Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085584 (encephalopathy)
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Carnitine and its acylesters are a family of compounds that can be used in the early diagnosis of many diseases. Carnitine and acylcarnitines have a crucial role in fatty acid transportation. The increased level of free carnitine, total carnitine, or the acylesters can act as biomarkers for many metabolic disorders, including diabetes, encephalopathy and cardiomyopathy. The determination of these compounds is difficult owing to the simple aliphatic structure, the chiral center and the permanent positive charge. Although MS detection can be enough to differentiate between some carnitine derivatives, closely related structural isomers of the acylcarnitines must be separated before detection because they form the same base peak and second most abundant ion peak. Different separation methods are discussed in this review, including reversed-phase, hydrophilic interaction, ion exchange, ion pairing, mixed mode liquid chromatography, gas chromatography and electrophoresis. Representative example chromatograms are shown. The sample preparation and the different derivatization reactions are also covered. A table that summarizes the most important analytical methods by detailing the analyte mixture, the sample matrix, the separation mode and the detection method is provided.
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PMID:Separation of carnitine and acylcarnitines in biological samples: a review. 2400 2

Carnitine transporter defect (CTD; also known as systemic primary carnitine deficiency; MIM 212140) is due to mutations in the SLC22A5 gene and leads to extremely low carnitine levels in blood and tissues. Affected individuals may develop early onset cardiomyopathy, weakness, or encephalopathy, which may be serious or even fatal. The disorder can be suggested by newborn screening. However, markedly low newborn carnitine levels can also be caused by conditions unrelated to CTD, such as the low carnitine levels often associated with normal pregnancies and some metabolic disorders occurring in the mother. In order to clarify the biochemical characteristics most useful for identification of CTD in newborns, we examined California Department of Public Health newborn screening data for CTD from 2005 to 12 and performed detailed chart reviews at six metabolic centers in California. The reviews covered 14 cases of newborn CTD, 14 cases of maternal disorders (CTD, 6 cases; glutaric aciduria, type 1, 5; medium-chain acyl CoA dehydrogenase deficiency, 2; and cobalamin C deficiency, 1), and 154 false-positive cases identified by newborn screening. Our results show that newborns with CTD identified by NBS exhibit different biochemical characteristics, compared to individuals ascertained clinically. Newborns with CTD may have NBS dried blood spot free carnitine near the lower cutoff and confirmatory plasma total and free carnitine levels near the normal lower limit, particularly if obtained within two weeks after birth. These findings raise the concern that true cases of CTD may exist that could have been missed by newborn screening. CTD should be considered as a possible diagnosis in cases with suggestive clinical features, even if CTD was thought to be excluded in the newborn period. Maternal plasma total carnitine and newborn urine total carnitine values are the most important predictors of true CTD in newborns. However, biochemical testing alone does not yield a discriminant rule to distinguish true CTD from low carnitine in newborns due to other causes. Because of this biochemical variability and overlap, molecular genetic testing is imperative to confirm CTD in newborns. Additionally, functional testing of fibroblast carnitine uptake remains necessary for cases in which other confirmatory testing is inconclusive. Even with utilization of all available diagnostic testing methods, confirmation of CTD ascertained by NBS remains lengthy and challenging. Incorporation of molecular analysis as a second tier step in NBS for CTD may be beneficial and should be investigated.
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PMID:Biochemical characteristics of newborns with carnitine transporter defect identified by newborn screening in California. 2871 8


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