FGF21 and GDF15 are elevated in Barth Syndrome and are correlated to important clinical measures.

Barth Syndrome (BTHS) is a rare X-linked disorder that is caused by defects TAFAZZIN, which leads to an abnormal cardiolipin (CL) profile of the inner mitochondrial membrane and clinical features including cardiomyopathy, neutropenia and skeletal myopathy. The ratio of monolysocardiolipin (MLCL, the remodeling intermediate of cardiolipin) to remodeled CL is always abnormal in Barth Syndrome and 3-methylglutaconic acid is often elevated affected patients, however neither of these biomarkers has been shown to temporally correlate to clinical status. In this study, we measured plasma FGF21 and GDF15 levels in 16 individuals with Barth Syndrome and evaluated whether these biomarkers were correlated to the MLCL/CL ratio in patient bloodspots and clinical laboratory parameters indicative of organ involvement in Barth Syndrome including: neutrophil and monocyte counts, liver function, and cardiac function (NT-proBNP). We found that FGF21 and GDF15 were elevated in all 16 patients and that FGF21 was significantly correlated to AST, ALT GGT, percentage of neutrophils comprising total white blood cells, percent monocytes comprising total white blood cells, and NT-proBNP levels. GDF-15 was significantly positively associated with NT-proBNP. We conclude that clinical measurements of FGF21 and GDF-15 may be relevant in the monitoring multi-organ system involvement in Barth Syndrome.

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Declaration of Competing Interest O.L. B.K.C. and C.M have no conflicts of interest to declare. H.J.V. has received research and clinical trial funding from Stealth BioTherapeutics, Needham, MA, USA.