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Title
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Fluxomic assay-assisted diagnosis orientation in a cohort of 11 patients with myopathic form of CPT2 deficiency
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Author
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Abstract
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| Carnitine palmitoyltransferase type 2 (CPT2) deficiency, a mitochondrial fatty acid oxidation disorder (MFAOD), is a cause of myopathy in its late clinical presentation. As for other MFAODs, its diagnosis may be evocated when blood acylcarnitine profile is abnormal. However, a lack of abnormalities or specificity in this profile is not exclusive of CPT2 deficiency. Our retrospective study reports clinical and biological data in a cohort of 11 patients with circulating acylcamitine profile unconclusive enough for a specific diagnosis orientation. In these patients, CPT2 gene studies was prompted by prior fluxomic explorations of mitochondrial beta-oxidation on intact whole blood cells incubated with pentadeuterated ([16-H-2(3), 15-H-2(2)])-palmitate. Clinical indication for fluxomic explorations was at least one acute rhabdomyolysis episode complicated, in 5 of 11 patients, by acute renal failure. Major trigger of rhabdomyolysis was febrile infection. In all patients, fluxomic data indicated deficient CPT2 function showing normal deuterated palmitoylcarnitine (C16-Cn) formation rates associated with increased ratios between generated C16-Cn and downstream deuterated metabolites (Sigma deuterated C2-Cn to C14-Cn). Subsequent gene studies showed in all patients pathogenic gene variants in either homozygous or compound heterozygous forms. Consistent with literature data, allelic frequency of the c.338C > T[p.Ser113Leu] mutation amounted to 68.2% in our cohort. Other missense mutations included c.149C > A[p.Pro50His] (9%), c.200C > G[p.A1a200Gly] (4.5%) and previously unreported c.1171A > G[p.ser391Gly] (4.5%) and c.1420G > C[p.Ala474Pro] (4.5%) mutations. Frameshift c.1666-1667delTT[p.Leu556val*16] mutation (9%) was observed in two patients unknown to be related. |
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Language
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English
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Source (journal)
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Molecular genetics and metabolism. - Orlando, Fla
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Publication
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Orlando, Fla
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2018
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ISSN
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1096-7192
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DOI
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10.1016/J.YMGME.2018.02.005
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Volume/pages
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123
:4
(2018)
, p. 441-448
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ISI
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000430037100005
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Pubmed ID
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29478820
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Full text (Publisher's DOI)
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