**8. Sengers Syndrome**

The clinical manifestation of Sengers syndrome is hypertrophic cardiomyopathy and congenital cataracts. Other symptoms including skeletal myopathy, exercise intolerance, lactic acidosis and 3-methylglutaconic aciduria, showing strong similarities to Barth syndrome [131] (Figure 5). Sengers syndrome is caused by mutations in the gene encoding for mitochondrial acylglycerol kinase (AGK) [132]. AGK is a mitochondrial lipid kinase strongly expressed in heart, but also in the skeletal muscle, kidney and brain. This protein can phosphorylate monoacylglycerol to lysophosphatidic acid (LPA) and diacylglycerol to phosphatidic acid (PA), a precursor of CL biosynthesis [132]. AGK has an additional independent function in mitochondrial protein import as a constituent of the mitochondrial carrier translocase TIM22 complex [81,133]. This inner membrane-embedded protein translocase imports proteins of the carrier family from the cytosol. Carrier proteins are a large family of proteins which mediate the transport of metabolites across the inner membrane. A defect in the import and assembly of carrier proteins has been found in AGK-deficient mitochondria [81,133]. In particular, decreased levels of mitochondrial ADP/ATP carrier in heart and muscle tissues was the initial finding in patients of Sengers syndrome [134]. The function in protein transport is independent of AGK kinase activity. It can be assumed that loss of both functions contributes to the pathogenesis in Sengers syndrome.
