HSD10 disease is caused by mutations in the HSD17B10 gene, which provides instructions for making the HSD10 protein. This protein is located within , the energy-producing centers inside cells, where it is involved in the . While most protein synthesis occurs in the fluid surrounding the nucleus (cytoplasm), a few proteins are synthesized in the mitochondria.
During protein synthesis, in either the mitochondria or the cytoplasm, molecules called (tRNAs) help assemble protein building blocks (amino acids) into chains that form proteins. The HSD10 protein is part of a group of proteins (a complex) that is involved in making functional mitochondrial tRNA molecules, which aid in the synthesis of mitochondrial proteins. Normal mitochondrial protein production is essential for the formation of the groups of proteins that convert the energy from food into a form cells can use.
The HSD17B10 gene mutations that cause HSD10 disease reduce the amount of HSD10 protein in cells, impair their structure or function, or both, which leads to a deficiency of the functional complex in which it plays a part. This deficiency impairs the production of mitochondrial tRNAs. Without enough tRNAs, the mitochondrial synthesis of proteins involved in cellular energy production is reduced. A shortage of these proteins results in insufficient energy production in cells of the brain, eyes, and heart, leading to the characteristic features of HSD10 disease.