation of C26:0‐lysoPC measurement in the diagnostic work‐up when suspecting a ZSD is advised. This marker has the potential to be used for newborn screening for ZSD.